Transcutaneous Vagus Nerve Stimulation for the Treatment of Lupus

NCT02917265 | Terminated Phase 2 Results DMC FDA Device

• 1 other identifier: H15-141
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 3-month double blinded randomized controlled study of transcutaneous electrical vagus nerve stimulation (tVNS) compared to a sham stimulation for the treatment of patients with active systemic lupus erythematosus (SLE).

Conditions

Systemic Lupus Erythematosus

Keywords

vagus nerve stimulation; systemic lupus erythematosus

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants on Active vs Sham tVNS With Improvement in SLE Disease Activity by the BILAG-based Combined Lupus Assessment (BICLA)

  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

  12 weeks

Secondary Outcomes (2)

• Percentage of Participants on Active vs Sham tVNS With Improvement in SLE Disease Activity by the Systemic Lupus Erythematosus Responder Index (SRI-4)

  12 weeks

• Percentage of Participants on Active vs Sham tVNS With Improvement in Heart Rate Variability (HRV)

  12 weeks

Other Outcomes (2)

• Percentage of Participants on Active vs Sham tVNS That Experience an SLE Flare by SELENA SLEDAI Flare Index

  12 weeks

• Percentage of Participants on Active vs Sham tVNS With Improvement in Quality of Life Measured by the Lupus QoL

  12 weeks

Study Arms (2)

TENS for vagus stimulation

EXPERIMENTAL

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.

Device: TENS for vagus stimulation

TENS for sham stimulation

SHAM COMPARATOR

A TENS unit is applied to an area of the external ear that is devoid of vagus innervation.

Device: TENS for sham stimulation

Interventions

TENS for vagus stimulation DEVICE

TENS electrodes are applied on an area of the external ear innervated by the auricular branch of the vagus nerve.

TENS for vagus stimulation

TENS for sham stimulation DEVICE

TENS electrodes are applied on an area of the external ear devoid of vagus innervation.

TENS for sham stimulation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with SLE age 18-70 meeting the American College of Rheumatology Classification Criteria. Patients need to meet a minimum of 4 out of 11 criteria simultaneously or serially on two separate occasions.
• Positive antinuclear antibody or anti-dsDNA within one year of screening
• Non-serological SLEDAI ≥4 or ≥1 BILAG B or A and presence of inflammatory arthritis (defined by at least 3 swollen and 3 tender joints) at screening
• Patients may receive on one or more of the following immune suppressive therapies: hydroxychloroquine, quinacrine, methotrexate, azathioprine, mycophenolate mofetil, tacrolimus, sirolimus, belimumab, abatacept. Immune suppressive medications should have been administered at stable doses for ≥30 days prior to baseline. Patients may also be on prednisone up to 10mg daily or equivalent steroid treatment at the baseline visit.

You may not qualify if:

• Acute lupus nephritis defined as class II,III, IV or V nephritis diagnosed within 6 months or prot/creat \> 1.5 gm/gm due to active lupus or in process of receiving induction therapy for nephritis
• Active CNS lupus affecting mental status
• Any other organ threatening or life threatening manifestation of SLE as well as those, who, in the opinion of the investigator, have severe multi-organ or refractory lupus
• Rituximab treatment within 6 months prior to screening and/or without return of B cells to baseline levels
• Treatment with cyclophosphamide within a month prior to screening
• Treatment with any investigational drug within 3 months or 5 half-lives whichever is longer
• Recurrent vaso-vagal syncopal episodes
• Unilateral or bilateral vagotomy
• Presence of any evidence of vagus nerve pathology or injury
• Heart failure (NYHA class III or IV)
• Known atherosclerotic disease, including severe carotid artery disease, uncontrolled hypertension, uncontrolled diabetes, and history of myocardial infarction (MI), cardiomyopathy or stroke within the past year. Clinically stable patients with coronary artery disease, but no recent MI (within the past year) and no current symptoms of angina are not however excluded.
• Valvular and other structural heart disease that is evident by transthoracic echocardiogram and is associated with heart failure (NYHA class III or IV)
• Prolonged QT interval or abnormal baseline ECG - sick sinus syndrome, Mobitz type 2 second or third degree heart block, atrial fibrillation, atrial flutter, recent history of ventricular tachycardia or ventricular fibrillation or clinically significant premature ventricular contraction
• Individuals currently implanted with an electrical and/or neurostimulator device, such as cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, or cochlear implant
• Known respiratory disease that has decreased any pulmonary function test more than 25% below expected values or has resulted in hospitalization within the past year

Sponsors & Collaborators

• Aikaterini Thanou: lead
• Oklahoma Medical Research Foundation: collaborator
• University of Oklahoma: collaborator

Study Sites (1)

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Transcutaneous Electric Nerve Stimulation

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Physical Therapy Modalities; Rehabilitation; Analgesia; Anesthesia and Analgesia

Results Point of Contact

• Title: Aikaterini Thanou, MD
• Organization: Oklahoma Medical Research Foundation

aikaterini-thanou@omrf.org

405-271-7805

Study Officials

• Aikaterini Thanou, MD

  Oklahoma Medical Research Foundation

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Affiliate

Study Record Dates

• First Submitted: March 28, 2016
• First Posted: September 28, 2016
• Study Start: November 1, 2015
• Primary Completion: May 1, 2017
• Study Completion: November 1, 2018
• Last Updated: March 3, 2020
• Results First Posted: October 10, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)