Vagus Nerve Stimulation for Rheumatoid Arthritis

(RESET-RA Trial)

Not currently recruiting at 46 trial locations

Overseen By Jamie Latos, DO

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 3

Sponsor: SetPoint Medical Corporation

Must be taking: Conventional DMARDs

Disqualifiers: Psychiatric illness, Cardiovascular disease, Neurological syndromes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new device, the SetPoint System, which could assist people with rheumatoid arthritis, particularly when other treatments have been ineffective. The device is implanted under the skin and sends signals to the vagus nerve, potentially reducing inflammation in the body. Participants will receive either the active device or a non-active one and will be monitored for effectiveness and safety. Individuals with swollen and tender joints despite using other arthritis drugs might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you continue taking at least one conventional synthetic DMARD (a type of medication for rheumatoid arthritis) at a stable dose through Week 12. The protocol does not specify if you need to stop other medications, so it's best to discuss this with the trial team.

What prior data suggests that the SetPoint System is safe for treating rheumatoid arthritis?

Research shows that the SetPoint System, a device used to stimulate the vagus nerve, has been tested in people with rheumatoid arthritis. Studies have found that the surgery to implant this device is safe, and patients have tolerated it well. Notably, vagus nerve stimulators have already been implanted in 100,000 people for various conditions, supporting its safety.

Moreover, the FDA has approved the SetPoint System for treating rheumatoid arthritis, indicating it has passed strict safety checks for this condition. Data from earlier trials confirmed its safety and effectiveness.

Overall, the SetPoint System has a strong safety record, supported by both research and regulatory approval. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for rheumatoid arthritis?

Researchers are excited about the SetPoint System for rheumatoid arthritis because it uses a cutting-edge approach called vagus nerve stimulation. Unlike traditional treatments, such as NSAIDs or biologics that primarily focus on reducing inflammation through chemical means, this therapy uses electrical stimulation to target inflammation directly by modulating the nervous system. This novel mechanism could offer a non-pharmacological option with potentially fewer side effects and open new avenues for managing rheumatoid arthritis.

What evidence suggests that the SetPoint System is effective for rheumatoid arthritis?

Research has shown that the SetPoint System, which employs vagus nerve stimulation (VNS), may help treat moderate to severe rheumatoid arthritis (RA). In earlier studies, this device improved symptoms in patients who did not respond well to other treatments. For instance, one study found that patients using the device achieved key treatment goals, such as the ACR20, which measures improvement in RA symptoms. This trial will compare active stimulation using the SetPoint System with a sham comparator. VNS sends signals to the brain that might help reduce inflammation, a major issue in RA. Overall, these findings suggest that the SetPoint System could be a useful option for managing RA symptoms. ^{1 2 3 6 7}

Who Is on the Research Team?

JOHN R TESSER

Principal Investigator

Arizona Arthritis and Rheumatology Research, P.C.

Mark Richardson, MD PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

Adults aged 22-75 with active, moderate to severe rheumatoid arthritis who haven't responded well or can't tolerate certain advanced RA medications. Participants must be on a stable dose of conventional synthetic DMARD for at least 12 weeks before the trial and continue it through Week 12. People with recurrent fainting episodes, significant psychiatric or substance abuse history, stroke/TIA, serious heart disease, neurological disorders like MS/Alzheimer's/Parkinson's, uncontrolled fibromyalgia, past carotid surgery/splenectomy/vagotomy or tobacco users are excluded.

Inclusion Criteria

I have rheumatoid arthritis and treatments like biologics or JAK inhibitors haven’t worked for me.

I have active rheumatoid arthritis with at least 4 tender and 4 swollen joints.

I have been on a stable dose of a DMARD for my condition for at least 12 weeks.

Exclusion Criteria

I have a condition that significantly weakens my immune system.

I frequently faint due to sudden drops in my heart rate and blood pressure.

I have had surgery on my carotid artery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implant Procedure

Surgical implantation of the miniaturized stimulator on the vagus nerve under general anesthesia

1 day

1 visit (in-person)

Treatment

Participants receive either active or non-active stimulation for 1 minute once per day

12 weeks

Weekly visits (in-person or virtual)

Crossover

Control subjects crossover to receive active stimulation

1 day

Open-label Follow-up

All subjects receive active stimulation to evaluate long-term safety

252 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SetPoint System

Trial Overview The RESET-RA study is testing the SetPoint System device that stimulates the vagus nerve to treat rheumatoid arthritis. The device is implanted via surgery under general anesthesia. Of the enrolled participants, half will receive actual stimulation while the other half will get non-active stimulation as a control group initially; after Week 12 all subjects will receive active stimulation for long-term safety assessment.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 3 Interventions

Active stimulation for 1 min once per day

Group II: Control Placebo Group 3 Interventions

Non-active stimulation for 1 min once per day

Who Is Running the Clinical Trial?

