AzTrials
AzTrials

Rheumatoid ArthritisPhase 3RESET-RANCT04539964

Vagus Nerve Stimulation for Moderate to Severe Rheumatoid Arthritis

A Phase 3 study testing Implant Procedure, Conventional Synthetic DMARD and Active stimulation in people with Rheumatoid Arthritis, run by SetPoint Medical Corporation at 42 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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 severe rheumatoid arthritis who have had an inadequate response or intolerance to biologic or targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs). Read more about this study

Who is it for?
Ages 22 to 75 years
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
Implant Procedure, Conventional Synthetic DMARD and Active stimulation
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
243 participants
Where
42 sitesUnited States
Study dates
11 Jan 2021to Oct 2027
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 22 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 22-75 years of age at screening
  • Active moderate or severe RA, defined as at least 4/28 tender and 4/28 swollen joints
  • Demonstrated an inadequate response, loss of response, or intolerance to 1 or more approved for rheumatoid arthritis biologic or targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs), including Janus kinase inhibitors (JAKi)
  • Receiving treatment with at least 1 conventional synthetic DMARD for at least 12 weeks and on a continuous non-changing dose and route of administration for at least 4 weeks prior to Screening and able to continue the same stable dose through Week 12

Who cannot join

  • Untreated or poorly controlled psychiatric illness or history of substance abuse
  • Significant immunodeficiency due to underlying illness
  • History of stroke or transient ischemic attack, or diagnosis of cerebrovascular fibromuscular dysplasia
  • Clinically significant cardiovascular disease
  • Neurological syndromes, including multiple sclerosis, Alzheimer's disease, or Parkinson's disease
  • Uncontrolled fibromyalgia
Show all 11Show fewer
  • History of left or right carotid surgery
  • History of unilateral or bilateral vagotomy, partial or complete splenectomy
  • Recurrent vasovagal syncope episodes
  • Current, regular use of tobacco products
  • Hypersensitivity/allergy to MRI contrast agents and/or unable to perform MRI

Trial locations and contacts

42 sites in 1 country.

42 sites in 1 country

United States42 sites

  • Albuquerque Center for Rheumatology

    Albuquerque, New Mexico, 87102

  • Arthritis & Rheumatology Research Institute, PLLC

    Allen, Texas, 75013

  • Lehigh Valley Health Network

    Allentown, Pennsylvania, 18103

  • Augusta University

    Augusta, Georgia, 30912

  • Austin Regional Clinic

    Austin, Texas, 78717

  • Tekton Research

    Austin, Texas, 78745

  • Central Texas Rheumatology Associates

    Austin, Texas, 78746

  • Arthritis & Rheumatic Disease Specialties

    Aventura, Florida, 33180

  • HARAC Research Corporation

    Avon Park, Florida, 33825

  • Long Island Regional Arthritis & Osteoporosis Care

    Babylon, New York, 11702

  • Massachusetts General Hospital Division of Rheumatology, Allergy, and Immunology

    Boston, Massachusetts, 02114

  • Sound Clinical Research, LLC

    Bothell, Washington, 98021

  • RecioMed Clinical Research Network, Inc.

    Boynton Beach, Florida, 33472

  • Arthritis & Osteoporosis Consultants Of The Carolinas

    Charleston, North Carolina, 28202

  • DJL Clinical Research

    Charlotte, North Carolina, 28210

  • Northwestern University

    Chicago, Illinois, 60611

  • Bay Area Rheumatology

    Clearwater, Florida, 33765

  • Precision Comprehensive Clinical Research Solutions

    Colleyville, Texas, 76034

  • Medvin Clinical Research

    Covina, California, 91722

  • Saint Paul Rheumatology, P.A.

