Transcutaneous Vagus Nerve Stimulation in SLE

NCT06987565 | Not Yet Recruiting Phase 2

• 1 other identifier: 21-0331
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Systemic Lupus Erythematosus

Keywords

Systemic Lupus Erythematosus; Pain; Vagus nerve stimulation

Outcome Measures

Primary Outcomes (1)

• Change in Musculoskeletal Pain From Baseline.

  Patients rate their musculoskeletal pain by making a mark on a 10cm anchored Visual Analog Scale where 0=no musculoskeletal pain and 10 =worst possible musculoskeletal pain.

  28 days

Secondary Outcomes (75)

• Percentage of Subjects With Treatment Emergent Adverse Events.

  57 days

• Change in Musculoskeletal Pain From Baseline

  5 days

• Change in Musculoskeletal Pain From Baseline

  57 days

• Change in Musculoskeletal Pain From Day 29 to Day 57

  day 29 to day 57

• Fatigue

  5 days

Other Outcomes (31)

• Functional gut permeability

  Day 28

• Stool microbiome

  Day 28

• Gut permeability: serum I-FABP, zonulin and LPS, and by stool calprotectin and zonulin

  Day 28

Study Arms (2)

Vagus Nerve Stimulation

ACTIVE COMPARATOR

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

Device: Active vagus nerve stimulation

Sham Vagus Nerve Stimulation

PLACEBO COMPARATOR

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

Device: Sham vagus nerve stimulation

Interventions

Active vagus nerve stimulation 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.

Vagus Nerve Stimulation

Sham vagus nerve stimulation 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.

Sham Vagus Nerve Stimulation

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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,

Sponsors & Collaborators

• Northwell Health: lead
• Lupus Research Alliance: collaborator

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Pain

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Cynthia Aranow, MD

  Northwell Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sanita Kandasami

CONTACT

516 562-2401; skandasami@northwell.edu

Cynthia Aranow, MD

CONTACT

516 562-3845; caranow@northwell.edu

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: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2025
• First Posted: May 23, 2025
• Study Start: May 15, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: May 23, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: 6 months to 3 years after publication
• Access Criteria: Data will be available to researchers who provide a methodologically sound proposal and/or whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.