Trial Outcomes & Findings for Effect of Auricular Vagal Nerve Electrical Stimulation on Post-Treatment Lyme Disease Syndrome (NCT NCT04938687)
NCT ID: NCT04938687
Last Updated: 2026-02-12
Results Overview
This 55-item questionnaire evaluates the frequency, severity, and incidence of Lyme symptoms as well as assessing one's perceived overall health. Minimum value:0 Maximum value: 114 The higher number indicates more symptoms
Recruitment status
COMPLETED
Target enrollment
15 participants
Primary outcome timeframe
Before treatment (baseline) and Post treatment ( at the end of 2-week treatment)
Results posted on
2026-02-12
Participant Flow
Participant milestones
| Measure |
RAVANS
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
7
|
|
Overall Study
COMPLETED
|
8
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of Auricular Vagal Nerve Electrical Stimulation on Post-Treatment Lyme Disease Syndrome
Baseline characteristics by cohort
| Measure |
RAVANS
n=8 Participants
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
n=7 Participants
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
Total
n=15 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.3 years
STANDARD_DEVIATION 18.1 • n=41 Participants
|
59.1 years
STANDARD_DEVIATION 12.6 • n=1581 Participants
|
54.4 years
STANDARD_DEVIATION 15.9 • n=4626 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=41 Participants
|
5 Participants
n=1581 Participants
|
11 Participants
n=4626 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=41 Participants
|
2 Participants
n=1581 Participants
|
4 Participants
n=4626 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=41 Participants
|
7 Participants
n=1581 Participants
|
15 Participants
n=4626 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=41 Participants
|
7 Participants
n=1581 Participants
|
15 Participants
n=4626 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=41 Participants
|
7 participants
n=1581 Participants
|
15 participants
n=4626 Participants
|
|
Functional Comorbidity Index
|
15.1 units on a scale
STANDARD_DEVIATION 1.21 • n=41 Participants
|
14.6 units on a scale
STANDARD_DEVIATION 2.4 • n=1581 Participants
|
14.8 units on a scale
STANDARD_DEVIATION 1.9 • n=4626 Participants
|
PRIMARY outcome
Timeframe: Before treatment (baseline) and Post treatment ( at the end of 2-week treatment)This 55-item questionnaire evaluates the frequency, severity, and incidence of Lyme symptoms as well as assessing one's perceived overall health. Minimum value:0 Maximum value: 114 The higher number indicates more symptoms
Outcome measures
| Measure |
RAVANS
n=8 Participants
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
n=7 Participants
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
|---|---|---|
|
Horowitz Lyme-Multiple Systemic Infectious Disease Syndrome Questionnaire
Before Treatment
|
50.5 score on a scale
Standard Deviation 21.3
|
44.8 score on a scale
Standard Deviation 14.1
|
|
Horowitz Lyme-Multiple Systemic Infectious Disease Syndrome Questionnaire
Post Treatment
|
33.8 score on a scale
Standard Deviation 17.3
|
25.6 score on a scale
Standard Deviation 9.9
|
SECONDARY outcome
Timeframe: Before treatment (baseline) and Post treatment (at the end of 2-week treatment)This 18-item questionnaire asks about the amount of time spent engaged in sedentary behaviors on typical weekdays and weekends. Minimum:0 Maximum:162 The higher scores mean higher sedentary behaviors
Outcome measures
| Measure |
RAVANS
n=8 Participants
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
n=7 Participants
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
|---|---|---|
|
Sedentary Behaviors Questionnaire
Before Treatment
|
55.8 score on a scale
Standard Deviation 11.5
|
49.5 score on a scale
Standard Deviation 8.4
|
|
Sedentary Behaviors Questionnaire
Post Treatment
|
48.8 score on a scale
Standard Deviation 22.5
|
52.6 score on a scale
Standard Deviation 12.4
|
SECONDARY outcome