    Eagan, Minnesota, 55121

  • Annapolis Rheumatology

    Fairfax, Virginia, 22033

  • The Arthritis & Rheumatology Clinic of Northern Colorado

    Fort Collins, Colorado, 80528

  • Biopharma Informatic

    Houston, Texas, 77043

  • Kansas City Physician Partners

    Kansas City, Missouri, 64151

  • June DO, PC

    Lansing, Michigan, 48910

  • Parris and Associates Rheumatology

    Lawrenceville, Georgia, 30044

  • Delaware Arthritis

    Lewes, Delaware, 19958

  • Physician Research Collaboration, LLC

    Lincoln, Nebraska, 68516

  • Arizona Arthritis ans Rheumatology Research, PPLC

    Mesa, Arizona, 85210

  • Southwest Rheumatology Research LLC

    Mesquite, Texas, 75150

  • West Virginia University

    Morgantown, West Virginia, 26506

  • Health Research of Oklahoma, PLLC

    Oklahoma City, Oklahoma, 73103

  • University of Pennsylvania Medical Center

    Philadelphia, Pennsylvania, 19104

  • Arizona Arthritis Rheumatology & Research, PLLC

    Phoenix, Arizona, 85037

  • IRIS Research and Development

    Plantation, Florida, 33324

  • Clinical Trials of Texas, Inc

    San Antonio, Texas, 78229

  • West County Rheumatology

    St Louis, Missouri, 63122

  • Stamford Therapeutics Consortium

    Stamford, Connecticut, 06905

  • Arizona Arthritis & Rheumatology Research, PLLC

    Tucson, Arizona, 85704

  • Inland Rheumatology Clinical Trials

    Upland, California, 91786

  • Medvin Clinical Research

    Whittier, California, 90602

  • Willow Rheumatology and Wellness PLLC

    Willowbrook, Illinois, 60527

Other trials in United States

About this study

Official title: Vagus Nerve Stimulation Using the SetPoint System for Moderate to Severe Rheumatoid Arthritis: The RESET-RA Study

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 severe rheumatoid arthritis who have had an inadequate response or intolerance to biologic or targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs). The study device contains a miniaturized stimulator (implant) that is surgically placed under general anesthesia on the vagus nerve through a small incision on the left side of the neck (implant procedure). The study will enroll up to 250 subjects at up to 45 sites. All eligible subjects will undergo the implant procedure. Half of the subjects will receive active stimulation (treatment) and the other half will receive non-active stimulation (control). After completing primary endpoint assessments at Week 12, there will be a one-way crossover of control subjects to active stimulation and a 252-week open-label follow-up with all subjects (treatment and control) receiving active stimulation to evaluate long-term safety.

Read the detailed description

The RESET-RA study is an operationally seamless, 2-stage, randomized, double-blind, sham-controlled, multicenter pivotal study enrolling up to 250 subjects at up to 45 study centers across the U.S. The study will assess the safety and efficacy of the SetPoint System (study device) for the treatment of adult patients with active, moderate to severe rheumatoid arthritis (RA) who have had an inadequate response, loss of response or intolerance to biologic or targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs). The study device contains a miniaturized stimulator (implant) that is surgically implanted inside the left side of the neck on the vagus nerve (implant procedure). The implant delivers a small amount of electricity (stimulation) to the nerve. All eligible subjects will undergo the surgery under general anesthesia. Half of the subjects will receive active stimulation (the treatment group) and the other half will receive non-active stimulation (the control group). Stimulation will be delivered for 1 min once per day for 12 weeks. After completing primary endpoint assessments at Week 12, there will be a one-way crossover of control subjects to active stimulation and a 252-week open-label follow-up with all subjects (treatment and control) receiving active stimulation to evaluate long-term safety. Blinding will be maintained until the last enrolled and randomized subject in Stage 2 completes Week 12 assessments, and the study database is locked.

Being tested
Implant Procedure, Conventional Synthetic DMARD, Active stimulation, Non-active stimulation
Keywords
Rheumatoid Arthritis, Vagus nerve, vagus nerve stimulating device, drug refractory, permanent implantable, implant
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Implant ProcedureProcedure or surgery

    Also called Surgical placement of vagus nerve stimulator inside the neck

    The SetPoint System (study device) contains a miniaturized stimulator (implant) that is surgically implanted inside the left side of the neck on the vagus nerve (implant procedure). All eligible subjects will undergo the surgery under general anesthesia in outpatient settings.

  • Conventional Synthetic DMARDDrug

    Also called Background therapy with conventional synthetic DMARD

    All subjects will continue to take at least one type of conventional synthetic DMARD at the same stable dose as for 4 weeks prior to consent

  • Active stimulationDevice

    Active stimulation for 1 min once per day

  • Non-active stimulationDevice

    Non-active stimulation for 1 min once per day

Study groups in NCT04539964
Study groupRoleWhat they receive
TreatmentExperimentalActive stimulation for 1 min once per day
Receives: Procedure: Implant Procedure; Drug: Conventional Synthetic DMARD; Device: Active stimulation
ControlSham comparatorNon-active stimulation for 1 min once per day
Receives: Procedure: Implant Procedure; Drug: Conventional Synthetic DMARD; Device: Non-active stimulation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. the American College of Rheumatology (ACR) 20 Response

    Response is defined as achieving at least 20% improvement from baseline to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worst), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/L).

