Trial Outcomes & Findings for Cryoanalgesia to Treat Post-Amputation Phantom Limb Pain: A Department of Defense Funded Multicenter Study (NCT NCT03449667)

Last Updated: 2023-02-17

Results Overview

The difference in average daily phantom pain intensity at baseline and 4 months following the initial intervention (measured with the numeric rating scale as part of the Brief Pain Inventory with a minimum value of 0 and maximum value of 10, 0=no pain and 10=worst imaginable pain)

Recruitment status

COMPLETED

Study phase

Target enrollment

144 participants

Primary outcome timeframe

Baseline and 4 months later (difference between the two is the primary end point)

Results posted on

2023-02-17

Participant Flow

Participant milestones

Participant milestones
Measure	Cryoneurolysis, Then Optional Crossover Sham Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Cryoneurolysis: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Optional crossover: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Sham Comparator: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Optional crossover: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Initial Treatment STARTED	71	73
Initial Treatment COMPLETED	71	73
Initial Treatment NOT COMPLETED	0	0
Optional Crossover Treatment STARTED	71	73
Optional Crossover Treatment COMPLETED	42	49
Optional Crossover Treatment NOT COMPLETED	29	24

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cryoneurolysis, Then Optional Crossover Sham n=71 Participants Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Cryoneurolysis: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis n=73 Participants Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Sham Comparator: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Total n=144 Participants Total of all reporting groups
Age, Continuous	58 years STANDARD_DEVIATION 13 • n=71 Participants	58 years STANDARD_DEVIATION 13 • n=73 Participants	58 years STANDARD_DEVIATION 13 • n=144 Participants
Sex: Female, Male Female	18 Participants n=71 Participants	29 Participants n=73 Participants	47 Participants n=144 Participants
Sex: Female, Male Male	53 Participants n=71 Participants	44 Participants n=73 Participants	97 Participants n=144 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	71 participants n=71 Participants	73 participants n=73 Participants	144 participants n=144 Participants
Body mass index	29 kg/m^2 STANDARD_DEVIATION 5.8 • n=71 Participants	28 kg/m^2 STANDARD_DEVIATION 5.3 • n=73 Participants	28 kg/m^2 STANDARD_DEVIATION 5.5 • n=144 Participants
Marital status Single (never married)	16 Participants n=71 Participants	16 Participants n=73 Participants	32 Participants n=144 Participants
Marital status Single (divorced)	18 Participants n=71 Participants	12 Participants n=73 Participants	30 Participants n=144 Participants
Marital status Currently married	33 Participants n=71 Participants	36 Participants n=73 Participants	69 Participants n=144 Participants
Marital status Others (separated or widowed)	4 Participants n=71 Participants	9 Participants n=73 Participants	13 Participants n=144 Participants
Military Status Civilian (never in military)	59 Participants n=71 Participants	55 Participants n=73 Participants	114 Participants n=144 Participants
Military Status Veteran	11 Participants n=71 Participants	18 Participants n=73 Participants	29 Participants n=144 Participants
Military Status Active Duty	1 Participants n=71 Participants	0 Participants n=73 Participants	1 Participants n=144 Participants
Years of education	14 years n=71 Participants	14 years n=73 Participants	14 years n=144 Participants
Amputation Information Trans-femoral	22 Participants n=71 Participants	21 Participants n=73 Participants	43 Participants n=144 Participants
Amputation Information Trans-tibial	46 Participants n=71 Participants	46 Participants n=73 Participants	92 Participants n=144 Participants
Amputation Information Foot/ankle	3 Participants n=71 Participants	6 Participants n=73 Participants	9 Participants n=144 Participants
History of residual limb pain	55 Participants n=71 Participants	55 Participants n=73 Participants	110 Participants n=144 Participants
Current residual limb pain	44 Participants n=71 Participants	45 Participants n=73 Participants	89 Participants n=144 Participants
Current prosthesis use	66 Participants n=71 Participants	67 Participants n=73 Participants	133 Participants n=144 Participants
Distance of treatment from end of residual limb Sciatic nerve	15 cm n=71 Participants	17 cm n=73 Participants	16 cm n=144 Participants
Distance of treatment from end of residual limb Femoral nerve	22 cm n=71 Participants	22 cm n=73 Participants	22 cm n=144 Participants

PRIMARY outcome

Timeframe: Baseline and 4 months later (difference between the two is the primary end point)

Outcome measures

Outcome measures
Measure	Cryoneurolysis, Then Optional Crossover Sham n=71 Participants Initial treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Crossover treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis n=73 Participants Initial treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Crossover treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Change From Baseline in Average Daily Phantom Pain Intensity	0.5 score on a scale Interval -0.5 to 3.0	0 score on a scale Interval 0.0 to 3.0

SECONDARY outcome

Timeframe: Endpoints will be evaluated at baseline and on Days 1 and 7; and Months 1, 2, 3, and 4 after both the initial and subsequently the crossover treatments; and 12 months after the initial treatment

The average daily phantom pain intensity at between 1 day and 12 months following the initial intervention (measured with the numeric rating scale as part of the Brief Pain Inventory with a minimum value of 0 and maximum value of 10, 0=no pain and 10=worst imaginable pain) To read the results: for the group that received cryoneurolysis initially followed by sham for the crossover treatment, "initial" Days 1 - Month 4 provide the results for those receiving cryoneurolysis while "crossover" Days 1 - Month 4 provide the results for those receiving sham treatment. This is reversed for the other treatment group that received sham initially followed by cryoneurolysis for the crossover treatment.

