Transcutaneous Vagus Nerve Stimulation in SLE

NCT ID: NCT06987565

Last Updated: 2025-05-23

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-15
• Study Completion Date: 2027-05-31

Brief Summary

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease. Joint and muscle pain and fatigue are extremely common among patients and contribute to a reduced quality of life. Available therapies may be associated with significant side effects and many patients do not achieve an adequate response to these treatments. Therefore, there is an unmet need to develop new strategies to reduce pain and fatigue. Filling this need would significantly improve patients' quality of life. This trial will evaluate the effects of a novel approach, stimulating the vagus nerve, a nerve originating in the brain as a potential therapeutic intervention for treatment of musculoskeletal pain and fatigue. Vagus nerve stimulation has multiple beneficial effects and is one of the body's own ways to modulate the immune system. One can stimulate the vagus nerve via the skin at the neck or at specific locations in the ear, (transcutaneous vagus nerve stimulation: tcVNS). We recently completed a short, small scale randomized, placebo controlled trial of tcVNS in patients with SLE and observed dramatic benefits on musculoskeletal pain and fatigue. The treatment was safe without side effects. We are therefore proposing a longer trial to validate our initial findings and to look at durability. In this study, 18 patients with musculoskeletal pain will be followed for 2 months and will receive tcVNS or placebo (sham stimulation) for 5 minutes/day for 28 days. Patients will have a 1 out of 3 chance of receiving sham stimulation and neither the patient nor the evaluating investigator will know the actual treatment. The stimulations are self-administered, are non-painful and have not been associated with serious risks. After 28 days of stimulation, treatment will be discontinued and patients will be monitored for an additional 28 days to evaluate durability. Pain, fatigue and disease activity will be evaluated as well as possible side effects will be monitored throughout the trial. This study will also explore biologic mechanisms that may be responsible for the potential clinical effects. This will include possible effects of stimulation on gut permeability and the stool microbiome, areas that may play a significant role contributing to SLE disease and its manifestations. The development of an effective treatment without significant side effects would be extremely valuable and a significant advance for patients with SLE. If efficacious, tcVNS offers a non-toxic, non-immunosuppressive strategy to control two of the most common symptoms of this disease.

Detailed Description

Musculoskeletal (MS) pain and fatigue are common symptoms of patients with Systemic Lupus Erythematosus (SLE) affecting up to 95% and contributing to a reduced quality of life. Safe and efficacious treatment remains an unmet need for these disease manifestations. Stimulation of the vagus nerve results in beneficial effects in patients. We recently completed a short , small scale, randomized, sham-controlled, double blind clinical trial of transcutaneous vagus nerve stimulation (taVNS) in patients with SLE. The clinical benefit on MS pain and fatigue was dramatic. We now propose a randomized sham controlled clinical trial assessing the efficacy and durability of a longer exposure to taVNS (28 days in comparison to the 4 day exposure in the previous trial) in 18 patients randomized 2: 1 with musculoskeletal pain. After 28 days of stimulation, the treatment will be discontinued and patients will be monitored for an additional 28 days to evaluate the treatment's durability. Pain, fatigue, disease activity (global and musculoskeletal) and safety will be evaluated and safety will be monitored throughout the trial. In this clinical trial we will also explore potential biologic mechanisms and pathways by which taVNS exerts ifs effects in SLE, including potential effects on gut permeability and the microbiome.

Conditions

Systemic Lupus Erythematosus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Vagus Nerve Stimulation

Patients will receive transcutaneous stimulation of the left vagus nerve for 5 minutes daily for 28 consecutive days.

Group Type: ACTIVE_COMPARATOR

Active vagus nerve stimulation

Intervention Type: DEVICE

Patients will receive transcutaneous stimulation of the vagus nerve for 5 minutes daily for 28 consecutive days. The device is a handheld electrical pulse generator and a pair of electrodes will be placed on the skin for stimulation. The electrical pulse generator is turned on and the amplitude of stimulation increased to the greatest amount tolerated. Patients will be followed through day 57 to assess durability of the intervention.

Sham Vagus Nerve Stimulation

Patients will receive sham transcutaneous stimulation of the of the left vagus nerve for 5 minutes daily for 28 consecutive days.

