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Transcutaneous Vagus Nerve Stimulation for the Treatment of Lupus (TRUST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02917265
Recruitment Status : Terminated (poor recruitment)
First Posted : September 28, 2016
Results First Posted : October 10, 2019
Last Update Posted : March 3, 2020
Sponsor:
Collaborators:
Oklahoma Medical Research Foundation
University of Oklahoma
Information provided by (Responsible Party):
Aikaterini Thanou, Oklahoma Medical Research Foundation

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Systemic Lupus Erythematosus
Interventions Device: TENS for vagus stimulation
Device: TENS for sham stimulation
Enrollment 7
Recruitment Details Participants were recruited at the Rheumatology Research Clinic of the Oklahoma Medical Research Foundation between 9.2015 and 5.2017.
Pre-assignment Details Screening and randomization occurred at the same visit. One individual failed screening due to severe depression.
Arm/Group Title TENS for Vagus Stimulation TENS for Sham Stimulation
Hide Arm/Group Description

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.

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.

Period Title: Overall Study
Started [1] 5 2
Completed [2] 3 2
Not Completed 2 0
Reason Not Completed
Physician Decision             1             0
Withdrawal by Subject             1             0
[1]
11.2015
[2]
5.2017
Arm/Group Title TENS for Vagus Stimulation TENS for Sham Stimulation Total
Hide Arm/Group Description

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.

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 of all reporting groups
Overall Number of Baseline Participants 5 2 7
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 2 participants 7 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
4
  80.0%
2
 100.0%
6
  85.7%
>=65 years
1
  20.0%
0
   0.0%
1
  14.3%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 5 participants 2 participants 7 participants
50
(25 to 69)
51.5
(43 to 60)
50.4
(25 to 69)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 2 participants 7 participants
Female
3
  60.0%
2
 100.0%
5
  71.4%
Male
2
  40.0%
0
   0.0%
2
  28.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 2 participants 7 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
5
 100.0%
2
 100.0%
7
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 2 participants 7 participants
American Indian or Alaska Native
1
  20.0%
0
   0.0%
1
  14.3%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
  40.0%
1
  50.0%
3
  42.9%
White
2
  40.0%
1
  50.0%
3
  42.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 5 participants 2 participants 7 participants
5 2 7
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)   [1] 
Mean (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 5 participants 2 participants 7 participants
4.6
(4 to 6)
4
(2 to 6)
4.4
(2 to 6)
[1]
Measure Description:

The SLEDAI is the sum score of 24 variables to assess global lupus disease activity in the preceding 30 days. Scores can range from zero (no disease activity) to 105 (very active systemic lupus).

Disease activity categories: no activity: SLEDAI = 0, mild disease activity: SLEDAI = 1–5, moderate disease activity: SLEDAI = 6–10, high disease activity: SLEDAI = 11–19, very high disease activity: SLEDAI >20

1.Primary Outcome
Title Percentage of Participants on Active vs Sham tVNS With Improvement in SLE Disease Activity by the BILAG-based Combined Lupus Assessment (BICLA)
Hide Description

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

Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title TENS for Vagus Stimulation TENS for Sham Stimulation
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 5 2
Measure Type: Count of Participants
Unit of Measure: Participants
BICLA responders
1
  20.0%
0
   0.0%
BICLA non responders
4
  80.0%
2
 100.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TENS for Vagus Stimulation, TENS for Sham Stimulation
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants on Active vs Sham tVNS With Improvement in SLE Disease Activity by the Systemic Lupus Erythematosus Responder Index (SRI-4)
Hide Description

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

Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
all patients randomized to active treatment or placebo that had a total SLEDAI score of at least 4 at baseline.
Arm/Group Title TENS for Vagus Stimulation TENS for Sham Stimulation
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 4 2
Measure Type: Count of Participants
Unit of Measure: Participants
SRI Responders
0
   0.0%
0
   0.0%
SRI Non-responders
4
 100.0%
2
 100.0%
3.Secondary Outcome
Title Percentage of Participants on Active vs Sham tVNS With Improvement in Heart Rate Variability (HRV)
Hide Description HRV is measured by time domain (RMSSD and pNN50) and frequency domain [high frequency (HF), low to high frequency (LF/HF) ratio] parameters.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis not done.
Arm/Group Title TENS for Vagus Stimulation TENS for Sham Stimulation
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Other Pre-specified Outcome
Title Percentage of Participants on Active vs Sham tVNS That Experience an SLE Flare by SELENA SLEDAI Flare Index
Hide Description The SELENA SLEDAI flare index captures flares in the preceding 30 days by a combination of clinical descriptors and medications rules.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis has not been done.
Arm/Group Title TENS for Vagus Stimulation TENS for Sham Stimulation
Hide Arm/Group Description:

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.

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 Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Other Pre-specified Outcome
Title Percentage of Participants on Active vs Sham tVNS With Improvement in Quality of Life Measured by the Lupus QoL
Hide Description The Lupus QoL is a patient reported outcome developed for measurement of quality of life of patients with SLE in clinical research
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis not done.
Arm/Group Title TENS for Vagus Stimulation TENS for Sham Stimulation
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame 12 weeks (baseline to Month 3)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title TENS for Vagus Stimulation TENS for Sham Stimulation
Hide Arm/Group Description

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.

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.

All-Cause Mortality
TENS for Vagus Stimulation TENS for Sham Stimulation
Affected / at Risk (%) Affected / at Risk (%)
Total   0/5 (0.00%)      0/2 (0.00%)    
Hide Serious Adverse Events
TENS for Vagus Stimulation TENS for Sham Stimulation
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/5 (0.00%)      0/2 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
TENS for Vagus Stimulation TENS for Sham Stimulation
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/5 (80.00%)      1/2 (50.00%)    
Gastrointestinal disorders     
nausea *  1/5 (20.00%)  1 0/2 (0.00%)  0
Nervous system disorders     
headache *  1/5 (20.00%)  1 1/2 (50.00%)  1
paresthesias *  0/5 (0.00%)  0 1/2 (50.00%)  1
carpal tunnel syndrome *  1/5 (20.00%)  1 0/2 (0.00%)  0
Renal and urinary disorders     
Urinary tract infections *  1/5 (20.00%)  1 0/2 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
cough *  1/5 (20.00%)  1 0/2 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Aikaterini Thanou, MD
Organization: Oklahoma Medical Research Foundation
Phone: 405-271-7805
EMail: aikaterini-thanou@omrf.org
Layout table for additonal information
Responsible Party: Aikaterini Thanou, Oklahoma Medical Research Foundation
ClinicalTrials.gov Identifier: NCT02917265    
Other Study ID Numbers: H15-141
First Submitted: March 28, 2016
First Posted: September 28, 2016
Results First Submitted: February 16, 2019
Results First Posted: October 10, 2019
Last Update Posted: March 3, 2020