Outcome measures

Outcome measures
Measure	Cryoneurolysis, Then Optional Crossover Sham n=71 Participants Initial treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Crossover treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis n=73 Participants Initial treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Crossover treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Average Daily Phantom Pain Intensity Day 0 (baseline)	5 score on a scale Interval 4.0 to 6.0	5 score on a scale Interval 4.0 to 7.0
Average Daily Phantom Pain Intensity Month 1, initial treatment	3.5 score on a scale Interval 0.0 to 5.0	4 score on a scale Interval 0.0 to 6.0
Average Daily Phantom Pain Intensity Month 2, initial treatment	3 score on a scale Interval 0.0 to 5.0	4 score on a scale Interval 2.0 to 5.0
Average Daily Phantom Pain Intensity Month 4, initial treatment	4.3 score on a scale Interval 1.5 to 6.0	4.5 score on a scale Interval 2.0 to 6.0
Average Daily Phantom Pain Intensity Day 0, crossover treatment	5 score on a scale Interval 3.0 to 7.0	5 score on a scale Interval 4.0 to 6.0
Average Daily Phantom Pain Intensity Month 1, crossover treatment	2 score on a scale Interval 0.0 to 4.0	3 score on a scale Interval 0.0 to 5.0
Average Daily Phantom Pain Intensity Month 2, crossover treatment	2 score on a scale Interval 0.0 to 4.0	3 score on a scale Interval 0.0 to 5.0
Average Daily Phantom Pain Intensity Month 3, crossover treatment	2 score on a scale Interval 0.0 to 4.0	3 score on a scale Interval 0.0 to 5.0
Average Daily Phantom Pain Intensity Day 1, initial treatment	0 score on a scale Interval 0.0 to 4.0	1 score on a scale Interval 0.0 to 5.0
Average Daily Phantom Pain Intensity Day 7, initial treatment	3 score on a scale Interval 0.0 to 5.0	3.5 score on a scale Interval 0.0 to 5.0
Average Daily Phantom Pain Intensity Month 3, initial treatment	3.5 score on a scale Interval 0.0 to 5.0	5 score on a scale Interval 2.0 to 6.0
Average Daily Phantom Pain Intensity Day 1, crossover treatment	0 score on a scale Interval 0.0 to 3.0	0 score on a scale Interval 0.0 to 2.5
Average Daily Phantom Pain Intensity Day 7, crossover treatment	0 score on a scale Interval 0.0 to 2.0	0 score on a scale Interval 0.0 to 5.0
Average Daily Phantom Pain Intensity Month 4, crossover treatment	2 score on a scale Interval 0.0 to 4.0	3.5 score on a scale Interval 0.0 to 5.0
Average Daily Phantom Pain Intensity Month 12, initial	1 score on a scale Interval 0.0 to 4.0	3 score on a scale Interval 0.0 to 5.0

SECONDARY outcome

The worst daily phantom pain intensity at between 1 day and 12 months following the initial intervention (measured with the numeric rating scale as part of the Brief Pain Inventory with a minimum value of 0 and maximum value of 10, 0=no pain and 10=worst imaginable pain). The worst pain is the maximum experienced in the previous 72 hour period (except day 1 which is the previous 24 hour period). To read the results: for the group that received cryoneurolysis initially followed by sham for the crossover treatment, "initial" Days 1 - Month 4 provide the results for those receiving cryoneurolysis while "crossover" Days 1 - Month 4 provide the results for those receiving sham treatment. This is reversed for the other treatment group that received sham initially followed by cryoneurolysis for the crossover treatment.

Outcome measures

Outcome measures
Measure	Cryoneurolysis, Then Optional Crossover Sham n=71 Participants Initial treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Crossover treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis n=73 Participants Initial treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Crossover treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Worst Daily Phantom Pain Intensity Month 1, initial treatment	6.5 score on a scale Interval 0.0 to 9.0	7 score on a scale Interval 0.0 to 9.0
Worst Daily Phantom Pain Intensity Month 3, initial treatment	7 score on a scale Interval 2.0 to 9.0	8 score on a scale Interval 5.0 to 9.0
Worst Daily Phantom Pain Intensity Day 1, crossover treatment	0 score on a scale Interval 0.0 to 5.0	0 score on a scale Interval 0.0 to 6.0
Worst Daily Phantom Pain Intensity Day 7, crossover treatment	0 score on a scale Interval 0.0 to 7.0	5.25 score on a scale Interval 0.0 to 8.5
Worst Daily Phantom Pain Intensity Month 1, crossover treatment	5 score on a scale Interval 0.0 to 8.0	6 score on a scale Interval 1.0 to 8.0
Worst Daily Phantom Pain Intensity Month 2, crossover treatment	6 score on a scale Interval 0.0 to 7.0	6 score on a scale Interval 3.0 to 7.5
Worst Daily Phantom Pain Intensity Month 3, crossover treatment	6 score on a scale Interval 0.0 to 8.0	7 score on a scale Interval 4.0 to 8.0
Worst Daily Phantom Pain Intensity Day 0 (baseline)	8 score on a scale Interval 7.0 to 9.0	8 score on a scale Interval 7.0 to 10.0
Worst Daily Phantom Pain Intensity Day 1, initial treatment	2.5 score on a scale Interval 0.0 to 7.0	3 score on a scale Interval 0.0 to 7.0
Worst Daily Phantom Pain Intensity Day 7, initial treatment	6 score on a scale Interval 0.0 to 8.5	6 score on a scale Interval 0.0 to 9.0
Worst Daily Phantom Pain Intensity Month 2, initial treatment	7 score on a scale Interval 1.0 to 9.0	7 score on a scale Interval 4.0 to 9.0
Worst Daily Phantom Pain Intensity Month 4, initial treatment	7.5 score on a scale Interval 4.0 to 9.0	8 score on a scale Interval 5.0 to 9.0
Worst Daily Phantom Pain Intensity Day 0, crossover treatment	8 score on a scale Interval 6.5 to 9.5	8 score on a scale Interval 6.0 to 9.0
Worst Daily Phantom Pain Intensity Month 4, crossover treatment	6 score on a scale Interval 0.0 to 8.0	6.5 score on a scale Interval 3.0 to 8.0
Worst Daily Phantom Pain Intensity Month 12, initial	6 score on a scale Interval 0.0 to 9.0	7 score on a scale Interval 3.0 to 8.0