Timeframe: Before treatment (baseline) and Post treatment (at the end of 2-week treatment)This non-diagnosis-specific questionnaire measures the severity of fatigue symptoms and how much these factors interfere with the subjects' lives. Minimum value:0 Maximum value:127 The higher scores mean higher fatigue symptoms
Outcome measures
| Measure |
RAVANS
n=8 Participants
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
n=7 Participants
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
|---|---|---|
|
Fatigue Symptom Inventory
Before Treatment
|
89.4 score on a scale
Standard Deviation 20.6
|
65.4 score on a scale
Standard Deviation 34.3
|
|
Fatigue Symptom Inventory
Post Treatment
|
66.8 score on a scale
Standard Deviation 31.4
|
44.3 score on a scale
Standard Deviation 22.9
|
SECONDARY outcome
Timeframe: Before treatment (baseline) and Post treatment (at the end of 2-week treatment)This 15-item questionnaire assesses the location, severity, and type of current pain, using analogue scales and body diagrams. Subscale-pain 24 hours describes the pain at its worst in the past 24 hours. Minimum value:0 Maximum value: 10 The higher scores means higher pain level
Outcome measures
| Measure |
RAVANS
n=8 Participants
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
n=7 Participants
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
|---|---|---|
|
Brief Pain Inventory-Pain 24 Hours
Before Treatment
|
5.6 score on a scale
Standard Deviation 2.1
|
6.4 score on a scale
Standard Deviation 2.2
|
|
Brief Pain Inventory-Pain 24 Hours
Post Treatment
|
4.8 score on a scale
Standard Deviation 3.3
|
4.4 score on a scale
Standard Deviation 2.9
|
SECONDARY outcome
Timeframe: Before treatment (baseline) and Post treatment (at the end of 2-week treatment)This questionnaire evaluates current depressive symptoms. Minimum value: 0 Maximum value: 63 The higher scores mean higher depressive symptoms
Outcome measures
| Measure |
RAVANS
n=8 Participants
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
n=7 Participants
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
|---|---|---|
|
Beck Depression Inventory
Post Treatment
|
33.7 score on a scale
Standard Deviation 14.6
|
28 score on a scale
Standard Deviation 4.9
|
|
Beck Depression Inventory
Before Treatment
|
42.1 score on a scale
Standard Deviation 12.9
|
33.3 score on a scale
Standard Deviation 10.9
|
SECONDARY outcome
Timeframe: Before treatment (at baseline) and after treatment (at the end of 2-week treatment)This questionnaire evaluates current anxiety symptoms. Minimum value: 0 Maximum value: 63 The higher scores mean higher anxiety symptoms
Outcome measures
| Measure |
RAVANS
n=8 Participants
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
n=7 Participants
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
|---|---|---|
|
Beck Anxiety Inventory
Before Treatment
|
19.5 score on a scale
Standard Deviation 11.1
|
13.1 score on a scale
Standard Deviation 0.8
|
|
Beck Anxiety Inventory
Post Treatment
|
11.5 score on a scale
Standard Deviation 9.9
|
9.3 score on a scale
Standard Deviation 6.2
|
SECONDARY outcome
Timeframe: Before treatment (baseline) and Post treatment (at the end of 2-week treatment)This 9-item questionnaire assesses sleep quality and patterns of sleep. Minimum value: 0 Maximum value: 21 The higher scores mean poorer sleep quality
Outcome measures
| Measure |
RAVANS
n=8 Participants
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
n=7 Participants
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
|---|---|---|
|
Pittsburgh Sleep Quality Index
Before Treatment
|
13.8 score on a scale
Standard Deviation 4.2
|
9.0 score on a scale
Standard Deviation 4.2
|
|
Pittsburgh Sleep Quality Index
Post Treatment
|
9.8 score on a scale
Standard Deviation 5.7
|
8.0 score on a scale
Standard Deviation 3.9
|
SECONDARY outcome
Timeframe: Before treatment ( baseline) and Post treatment (at the end of 2-week treatment)Measures the time it takes for a person to stand up from a chair, walk 3 meter, turn, walk back, and sit down again.