    Measured: Week 12

Secondary outcomes (4)

  1. DAS28-CRP Good or Moderate Response as Defined by European League Against Rheumatism (EULAR)

    The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) good or moderate response as defined by EULAR based on a composite score of 4 items: tender and swollen joint counts of 28 joints (scale 0=best to 28=worst), subject global assessment (0=best to 10=worst) and high-sensitivity C-reactive protein (hsCRP) concentration (mg/L). A total score ranges from 0 to 10 and is computed as follows:

    DAS28-CRP = 0.56 * sqrt(TJC28) + 0.28 * sqrt(SJC28) + 0.36 * ln(CRP+1) + 0.014 * SGA + 0.96

    A subject is considered having a moderate treatment response if:

    • DAS28-CRP score improvement from baseline to Week 12 is > 0.6 and ≤ 1.2, and the DAS28-CRP score at Week 12 is ≤ 5.1; or
    • DAS28-CRP score improvement from baseline to Week 12 is > 1.2, and the DAS28-CRP score at Week 12 is > 3.2.

    A subject is considered having a good treatment response if:

    • DAS28-CRP score improvement from baseline to Week 12 is > 1.2 and the DAS28-CRP score at Week 12 is ≤ 3.2

    Measured: Week 12

  2. DAS28-CRP Response (MCID -1.2) at Week 12

    The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) response is based on the minimal clinically important difference (MCID) of -1.2 from baseline.

    DAS28-CRP is based on a composite score of 4 items: tender and swollen joint counts of 28 joints (scale 0=best to 28=worst), subject global assessment (0=best to 10=worst) and high-sensitivity C-reactive protein (hsCRP) concentration (mg/L). A total score ranges from 0 to 10 and is computed as follows:

    DAS28-CRP = 0.56 * sqrt(TJC28) + 0.28 * sqrt(SJC28) + 0.36 * ln(CRP+1) + 0.014 * SGA + 0.96

    Measured: Week 12

  3. Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22)

    HAQ-DI response based on the MCID of -0.22 from baseline.

    The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas:

    • Dressing and grooming
    • Arising
    • Eating
    • Walking
    • Hygiene
    • Reach
    • Grip
    • Common daily activities

    Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability:

    • 0 to < 1 Mild difficulties to moderate disability
    • 1 to < 2 Moderate disability
    • 2 to 3 Severe to very severe disability

    Measured: Week 12

  4. ACR20 Response at Week 12 From Day 0

    Response is defined as achieving at least 20% improvement from Day 0 to Week 12 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worse), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/mL).

    Measured: Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Sep 2020
  2. Study start11 Jan 2021
  3. Primary completion16 May 2024
  4. Study completionOct 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
An operationally seamless, 2-stage, randomized, double-blind, sham-controlled, multicenter study. Subjects will be assigned randomly in a 1:1 ratio into either a treatment or control group. Subjects assigned to the treatment group will receive active stimulation for 1 min once per day, and those assigned to the control group will receive non-active stimulation for 1 min once per day.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
243 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04539964
Sponsor's protocol ID
SPM-020
Acronym
RESET-RA
Status last verified
Jan 2026
First submitted
31 Aug 2020
Last updated
14 Apr 2026
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No: No sharing data is planned.

Publications

  • Tesser JRP, Crowley AR, Box EJ, June JP, Wickersham PB, Valenzuela GJ, Gaylis NB, Lam GKW, Pacheco LA, Ridley DJ, Pinto-Patarroyo GP, Novack SN, Churchill MA, Kohler M, Lee EC, Pando JA, Parris GR, Peterson JR, Shah T, Singhal AK, Vuong V, Levine YA, Evangelista ML, Derosier AA, Curtis JR, Richardson RM, Chernoff D. Vagus nerve-mediated neuroimmune modulation for rheumatoid arthritis: a pivotal randomized controlled trial. Nat Med. 2026 Jan;32(1):369-378. doi: 10.1038/s41591-025-04114-7. Epub 2025 Dec 22.

    PubMed 41429981

  • Peterson D, Van Poppel M, Boling W, Santos P, Schwalb J, Eisenberg H, Mehta A, Spader H, Botros J, Vrionis FD, Ko A, Adelson PD, Lega B, Konrad P, Calle G, Vale FL, Bucholz R, Richardson RM. Clinical safety and feasibility of a novel implantable neuroimmune modulation device for the treatment of rheumatoid arthritis: initial results from the randomized, double-blind, sham-controlled RESET-RA study. Bioelectron Med. 2024 Mar 13;10(1):8. doi: 10.1186/s42234-023-00138-x.

    PubMed 38475923

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Implant Procedure, Conventional Synthetic DMARD and Active stimulation in people with Rheumatoid Arthritis, run by SetPoint Medical Corporation at 42 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 14 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

the American College of Rheumatology (ACR) 20 Response (time frame: Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04539964, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in