SECONDARY outcome

Residual limb pain will be assessed using a Numeric Rating Scale which is a highly-sensitive measure of pain intensity with numbers ranging from 0 to 10, with zero equivalent to no pain and 10 equivalent to the worst imaginable pain. To read the results: for the group that received cryoneurolysis initially followed by sham for the crossover treatment, "initial" Days 1 - Month 4 provide the results for those receiving cryoneurolysis while "crossover" Days 1 - Month 4 provide the results for those receiving sham treatment. This is reversed for the other treatment group that received sham initially followed by cryoneurolysis for the crossover treatment.

Outcome measures

Outcome measures
Measure	Cryoneurolysis, Then Optional Crossover Sham n=71 Participants Initial treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Crossover treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis n=73 Participants Initial treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Crossover treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Residual Limb Pain, Average Month 4, initial treatment	0.5 score on a scale Interval 0.0 to 4.0	0.5 score on a scale Interval 0.0 to 4.5
Residual Limb Pain, Average Day 7, crossover treatment	0 score on a scale Interval 0.0 to 2.0	0 score on a scale Interval 0.0 to 3.0
Residual Limb Pain, Average Month 4, crossover treatment	0 score on a scale Interval 0.0 to 3.0	0 score on a scale Interval 0.0 to 4.0
Residual Limb Pain, Average Day 0 (baseline)	3 score on a scale Interval 0.0 to 6.0	3 score on a scale Interval 0.0 to 5.0
Residual Limb Pain, Average Day 1, initial treatment	0 score on a scale Interval 0.0 to 1.0	0 score on a scale Interval 0.0 to 2.0
Residual Limb Pain, Average Day 7, initial treatment	0 score on a scale Interval 0.0 to 4.0	0 score on a scale Interval 0.0 to 3.5
Residual Limb Pain, Average Month 1, initial treatment	0 score on a scale Interval 0.0 to 4.0	0 score on a scale Interval 0.0 to 3.5
Residual Limb Pain, Average Month 2, initial treatment	0 score on a scale Interval 0.0 to 3.5	0 score on a scale Interval 0.0 to 4.0
Residual Limb Pain, Average Month 3, initial treatment	0 score on a scale Interval 0.0 to 4.0	0 score on a scale Interval 0.0 to 4.0
Residual Limb Pain, Average Day 0, crossover treatment	3 score on a scale Interval 0.25 to 5.0	3 score on a scale Interval 0.0 to 6.0
Residual Limb Pain, Average Day 1, crossover treatment	0 score on a scale Interval 0.0 to 1.0	0 score on a scale Interval 0.0 to 0.0
Residual Limb Pain, Average Month 1, crossover treatment	0 score on a scale Interval 0.0 to 4.0	2 score on a scale Interval 0.0 to 4.0
Residual Limb Pain, Average Month 2, crossover treatment	0 score on a scale Interval 0.0 to 2.5	0 score on a scale Interval 0.0 to 4.0
Residual Limb Pain, Average Month 3, crossover treatment	0 score on a scale Interval 0.0 to 1.0	0 score on a scale Interval 0.0 to 5.0
Residual Limb Pain, Average Month 12, initial	0 score on a scale Interval 0.0 to 1.0	0 score on a scale Interval 0.0 to 3.0

SECONDARY outcome

Residual limb pain will be assessed using a Numeric Rating Scale which is a highly-sensitive measure of pain intensity with numbers ranging from 0 to 10, with zero equivalent to no pain and 10 equivalent to the worst imaginable pain. The worst pain is the maximum experienced over the previous 72 hours (24 hours for Day 1). To read the results: for the group that received cryoneurolysis initially followed by sham for the crossover treatment, "initial" Days 1 - Month 4 provide the results for those receiving cryoneurolysis while "crossover" Days 1 - Month 4 provide the results for those receiving sham treatment. This is reversed for the other treatment group that received sham initially followed by cryoneurolysis for the crossover treatment.

