Trial Outcomes & Findings for Transcutaneous Vagus Nerve Stimulation for the Treatment of Lupus (NCT NCT02917265)

NCT ID: NCT02917265

Last Updated: 2020-03-03

Results Overview

Achieving a BICLA response requires to meet all of the following parameters: 1. All British Isles Lupus Assessment Group (BILAG) A scores improving to B/C/D and all BILAG level B scores improving to C/D 2. No single new BILAG A \& not \>1 new BILAG B scores, no worsening of the baseline Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) total score AND no worsening in the Physician Global Assessment (PGA) (\<10% worsening from baseline) 3. No initiation of non-protocol treatments or premature study discontinuation The range of values for the above instruments are listed below, with higher scores indicating more active disease: BILAG: 0 to 96 SLEDAI: 0 to 105 PGA: 0-3

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

12 weeks

Results posted on

2020-03-03

Participant Flow

Participants were recruited at the Rheumatology Research Clinic of the Oklahoma Medical Research Foundation between 9.2015 and 5.2017.

Screening and randomization occurred at the same visit. One individual failed screening due to severe depression.

Participant milestones

Participant milestones
Measure
TENS for Vagus Stimulation
A transcutaneous electrical nerve stimulation (TENS) unit is applied to tragus, the area of the external ear innervated by the auricular branch of the vagus nerve. TENS for vagus stimulation: TENS electrodes are applied the tragus of the external ear.
TENS for Sham Stimulation
A TENS unit is applied to the earlobe, an area of the external ear that is devoid of vagus innervation. TENS for sham stimulation: TENS electrodes are applied on the earlobe.
Overall Study
STARTED
5
2
Overall Study
COMPLETED
3
2
Overall Study
NOT COMPLETED
2
0

Reasons for withdrawal

Reasons for withdrawal
Measure
TENS for Vagus Stimulation
A transcutaneous electrical nerve stimulation (TENS) unit is applied to tragus, the area of the external ear innervated by the auricular branch of the vagus nerve. TENS for vagus stimulation: TENS electrodes are applied the tragus of the external ear.
TENS for Sham Stimulation
A TENS unit is applied to the earlobe, an area of the external ear that is devoid of vagus innervation. TENS for sham stimulation: TENS electrodes are applied on the earlobe.
Overall Study
Physician Decision
1
0
Overall Study
Withdrawal by Subject
1
0

Baseline Characteristics

Transcutaneous Vagus Nerve Stimulation for the Treatment of Lupus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
TENS for Vagus Stimulation
n=5 Participants
A transcutaneous electrical nerve stimulation (TENS) unit is applied to an area of the external ear that is innervated by the auricular branch of the vagus nerve. TENS for vagus stimulation: TENS electrodes are applied on an area of the external ear innervated by the auricular branch of the vagus nerve.
TENS for Sham Stimulation
n=2 Participants
A TENS unit is applied to an area of the external ear that is devoid of vagus innervation. TENS for sham stimulation: TENS electrodes are applied on an area of the external ear devoid of vagus innervation.
Total
n=7 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Age, Categorical
Between 18 and 65 years
4 Participants
n=99 Participants
2 Participants
n=107 Participants
6 Participants
n=206 Participants
Age, Categorical
>=65 years
1 Participants
n=99 Participants
0 Participants
n=107 Participants
1 Participants
n=206 Participants
Age, Continuous
50 years
n=99 Participants
51.5 years
n=107 Participants
50.4 years
n=206 Participants
Sex: Female, Male
Female
3 Participants
n=99 Participants
2 Participants
n=107 Participants
5 Participants
n=206 Participants
Sex: Female, Male
Male
2 Participants
n=99 Participants
0 Participants
n=107 Participants
2 Participants
n=206 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
5 Participants
n=99 Participants
2 Participants
n=107 Participants
7 Participants
n=206 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Race (NIH/OMB)
American Indian or Alaska Native
1 Participants
n=99 Participants
0 Participants
n=107 Participants
1 Participants
n=206 Participants
Race (NIH/OMB)
Asian
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Race (NIH/OMB)
Black or African American
2 Participants
n=99 Participants
1 Participants
n=107 Participants
3 Participants
n=206 Participants
Race (NIH/OMB)
White
2 Participants
n=99 Participants
1 Participants
n=107 Participants
3 Participants
n=206 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Region of Enrollment
United States
5 participants
n=99 Participants
2 participants
n=107 Participants
7 participants
n=206 Participants
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)
4.6 units on a scale
n=99 Participants
4 units on a scale
n=107 Participants
4.4 units on a scale
n=206 Participants

PRIMARY outcome

Timeframe: 12 weeks

Achieving a BICLA response requires to meet all of the following parameters: 1. All British Isles Lupus Assessment Group (BILAG) A scores improving to B/C/D and all BILAG level B scores improving to C/D 2. No single new BILAG A \& not \>1 new BILAG B scores, no worsening of the baseline Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) total score AND no worsening in the Physician Global Assessment (PGA) (\<10% worsening from baseline) 3. No initiation of non-protocol treatments or premature study discontinuation The range of values for the above instruments are listed below, with higher scores indicating more active disease: BILAG: 0 to 96 SLEDAI: 0 to 105 PGA: 0-3