Group Type: PLACEBO_COMPARATOR

Sham vagus nerve stimulation

Intervention Type: DEVICE

Patients will receive transcutaneous stimulation of the vagus nerve for 5 minutes daily for 28 consecutive days. The device is a handheld electrical pulse generator and a pair of electrodes will be placed on the skin for stimulation. The electrical pulse generator is turned on and the amplitude of stimulation increased to the greatest amount tolerated, however, the vagus nerve will not be stimulated. Patients will be followed through day 57 to assess durability of the intervention.

Interventions

Active vagus nerve stimulation

Patients will receive transcutaneous stimulation of the vagus nerve for 5 minutes daily for 28 consecutive days. The device is a handheld electrical pulse generator and a pair of electrodes will be placed on the skin for stimulation. The electrical pulse generator is turned on and the amplitude of stimulation increased to the greatest amount tolerated. Patients will be followed through day 57 to assess durability of the intervention.

Intervention Type: DEVICE

Sham vagus nerve stimulation

Patients will receive transcutaneous stimulation of the vagus nerve for 5 minutes daily for 28 consecutive days. The device is a handheld electrical pulse generator and a pair of electrodes will be placed on the skin for stimulation. The electrical pulse generator is turned on and the amplitude of stimulation increased to the greatest amount tolerated, however, the vagus nerve will not be stimulated. Patients will be followed through day 57 to assess durability of the intervention.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• SLE (defined by the ACR or SLICC criteria),
• Musculoskeletal pain ≥ 4 on a non-anchored VAS 10 cm scale,
• BILAG C or greater on the Musculoskeletal Domain of the BILAG 2004,
• If on corticosteroids, the dose must be stable and ≤ 10 mg/day (prednisone or equivalent) for at least 14 days before baseline,
• If on background immunosuppressive treatment the dose must be stable for at least 28 days before baseline,
• If on NSAIDS, the dose must be stable for at least 7 days before baseline and the subject must be willing not to change the dose during the trial (except for toxicity),
• Able and willing to give written informed consent and comply with the requirements of the study protocol.

Exclusion Criteria

• Initiation of immunosuppressive or antimalarial treatment within 3 months of baseline,
• Treatment with cyclophosphamide within 2 months of baseline,
• Initiation of anifrolumab within 3 months of baseline
• Initiation of belimumab within 6 months of baseline,
• Expectation to increase steroids and/or immunosuppressive treatment,
• Anti-phospholipid syndrome,
• Fibromyalgia,
• Treatment with an anti-cholinergic medication, including over the counter medications,
• Any implantable electronic devices including pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators,
• Current tobacco or nicotine user (to limit potential confounding effects of exposure to nicotine),
• Joint replacement within 60 days prior to study enrollment or planned within the course of the study,
• Any planned surgical procedure requiring general anesthesia within the course of the study,
• Intra-articular cortisone injections within 28 days of the start of study,
• Chronic inflammatory disorders apart from SLE affecting the joints,
• Investigational drug and/or treatment during the 28 days or seven half-lives of the investigational drug prior to the start of study drug dosing (Day 0), whichever is the greater length of time,
• Active infection including hepatitis B or hepatitis C at baseline,
• Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to a study intervention,
• Pregnancy or lactation (Pregnancy status will be determined via serum blood test & lactation will be determined via self-report),
• Comorbid disease that has previously required administration of corticosteroid use,
• Known allergy to mannitol or lactulose,
• Chronic treatment with narcotic medication,
• Prior receipt of transauricular vagus nerve stimulation in a clinical trial,
• Inability to comply with study and follow-up procedures.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lupus Research Alliance

OTHER

Sponsor Role: collaborator

Northwell Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cynthia Aranow, MD

Role: PRINCIPAL_INVESTIGATOR

Northwell Health

Central Contacts

Sanita Kandasami

Role: CONTACT

skandasami@northwell.edu

516 562-2401

Cynthia Aranow, MD

Role: CONTACT

caranow@northwell.edu

516 562-3845

Other Identifiers

21-0331

Identifier Type: -

Identifier Source: org_study_id