Outcome measures

Outcome measures
Measure	Cryoneurolysis, Then Optional Crossover Sham n=71 Participants Initial treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Crossover treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis n=73 Participants Initial treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Crossover treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Residual Limb Pain, Worst Month 4, crossover treatment	0 score on a scale Interval 0.0 to 7.0	2 score on a scale Interval 0.0 to 8.0
Residual Limb Pain, Worst Day 0 (baseline)	6 score on a scale Interval 0.0 to 8.0	5 score on a scale Interval 0.0 to 8.0
Residual Limb Pain, Worst Day 1, initial treatment	0 score on a scale Interval 0.0 to 5.0	0 score on a scale Interval 0.0 to 5.0
Residual Limb Pain, Worst Day 7, initial treatment	0 score on a scale Interval 0.0 to 6.0	0 score on a scale Interval 0.0 to 6.0
Residual Limb Pain, Worst Month 1, initial treatment	0 score on a scale Interval 0.0 to 7.0	1 score on a scale Interval 0.0 to 6.5
Residual Limb Pain, Worst Month 2, initial treatment	0 score on a scale Interval 0.0 to 6.0	0 score on a scale Interval 0.0 to 7.0
Residual Limb Pain, Worst Month 3, initial treatment	0 score on a scale Interval 0.0 to 7.0	0 score on a scale Interval 0.0 to 7.0
Residual Limb Pain, Worst Month 4, initial treatment	3 score on a scale Interval 0.0 to 8.0	2 score on a scale Interval 0.0 to 8.0
Residual Limb Pain, Worst Day 0, crossover treatment	6.5 score on a scale Interval 3.0 to 8.0	6 score on a scale Interval 0.0 to 8.0
Residual Limb Pain, Worst Day 1, crossover treatment	0 score on a scale Interval 0.0 to 2.0	0 score on a scale Interval 0.0 to 1.5
Residual Limb Pain, Worst Day 7, crossover treatment	0 score on a scale Interval 0.0 to 6.0	1.25 score on a scale Interval 0.0 to 7.0
Residual Limb Pain, Worst Month 1, crossover treatment	0 score on a scale Interval 0.0 to 8.0	5 score on a scale Interval 0.0 to 8.0
Residual Limb Pain, Worst Month 2, crossover treatment	0 score on a scale Interval 0.0 to 5.5	0 score on a scale Interval 0.0 to 7.0
Residual Limb Pain, Worst Month 3, crossover treatment	0 score on a scale Interval 0.0 to 6.0	0 score on a scale Interval 0.0 to 6.0
Residual Limb Pain, Worst Month 12, initial	0 score on a scale Interval 0.0 to 6.0	0 score on a scale Interval 0.0 to 7.0

SECONDARY outcome

Timeframe: Endpoints will be evaluated on Days 1 and 7; and Months 1, 2, 3, and 4 after both the initial and subsequently the crossover treatments; and 12 months after the initial treatment

The Patient Global Impression of Change Scale is a 7-point ordinal scale requiring the subject to rate the current severity of their global situation as it relates to phantom limb pain (as defined by each individual) compared to their baseline. This scale has the words "very much worse" to the left by the number one, and "very much improved" to the right, adjacent to the number seven. The words "no change" are in the middle of the scale above the number four. The Patient Global Impression of Change Scale has been validated in over ten prospective trials, including studies specifically involving peripheral neuropathy To read the results: for the group that received cryoneurolysis initially followed by sham for the crossover treatment, "initial" Days 1 - Month 4 provide the results for those receiving cryoneurolysis while "crossover" Days 1 - Month 4 provide the results for those receiving sham treatment. This is reversed for the other treatment group that received sham initially f

Outcome measures

Outcome measures
Measure	Cryoneurolysis, Then Optional Crossover Sham n=71 Participants Initial treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Crossover treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis n=73 Participants Initial treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Crossover treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Patient Global Impression of Change Month 1, initial treatment	4 score on a scale Interval 4.0 to 7.0	4 score on a scale Interval 4.0 to 7.0
Patient Global Impression of Change Month 12, initial	6 score on a scale Interval 4.0 to 7.0	5 score on a scale Interval 4.0 to 7.0
Patient Global Impression of Change Month 3, crossover treatment	6 score on a scale Interval 4.0 to 7.0	4 score on a scale Interval 4.0 to 7.0
Patient Global Impression of Change Day 1, initial treatment	7 score on a scale Interval 4.0 to 7.0	6 score on a scale Interval 4.0 to 7.0
Patient Global Impression of Change Day 7, initial treatment	5 score on a scale Interval 4.0 to 7.0	4 score on a scale Interval 4.0 to 7.0
Patient Global Impression of Change Month 2, initial treatment	4 score on a scale Interval 4.0 to 7.0	4 score on a scale Interval 4.0 to 6.0
Patient Global Impression of Change Month 3, initial treatment	4 score on a scale Interval 4.0 to 7.0	4 score on a scale Interval 4.0 to 5.0
Patient Global Impression of Change Month 4, initial treatment	4 score on a scale Interval 4.0 to 7.0	4 score on a scale Interval 4.0 to 6.0
Patient Global Impression of Change Day 1, crossover treatment	7 score on a scale Interval 6.0 to 7.0	7 score on a scale Interval 5.0 to 7.0
Patient Global Impression of Change Day 7, crossover treatment	7 score on a scale Interval 6.0 to 7.0	6 score on a scale Interval 4.0 to 7.0
Patient Global Impression of Change Month 1, crossover treatment	6 score on a scale Interval 4.0 to 7.0	4 score on a scale Interval 4.0 to 7.0
Patient Global Impression of Change Month 2, crossover treatment	6 score on a scale Interval 4.0 to 7.0	5 score on a scale Interval 4.0 to 7.0
Patient Global Impression of Change Month 4, crossover treatment	6 score on a scale Interval 4.0 to 7.0	4 score on a scale Interval 4.0 to 7.0

SECONDARY outcome

The Brief Pain Inventory (interference sub scale) is an instrument that measures the interference with physical and emotional functioning using a 0-10 scale (0 = no interference; 10 = complete interference). The seven interference questions involve general activity, mood, walking ability, normal work activities (both inside and outside of the home), relationships, sleep, and enjoyment of life. The seven functioning questions can be added to produce an interference subscale (0-70). A higher score reveals more interference with physical and emotional functioning. To read the results: for the group that received cryoneurolysis initially followed by sham for the crossover treatment, "initial" Days 1 - Month 4 provide the results for those receiving cryoneurolysis while "crossover" Days 1 - Month 4 provide the results for those receiving sham treatment. This is reversed for the other treatment group that received sham initially followed by cryoneurolysis for the crossover treatment.