Outcome measures

Outcome measures
Measure
TENS for Vagus Stimulation
n=5 Participants
A transcutaneous electrical nerve stimulation (TENS) unit is applied to tragus, the area of the external ear innervated by the auricular branch of the vagus nerve. TENS for vagus stimulation: TENS electrodes are applied the tragus of the external ear.
TENS for Sham Stimulation
n=2 Participants
A TENS unit is applied to the earlobe, an area of the external ear that is devoid of vagus innervation. TENS for sham stimulation: TENS electrodes are applied on the earlobe.
Percentage of Participants on Active vs Sham tVNS With Improvement in SLE Disease Activity by the BILAG-based Combined Lupus Assessment (BICLA)
BICLA responders
1 Participants
0 Participants
Percentage of Participants on Active vs Sham tVNS With Improvement in SLE Disease Activity by the BILAG-based Combined Lupus Assessment (BICLA)
BICLA non responders
4 Participants
2 Participants

SECONDARY outcome

Timeframe: 12 weeks

Population: all patients randomized to active treatment or placebo that had a total SLEDAI score of at least 4 at baseline.

SRI requires meeting all of the following parameters: 1. ≥4-point reduction from baseline in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score 2. No single new British Isles Lupus Assessment Group (BILAG) A score \& not \>1 new BILAG B scores AND no worsening in the Physician Global Assessment (PGA) (\<10% worsening from baseline) 3. No initiation of non-protocol treatments or premature study discontinuation The range of values for the above instruments are listed below, with higher scores indicating more active disease: BILAG: 0 to 96 SLEDAI: 0 to 108 PGA: 0-3

Outcome measures

Outcome measures
Measure
TENS for Vagus Stimulation
n=4 Participants
A transcutaneous electrical nerve stimulation (TENS) unit is applied to tragus, the area of the external ear innervated by the auricular branch of the vagus nerve. TENS for vagus stimulation: TENS electrodes are applied the tragus of the external ear.
TENS for Sham Stimulation
n=2 Participants
A TENS unit is applied to the earlobe, an area of the external ear that is devoid of vagus innervation. TENS for sham stimulation: TENS electrodes are applied on the earlobe.
Percentage of Participants on Active vs Sham tVNS With Improvement in SLE Disease Activity by the Systemic Lupus Erythematosus Responder Index (SRI-4)
SRI Responders
0 Participants
0 Participants
Percentage of Participants on Active vs Sham tVNS With Improvement in SLE Disease Activity by the Systemic Lupus Erythematosus Responder Index (SRI-4)
SRI Non-responders
4 Participants
2 Participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Analysis not done.

HRV is measured by time domain (RMSSD and pNN50) and frequency domain \[high frequency (HF), low to high frequency (LF/HF) ratio\] parameters.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Population: Analysis has not been done.

The SELENA SLEDAI flare index captures flares in the preceding 30 days by a combination of clinical descriptors and medications rules.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Population: Analysis not done.

The Lupus QoL is a patient reported outcome developed for measurement of quality of life of patients with SLE in clinical research

Outcome measures

Outcome data not reported

Adverse Events

TENS for Vagus Stimulation

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

TENS for 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

Other adverse events
Measure
TENS for Vagus Stimulation
n=5 participants at risk
A transcutaneous electrical nerve stimulation (TENS) unit is applied to tragus, the area of the external ear innervated by the auricular branch of the vagus nerve. TENS for vagus stimulation: TENS electrodes are applied the tragus of the external ear.
TENS for Sham Stimulation
n=2 participants at risk
A TENS unit is applied to the earlobe, an area of the external ear that is devoid of vagus innervation. TENS for sham stimulation: TENS electrodes are applied on the earlobe.
Renal and urinary disorders
Urinary tract infections
20.0%
1/5 • Number of events 1 • 12 weeks (baseline to Month 3)
0.00%
0/2 • 12 weeks (baseline to Month 3)
Nervous system disorders
headache
20.0%
1/5 • Number of events 1 • 12 weeks (baseline to Month 3)
50.0%
1/2 • Number of events 1 • 12 weeks (baseline to Month 3)
Gastrointestinal disorders
nausea
20.0%
1/5 • Number of events 1 • 12 weeks (baseline to Month 3)
0.00%
0/2 • 12 weeks (baseline to Month 3)
Nervous system disorders
paresthesias
0.00%
0/5 • 12 weeks (baseline to Month 3)
50.0%
1/2 • Number of events 1 • 12 weeks (baseline to Month 3)
Respiratory, thoracic and mediastinal disorders
cough
20.0%
1/5 • Number of events 1 • 12 weeks (baseline to Month 3)
0.00%
0/2 • 12 weeks (baseline to Month 3)
Nervous system disorders
carpal tunnel syndrome
20.0%
1/5 • Number of events 1 • 12 weeks (baseline to Month 3)
0.00%
0/2 • 12 weeks (baseline to Month 3)

Additional Information

Aikaterini Thanou, MD

Oklahoma Medical Research Foundation

Phone: 405-271-7805

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place