SetPoint Medical Corporation

Lead Sponsor

Trials

8

Recruited

400+

Published Research Related to This Trial

In a randomized, double-blind, sham-controlled trial involving 113 patients with rheumatoid arthritis, auricular vagus nerve stimulation (VNS) did not show a significant improvement in disease activity compared to sham treatment, with ACR20 response rates of 25.0% for active stimulation versus 26.9% for sham.

While there were some changes in secondary endpoints like the Health Assessment Questionnaire-Disability Index (HAQ-DI), the overall results suggest that VNS alone is not effective for managing rheumatoid arthritis, indicating the need for larger studies to explore its potential benefits in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind, Sham-Controlled, Clinical Trial of Auricular Vagus Nerve Stimulation for the Treatment of Active Rheumatoid Arthritis. Baker, MC., Kavanagh, S., Cohen, S., et al.[2023]

Vagus nerve stimulation (VNS) has shown promise in reducing inflammation and pain in various musculoskeletal diseases, including rheumatoid arthritis, with pilot studies indicating significant decreases in disease activity.

Both invasive and non-invasive VNS methods have been associated with benefits in conditions like Sjogren's syndrome and fibromyalgia, but further randomized controlled trials are needed to confirm these findings and determine optimal treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation in musculoskeletal diseases. Courties, A., Berenbaum, F., Sellam, J.[2021]

In a pilot study involving two patients with active rheumatoid arthritis who did not respond adequately to methotrexate, vagal nerve stimulation significantly improved clinical symptoms and inflammatory markers over a 42-day period.

After stopping the stimulation, both patients experienced a worsening of their symptoms, indicating that the effects of vagal stimulation may be temporary and highlighting the need for further research with more participants to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[VAGAL NERVE STIMULATION IN THE TREATMENT OF PATIENTS WITH RHEUMATOID ARTHRITIS – RESULTS THROUGH DAY 84 OBTAINED AT THE CROATIAN CENTER OF AN INTERNATIONAL PILOT STUDY]. Doko, I., Grazio, S., Grubišić, F., et al.[2018]

Abdominal vagus nerve stimulation (VNS) significantly reduced disease severity in a collagen-induced arthritis rat model, showing decreased inflammatory scores and ankle swelling compared to unstimulated rats.

Stimulated rats had undetectable levels of tumor necrosis factor-alpha (TNF-α) and significantly lower receptor activator of NFκB ligand (RANKL) levels, indicating that abdominal VNS may be an effective therapeutic approach for rheumatoid arthritis patients resistant to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abdominal vagus nerve stimulation alleviates collagen-induced arthritis in rats. Payne, SC., Romas, E., Hyakumura, T., et al.[2022]

Citations

1. setpointmedical.com setpointmedical.com/clinical-evidence/

Clinical Evidence Effective in improving disease activity. SetPoint System's effectiveness was studied in the RESET-RA study which met its primary effectiveness endpoint of ACR20 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04539964

NCT04539964 | Vagus Nerve Stimulation for Moderate to ... The RESET-RA study will assess the safety and efficacy of the SetPoint System (study device) for the treatment of adult patients with active, moderate to ...

3. setpointmedical.com setpointmedical.com/vagus-nerve-stimulation-proves-effective-in-refractory-rheumatoid-arthritis/

Vagus Nerve Stimulation Proves Effective in Refractory ... An implantable vagus nerve stimulation (VNS) device effectively treats moderate to severe rheumatoid arthritis (RA) in patients who had previously failed at ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38475923/

Clinical safety and feasibility of a novel ... The RESET-RA study was designed to determine the safety and efficacy of an active implantable device for treating RA.

5. rheumatologyadvisor.com rheumatologyadvisor.com/features/vagus-nerve-stimulation-for-rheumatoid-arthritis/

Vagus Nerve Stimulation for Rheumatoid Arthritis Results of a large, multicenter study by Ebina et al showed that nearly one-half of patients with RA discontinued DMARD therapy within 3 years.

6. setpointmedical.com setpointmedical.com/safety-and-efficacy-of-neurostimulation-with-a-miniaturised-vagus-nerve-stimulation-device-in-patients-with-multidrug-refractory-rheumatoid-arthritis/

Safety and efficacy of neurostimulation with a miniaturised ... We assessed the safety and efficacy of a novel miniaturised vagus nerve stimulation (VNS) device for the treatment of multidrug-refractory rheumatoid arthritis.

7. rheumatologyadvisor.com rheumatologyadvisor.com/news/fda-approves-neuroimmune-modulation-device-for-rheumatoid-arthritis/

FDA Approves Neuroimmune Modulation Device for ... The approval of the SetPoint System was supported by data from the randomized, double-blind, sham-controlled, phase 3 REST-RA trial ( ...