Outcome measures

Outcome measures
Measure	Cryoneurolysis, Then Optional Crossover Sham n=71 Participants Initial treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Crossover treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis n=73 Participants Initial treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Crossover treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Brief Pain Inventory Interference Subscale Month 4, initial treatment	20 score on a scale Interval 0.0 to 38.0	19 score on a scale Interval 4.0 to 32.0
Brief Pain Inventory Interference Subscale Month 1, crossover treatment	4 score on a scale Interval 0.0 to 28.0	12 score on a scale Interval 0.0 to 31.0
Brief Pain Inventory Interference Subscale Month 2, crossover treatment	10 score on a scale Interval 0.0 to 21.5	14 score on a scale Interval 0.0 to 35.0
Brief Pain Inventory Interference Subscale Day 0 (baseline)	36 score on a scale Interval 21.0 to 47.0	34 score on a scale Interval 22.0 to 43.0
Brief Pain Inventory Interference Subscale Day 1, initial treatment	0 score on a scale Interval 0.0 to 22.0	0 score on a scale Interval 0.0 to 19.0
Brief Pain Inventory Interference Subscale Day 7, initial treatment	7 score on a scale Interval 0.0 to 32.0	19 score on a scale Interval 0.0 to 34.0
Brief Pain Inventory Interference Subscale Month 1, initial treatment	15 score on a scale Interval 0.0 to 40.0	22 score on a scale Interval 2.0 to 33.0
Brief Pain Inventory Interference Subscale Month 2, initial treatment	10 score on a scale Interval 0.0 to 40.0	22 score on a scale Interval 2.0 to 35.0
Brief Pain Inventory Interference Subscale Month 3, initial treatment	13 score on a scale Interval 0.0 to 38.0	21 score on a scale Interval 5.0 to 38.0
Brief Pain Inventory Interference Subscale Day 0, crossover treatment	26 score on a scale Interval 10.0 to 42.0	27 score on a scale Interval 20.0 to 39.0
Brief Pain Inventory Interference Subscale Day 1, crossover treatment	0 score on a scale Interval 0.0 to 7.0	0 score on a scale Interval 0.0 to 7.0
Brief Pain Inventory Interference Subscale Day 7, crossover treatment	0 score on a scale Interval 0.0 to 14.0	2 score on a scale Interval 0.0 to 32.0
Brief Pain Inventory Interference Subscale Month 3, crossover treatment	9 score on a scale Interval 0.0 to 22.0	18 score on a scale Interval 0.0 to 31.0
Brief Pain Inventory Interference Subscale Month 4, crossover treatment	11 score on a scale Interval 0.0 to 24.0	17 score on a scale Interval 0.0 to 34.0
Brief Pain Inventory Interference Subscale Month 12, initial	14 score on a scale Interval 4.0 to 33.0	12 score on a scale Interval 2.0 to 35.0

SECONDARY outcome

Timeframe: At baseline, 4 months after the initial and crossover treatments as well as 12 months after the initial treatment

The Beck Depression Inventory is a 21-item instrument that measures characteristic symptoms and signs of depression, requires only a 5th grade comprehension level to adequately understand the questions, and demonstrates a high internal consistency (0.73-0.92, mean of 0.86), reliability and validity. Each of the 21 factors is rated on a 0-3 scale, and then summed to produce the total score of 0-63. Mild, moderate, and severe depression is defined with scores of 10-18, 19-29, and 30-63, respectively. To read the results: for the group that received cryoneurolysis initially followed by sham for the crossover treatment, "initial" Month 4 provides the results for those receiving cryoneurolysis while "crossover" Month 4 provides the results for those receiving sham treatment. This is reversed for the other treatment group that received sham initially followed by cryoneurolysis for the crossover treatment.

Outcome measures

Outcome measures
Measure	Cryoneurolysis, Then Optional Crossover Sham n=71 Participants Initial treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Crossover treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis n=73 Participants Initial treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Crossover treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Beck Depression Inventory Month 4, initial treatment	4 score on a scale Interval 0.0 to 14.0	2 score on a scale Interval 0.0 to 9.0
Beck Depression Inventory Baseline (Day 0)	10 score on a scale Interval 5.0 to 17.0	9 score on a scale Interval 4.0 to 13.0
Beck Depression Inventory Month 4, crossover treatment	0 score on a scale Interval 0.0 to 5.0	0 score on a scale Interval 0.0 to 6.0
Beck Depression Inventory Month 12, initial	0 score on a scale Interval 0.0 to 7.0	0 score on a scale Interval 0.0 to 3.0

SECONDARY outcome

Pain perceived to emanate from part of the injured limb that no longer exists. The frequency is the number of times this is experienced in the previous 72 hours. To read the results: for the group that received cryoneurolysis initially followed by sham for the crossover treatment, "initial" Days 1 - Month 4 provide the results for those receiving cryoneurolysis while "crossover" Days 1 - Month 4 provide the results for those receiving sham treatment. This is reversed for the other treatment group that received sham initially followed by cryoneurolysis for the crossover treatment.