Outcome measures
| Measure |
RAVANS
n=8 Participants
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
n=7 Participants
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
|---|---|---|
|
Timed Up and Go
Post Treatment
|
9.5 seconds
Standard Deviation 2.8
|
8.6 seconds
Standard Deviation 1.7
|
|
Timed Up and Go
Before Treatment
|
10.5 seconds
Standard Deviation 3.5
|
9.3 seconds
Standard Deviation 2.4
|
SECONDARY outcome
Timeframe: Before treatment (baseline) and Post treatment (at the end of 2-week treatment)Measure usual walk speed
Outcome measures
| Measure |
RAVANS
n=8 Participants
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
n=7 Participants
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
|---|---|---|
|
Time to Complete 4 Meters at Usual Walking Speed,
Post Treatment
|
4.2 seconds
Standard Deviation 0.9
|
4.3 seconds
Standard Deviation 1.0
|
|
Time to Complete 4 Meters at Usual Walking Speed,
Before Treatment
|
4.9 seconds
Standard Deviation 1.1
|
4.6 seconds
Standard Deviation 0.6
|
SECONDARY outcome
Timeframe: Before treatment (at baseline) and Post treatment (at the end of 2-week treatment)The following cognitive domains are assessed: executive function (Flanker inhibitory control and attention); cognitive flexibility (Dimensional Change Card Sort); working memory (List Sorting); short-term memory (Picture Sequence), processing speed (Pattern Comparison), Picture vocabulary and Oral Reading Recognition Tests. An overall composite score that combines these outcomes (Total Cognition Composite Score) is reported here. The higher value means better cognitive function. A score at or near 100 indicates ability that is average compared with others nationally. Scores around 115 suggest above-average cognitive ability, while scores around 130 suggest superior ability (in the top 2 percent nationally, based on Toolbox normative data). Conversely, a score around 85 suggests below-average cognitive ability, and a score in the range of 70 or below suggests significant impairment.
Outcome measures
| Measure |
RAVANS
n=8 Participants
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
n=7 Participants
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
|---|---|---|
|
NIH Toolbox Cognition Battery (NIHTB-CB)
Post Treatment
|
118.7 score on a scale
Standard Deviation 9.2
|
113.6 score on a scale
Standard Deviation 9.1
|
|
NIH Toolbox Cognition Battery (NIHTB-CB)
Before Treatment
|
109.8 score on a scale
Standard Deviation 7.6
|
107.2 score on a scale
Standard Deviation 4.7
|
SECONDARY outcome
Timeframe: Before treatment (baseline) and Post treatment (at the end of 2-week treatment)To determine if RAVANS treatment affects the level of inflammation
Outcome measures
| Measure |
RAVANS
n=8 Participants
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
n=7 Participants
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
|---|---|---|
|
Serum Level of Inflammatory Cytokines-IL6
Before Treatment
|
1897 fg/ml
Standard Deviation 1658
|
2648 fg/ml
Standard Deviation 1920
|
|
Serum Level of Inflammatory Cytokines-IL6
Post Treatment
|
2798 fg/ml
Standard Deviation 2391
|
2044 fg/ml
Standard Deviation 661
|
SECONDARY outcome
Timeframe: Before treatment (at baseline) and after treatment (at the end of 2-week treatment)To determine if RAVANS treatment affects the level of inflammation
Outcome measures
| Measure |
RAVANS
n=8 Participants
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
n=7 Participants
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
|---|---|---|
|
Serum Level of Inflammatory Cytokines-IL10
Before Treatment
|
668 fg/ml
Standard Deviation 293
|
742 fg/ml
Standard Deviation 308
|
|
Serum Level of Inflammatory Cytokines-IL10
Post Treatment
|
616 fg/ml
Standard Deviation 159
|
713 fg/ml
Standard Deviation 217
|
SECONDARY outcome
Timeframe: Before treatment (baseline) and Post treatment (at the end of 2-week treatment)To determine if RAVANS treatment affects the level of inflammation
Outcome measures
| Measure |
RAVANS
n=8 Participants
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
n=7 Participants
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
|---|---|---|
|
Serum Level of Inflammatory Cytokines-TNF Alfa
Before Treatment
|
473 fg/ml
Standard Deviation 95
|
492 fg/ml
Standard Deviation 137
|
|
Serum Level of Inflammatory Cytokines-TNF Alfa
Post Treatment
|
485 fg/ml
Standard Deviation 107
|
470 fg/ml
Standard Deviation 135
|
Adverse Events
RAVANS
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Sham Stimulation
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
RAVANS
n=8 participants at risk
active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks
respiratory-gated auricular vagal afferent nerve stimulation (RAVANS): non-painful electrical stimulation of the auricle
|
Sham Stimulation
n=7 participants at risk
Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks
Sham RAVANS: sham stimulation
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/8 • within the study period-2 weeks
|
14.3%
1/7 • Number of events 1 • within the study period-2 weeks
|
|
General disorders
Dizziness
|
12.5%
1/8 • Number of events 1 • within the study period-2 weeks
|
0.00%
0/7 • within the study period-2 weeks
|
|
General disorders
Headache
|
25.0%
2/8 • Number of events 2 • within the study period-2 weeks
|
0.00%
0/7 • within the study period-2 weeks
|
Additional Information
Qing Mei Wang, MD, PhD
Spaulding Rehabilitation Hospital
Phone: (617) 952-5299
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place