Outcome measures

Outcome measures
Measure	Cryoneurolysis, Then Optional Crossover Sham n=71 Participants Initial treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Crossover treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis n=73 Participants Initial treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Crossover treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Phantom Limb Pain Frequency Day 1, initial treatment	1 Occurrences Interval 0.0 to 24.0	2 Occurrences Interval 0.0 to 24.0
Phantom Limb Pain Frequency Day 7, initial treatment	9 Occurrences Interval 0.0 to 24.0	24 Occurrences Interval 2.0 to 24.0
Phantom Limb Pain Frequency Baseline (Day 0)	24 Occurrences Interval 12.0 to 24.0	24 Occurrences Interval 16.0 to 24.0
Phantom Limb Pain Frequency Month 1, initial treatment	11 Occurrences Interval 1.0 to 24.0	24 Occurrences Interval 1.0 to 24.0
Phantom Limb Pain Frequency Month 2, initial treatment	15 Occurrences Interval 1.0 to 24.0	24 Occurrences Interval 3.0 to 24.0
Phantom Limb Pain Frequency Month 3, initial treatment	24 Occurrences Interval 1.0 to 24.0	24 Occurrences Interval 5.0 to 24.0
Phantom Limb Pain Frequency Month 4, initial treatment	24 Occurrences Interval 2.0 to 24.0	24 Occurrences Interval 4.0 to 24.0
Phantom Limb Pain Frequency Day 0, crossover treatment	22 Occurrences Interval 4.0 to 24.0	24 Occurrences Interval 5.0 to 24.0
Phantom Limb Pain Frequency Day 1, crossover treatment	0 Occurrences Interval 0.0 to 24.0	0 Occurrences Interval 0.0 to 24.0
Phantom Limb Pain Frequency Day 7, crossover treatment	0 Occurrences Interval 0.0 to 20.0	4.5 Occurrences Interval 0.0 to 24.0
Phantom Limb Pain Frequency Month 1, crossover treatment	4 Occurrences Interval 0.0 to 24.0	12 Occurrences Interval 1.0 to 24.0
Phantom Limb Pain Frequency Month 2, crossover treatment	3 Occurrences Interval 0.0 to 24.0	15 Occurrences Interval 1.0 to 24.0
Phantom Limb Pain Frequency Month 3, crossover treatment	7.5 Occurrences Interval 0.0 to 24.0	9 Occurrences Interval 3.0 to 24.0
Phantom Limb Pain Frequency Month 4, crossover treatment	8 Occurrences Interval 0.0 to 24.0	24 Occurrences Interval 2.0 to 24.0
Phantom Limb Pain Frequency Month 12, initial	3 Occurrences Interval 0.0 to 24.0	4 Occurrences Interval 1.0 to 24.0

SECONDARY outcome

Pain perceived to emanate from part of the injured limb that no longer exists. The duration is the average number of hours that each occurrence is experienced in the previous 72 hours. To read the results: for the group that received cryoneurolysis initially followed by sham for the crossover treatment, "initial" Days 1 - Month 4 provide the results for those receiving cryoneurolysis while "crossover" Days 1 - Month 4 provide the results for those receiving sham treatment. This is reversed for the other treatment group that received sham initially followed by cryoneurolysis for the crossover treatment.

Outcome measures

Outcome measures
Measure	Cryoneurolysis, Then Optional Crossover Sham n=71 Participants Initial treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Crossover treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis n=73 Participants Initial treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Crossover treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Phantom Limb Pain Duration Month 2, initial treatment	2 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0
Phantom Limb Pain Duration Month 4, initial treatment	15 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0
Phantom Limb Pain Duration Baseline (Day 0)	24 hours Interval 1.0 to 24.0	24 hours Interval 2.0 to 24.0
Phantom Limb Pain Duration Day 1, initial treatment	0 hours Interval 0.0 to 24.0	0 hours Interval 0.0 to 24.0
Phantom Limb Pain Duration Day 7, initial treatment	0 hours Interval 0.0 to 24.0	3 hours Interval 0.0 to 24.0
Phantom Limb Pain Duration Month 1, initial treatment	1 hours Interval 0.0 to 24.0	2 hours Interval 0.0 to 24.0
Phantom Limb Pain Duration Month 3, initial treatment	24 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0
Phantom Limb Pain Duration Day 0, crossover treatment	13.5 hours Interval 0.0 to 24.0	24 hours Interval 0.2 to 24.0
Phantom Limb Pain Duration Day 1, crossover treatment	0 hours Interval 0.0 to 1.0	0 hours Interval 0.0 to 24.0
Phantom Limb Pain Duration Day 7, crossover treatment	0 hours Interval 0.0 to 1.0	1 hours Interval 0.0 to 24.0
Phantom Limb Pain Duration Month 1, crossover treatment	0.1 hours Interval 0.0 to 24.0	3 hours Interval 0.0 to 24.0
Phantom Limb Pain Duration Month 2, crossover treatment	1 hours Interval 0.0 to 24.0	1 hours Interval 0.0 to 24.0
Phantom Limb Pain Duration Month 3, crossover treatment	0 hours Interval 0.0 to 24.0	10 hours Interval 0.0 to 24.0
Phantom Limb Pain Duration Month 4, crossover treatment	0.2 hours Interval 0.0 to 24.0	24 hours Interval 0.1 to 24.0
Phantom Limb Pain Duration Month 12, initial	1 hours Interval 0.0 to 24.0	1 hours Interval 0.0 to 24.0

SECONDARY outcome

Sensations that feel to emanate from the missing limb, but are not described as pain. The frequency is the number of times this is experienced in the previous 72 hours. To read the results: for the group that received cryoneurolysis initially followed by sham for the crossover treatment, "initial" Days 1 - Month 4 provide the results for those receiving cryoneurolysis while "crossover" Days 1 - Month 4 provide the results for those receiving sham treatment. This is reversed for the other treatment group that received sham initially followed by cryoneurolysis for the crossover treatment.

Outcome measures

Outcome measures
Measure	Cryoneurolysis, Then Optional Crossover Sham n=71 Participants Initial treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Crossover treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis n=73 Participants Initial treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Crossover treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Non-painful Phantom Sensations Frequency Month 1, initial treatment	12 Occurrences Interval 0.0 to 24.0	24 Occurrences Interval 0.0 to 24.0
Non-painful Phantom Sensations Frequency Baseline (Day 0)	24 Occurrences Interval 5.0 to 24.0	24 Occurrences Interval 4.0 to 24.0
Non-painful Phantom Sensations Frequency Day 1, initial treatment	0 Occurrences Interval 0.0 to 24.0	1 Occurrences Interval 0.0 to 24.0
Non-painful Phantom Sensations Frequency Day 7, initial treatment	9 Occurrences Interval 0.0 to 24.0	24 Occurrences Interval 0.0 to 24.0
Non-painful Phantom Sensations Frequency Month 2, initial treatment	10 Occurrences Interval 0.0 to 24.0	24 Occurrences Interval 0.0 to 24.0
Non-painful Phantom Sensations Frequency Month 3, initial treatment	24 Occurrences Interval 0.0 to 24.0	24 Occurrences Interval 0.0 to 24.0
Non-painful Phantom Sensations Frequency Month 4, initial treatment	24 Occurrences Interval 0.0 to 24.0	24 Occurrences Interval 0.0 to 24.0
Non-painful Phantom Sensations Frequency Day 0, crossover treatment	24 Occurrences Interval 2.0 to 24.0	24 Occurrences Interval 5.0 to 24.0
Non-painful Phantom Sensations Frequency Day 1, crossover treatment	0 Occurrences Interval 0.0 to 24.0	0 Occurrences Interval 0.0 to 24.0
Non-painful Phantom Sensations Frequency Day 7, crossover treatment	0 Occurrences Interval 0.0 to 24.0	0 Occurrences Interval 0.0 to 24.0
Non-painful Phantom Sensations Frequency Month 1, crossover treatment	2 Occurrences Interval 0.0 to 24.0	24 Occurrences Interval 0.0 to 24.0
Non-painful Phantom Sensations Frequency Month 2, crossover treatment	14 Occurrences Interval 0.0 to 24.0	0 Occurrences Interval 0.0 to 24.0
Non-painful Phantom Sensations Frequency Month 3, crossover treatment	2 Occurrences Interval 0.0 to 24.0	24 Occurrences Interval 0.0 to 24.0
Non-painful Phantom Sensations Frequency Month 4, crossover treatment	3 Occurrences Interval 0.0 to 24.0	24 Occurrences Interval 0.0 to 24.0
Non-painful Phantom Sensations Frequency Month 12, initial	0 Occurrences Interval 0.0 to 24.0	0 Occurrences Interval 0.0 to 24.0

SECONDARY outcome

Sensations that feel to emanate from the missing limb, but are not described as pain. The duration is the average duration of each experience over the previous 72 hours. To read the results: for the group that received cryoneurolysis initially followed by sham for the crossover treatment, "initial" Days 1 - Month 4 provide the results for those receiving cryoneurolysis while "crossover" Days 1 - Month 4 provide the results for those receiving sham treatment. This is reversed for the other treatment group that received sham initially followed by cryoneurolysis for the crossover treatment.

Outcome measures

Outcome measures
Measure	Cryoneurolysis, Then Optional Crossover Sham n=71 Participants Initial treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Crossover treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis n=73 Participants Initial treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Crossover treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Non-painful Phantom Sensations Duration Baseline (Day 0)	24 hours Interval 1.0 to 24.0	24 hours Interval 0.0 to 24.0
Non-painful Phantom Sensations Duration Day 1, initial treatment	0 hours Interval 0.0 to 24.0	0 hours Interval 0.0 to 24.0
Non-painful Phantom Sensations Duration Day 7, initial treatment	1 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0
Non-painful Phantom Sensations Duration Month 1, initial treatment	2 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0
Non-painful Phantom Sensations Duration Month 2, initial treatment	2 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0
Non-painful Phantom Sensations Duration Month 3, initial treatment	24 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0
Non-painful Phantom Sensations Duration Month 4, initial treatment	24 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0
Non-painful Phantom Sensations Duration Day 0, crossover treatment	24 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0
Non-painful Phantom Sensations Duration Day 1, crossover treatment	0 hours Interval 0.0 to 24.0	0 hours Interval 0.0 to 24.0
Non-painful Phantom Sensations Duration Day 7, crossover treatment	0 hours Interval 0.0 to 24.0	0 hours Interval 0.0 to 24.0
Non-painful Phantom Sensations Duration 0Month 1, crossover treatment	0 hours Interval 0.0 to 24.0	0 hours Interval 0.0 to 24.0
Non-painful Phantom Sensations Duration Month 2, crossover treatment	12.5 hours Interval 0.0 to 24.0	0 hours Interval 0.0 to 24.0
Non-painful Phantom Sensations Duration Month 3, crossover treatment	2 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0
Non-painful Phantom Sensations Duration Month 4, crossover treatment	2 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0
Non-painful Phantom Sensations Duration Month 12, initial	0 hours Interval 0.0 to 24.0	0 hours Interval 0.0 to 24.0

SECONDARY outcome

Pain that originates from a part of the injured limb that remains intact. The frequency is the number of times residual pain is experienced in the previous 72 hours. To read the results: for the group that received cryoneurolysis initially followed by sham for the crossover treatment, "initial" Days 1 - Month 4 provide the results for those receiving cryoneurolysis while "crossover" Days 1 - Month 4 provide the results for those receiving sham treatment. This is reversed for the other treatment group that received sham initially followed by cryoneurolysis for the crossover treatment.

Outcome measures

Outcome measures
Measure	Cryoneurolysis, Then Optional Crossover Sham n=71 Participants Initial treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Crossover treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis n=73 Participants Initial treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Crossover treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Residual Limb Pain Frequency Baseline (Day 0)	5 Occurrences Interval 0.0 to 24.0	12 Occurrences Interval 0.0 to 24.0
Residual Limb Pain Frequency Day 1, initial treatment	0 Occurrences Interval 0.0 to 20.0	0 Occurrences Interval 0.0 to 6.0
Residual Limb Pain Frequency Day 7, initial treatment	0 Occurrences Interval 0.0 to 24.0	0 Occurrences Interval 0.0 to 24.0
Residual Limb Pain Frequency Month 1, initial treatment	0 Occurrences Interval 0.0 to 24.0	0 Occurrences Interval 0.0 to 24.0
Residual Limb Pain Frequency Month 2, initial treatment	0 Occurrences Interval 0.0 to 24.0	0 Occurrences Interval 0.0 to 24.0
Residual Limb Pain Frequency Month 3, initial treatment	0 Occurrences Interval 0.0 to 24.0	0 Occurrences Interval 0.0 to 24.0
Residual Limb Pain Frequency Month 4, initial treatment	2 Occurrences Interval 0.0 to 24.0	3 Occurrences Interval 0.0 to 24.0
Residual Limb Pain Frequency Day 0, crossover treatment	3.5 Occurrences Interval 1.0 to 24.0	6 Occurrences Interval 0.0 to 24.0
Residual Limb Pain Frequency Day 1, crossover treatment	0 Occurrences Interval 0.0 to 3.0	0 Occurrences Interval 0.0 to 0.5
Residual Limb Pain Frequency Day 7, crossover treatment	0 Occurrences Interval 0.0 to 24.0	0 Occurrences Interval 0.0 to 24.0
Residual Limb Pain Frequency Month 1, crossover treatment	1 Occurrences Interval 0.0 to 24.0	3 Occurrences Interval 0.0 to 24.0
Residual Limb Pain Frequency Month 2, crossover treatment	0 Occurrences Interval 0.0 to 24.0	3 Occurrences Interval 0.0 to 24.0
Residual Limb Pain Frequency Month 3, crossover treatment	0 Occurrences Interval 0.0 to 2.0	0 Occurrences Interval 0.0 to 24.0
Residual Limb Pain Frequency Month 4, crossover treatment	0 Occurrences Interval 0.0 to 21.0	1 Occurrences Interval 0.0 to 24.0
Residual Limb Pain Frequency Month 12, initial	0 Occurrences Interval 0.0 to 6.0	0 Occurrences Interval 0.0 to 24.0

SECONDARY outcome

Pain that originates from a part of the injured limb that remains intact. The duration is the average number of hours that residual pain was experienced each episode in the previous 72 hours. To read the results: for the group that received cryoneurolysis initially followed by sham for the crossover treatment, "initial" Days 1 - Month 4 provide the results for those receiving cryoneurolysis while "crossover" Days 1 - Month 4 provide the results for those receiving sham treatment. This is reversed for the other treatment group that received sham initially followed by cryoneurolysis for the crossover treatment.

Outcome measures

Outcome measures
Measure	Cryoneurolysis, Then Optional Crossover Sham n=71 Participants Initial treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Crossover treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.	Sham, Then Optional Crossover Cryoneurolysis n=73 Participants Initial treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Crossover treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Residual Limb Pain Duration Month 12, initial	1 hours Interval 0.0 to 24.0	24 hours Interval 1.0 to 24.0
Residual Limb Pain Duration Month 4, crossover treatment	0.8 hours Interval 0.0 to 24.0	24 hours Interval 1.0 to 24.0
Residual Limb Pain Duration Baseline (Day 0)	24 hours Interval 2.0 to 24.0	24 hours Interval 1.0 to 24.0
Residual Limb Pain Duration Day 1, initial treatment	1 hours Interval 0.0 to 24.0	15 hours Interval 0.0 to 24.0
Residual Limb Pain Duration Day 7, initial treatment	1 hours Interval 0.0 to 24.0	15 hours Interval 0.0 to 24.0
Residual Limb Pain Duration Month 1, initial treatment	2 hours Interval 0.0 to 24.0	1 hours Interval 0.0 to 24.0
Residual Limb Pain Duration Month 2, initial treatment	12 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0
Residual Limb Pain Duration Month 3, initial treatment	1 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0
Residual Limb Pain Duration Month 4, initial treatment	24 hours Interval 0.0 to 24.0	24 hours Interval 1.0 to 24.0
Residual Limb Pain Duration Day 0, crossover treatment	3 hours Interval 0.0 to 24.0	4.5 hours Interval 0.5 to 24.0
Residual Limb Pain Duration Day 1, crossover treatment	0 hours Interval 0.0 to 24.0	0.5 hours Interval 0.0 to 24.0
Residual Limb Pain Duration Day 7, crossover treatment	0 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0
Residual Limb Pain Duration Month 1, crossover treatment	0.3 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0
Residual Limb Pain Duration Month 2, crossover treatment	0.1 hours Interval 0.0 to 24.0	24 hours Interval 1.0 to 24.0
Residual Limb Pain Duration Month 3, crossover treatment	0 hours Interval 0.0 to 24.0	24 hours Interval 0.0 to 24.0

Adverse Events

Cryoneurolysis

Serious events: 1 serious events

Other events: 0 other events

Deaths: 1 deaths

Sham Comparator

Serious events: 1 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Cryoneurolysis n=120 participants at risk Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Cryoneurolysis: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.	Sham Comparator n=115 participants at risk Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Sham Comparator: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.
Nervous system disorders Dementia of unknown origin	0.00% 0/120 • 1 year	0.87% 1/115 • Number of events 1 • 1 year
Musculoskeletal and connective tissue disorders fall	0.83% 1/120 • Number of events 1 • 1 year	0.00% 0/115 • 1 year

Other adverse events

Adverse event data not reported

Additional Information

Brian M. Ilfeld, MD, MS

University of California San Diego

Phone: (858) 822-0776

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place