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Vagus Nerve Stimulation for Moderate to Severe Rheumatoid Arthritis

NCT ID: NCT04539964

Last Updated: 2025-12-19

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

243 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-11

Study Completion Date

2027-10-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Rheumatoid Arthritis

Keywords

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Rheumatoid Arthritis Vagus nerve vagus nerve stimulating device drug refractory permanent implantable implant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
All subjects, investigators, joint evaluators and study staff will be blinded. Blinding of subjects, joint evaluators and investigators will be assessed at Weeks 4 and 12.

Study Groups

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Treatment

Active stimulation for 1 min once per day

Group Type EXPERIMENTAL

Implant Procedure

Intervention Type PROCEDURE

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 DMARD

Intervention Type DRUG

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 stimulation

Intervention Type DEVICE

Active stimulation for 1 min once per day

Control

Non-active stimulation for 1 min once per day

Group Type SHAM_COMPARATOR

Implant Procedure

Intervention Type PROCEDURE

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 DMARD

Intervention Type DRUG

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

Non-active stimulation

Intervention Type DEVICE

Non-active stimulation for 1 min once per day

Interventions

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Implant Procedure

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.

Intervention Type PROCEDURE

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

Intervention Type DRUG

Active stimulation

Active stimulation for 1 min once per day

Intervention Type DEVICE

Non-active stimulation

Non-active stimulation for 1 min once per day

Intervention Type DEVICE

Other Intervention Names

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Surgical placement of vagus nerve stimulator inside the neck Background therapy with conventional synthetic DMARD

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* 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
Minimum Eligible Age

22 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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SetPoint Medical Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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John Tesser, MD

Role: PRINCIPAL_INVESTIGATOR

Arizona Arthritis and Rheumatology Research, P.C.

Mark Richardson, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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Arizona Arthritis ans Rheumatology Research, PPLC

Mesa, Arizona, United States

Site Status

Arizona Arthritis Rheumatology & Research, PLLC

Phoenix, Arizona, United States

Site Status

Arizona Arthritis & Rheumatology Research, PLLC

Tucson, Arizona, United States

Site Status

Medvin Clinical Research

Covina, California, United States

Site Status

Inland Rheumatology Clinical Trials

Upland, California, United States

Site Status

Medvin Clinical Research

Whittier, California, United States

Site Status

The Arthritis & Rheumatology Clinic of Northern Colorado

Fort Collins, Colorado, United States

Site Status

Stamford Therapeutics Consortium

Stamford, Connecticut, United States

Site Status

Delaware Arthritis

Lewes, Delaware, United States

Site Status

Arthritis & Rheumatic Disease Specialties

Aventura, Florida, United States

Site Status

HARAC Research Corporation

Avon Park, Florida, United States

Site Status

RecioMed Clinical Research Network, Inc.

Boynton Beach, Florida, United States

Site Status

Bay Area Rheumatology

Clearwater, Florida, United States

Site Status

IRIS Research and Development

Plantation, Florida, United States

Site Status

Augusta University

Augusta, Georgia, United States

Site Status

Parris and Associates Rheumatology

Lawrenceville, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Willow Rheumatology and Wellness PLLC

Willowbrook, Illinois, United States

Site Status

Massachusetts General Hospital Division of Rheumatology, Allergy, and Immunology

Boston, Massachusetts, United States

Site Status

June DO, PC

Lansing, Michigan, United States

Site Status

Saint Paul Rheumatology, P.A.

Eagan, Minnesota, United States

Site Status

Kansas City Physician Partners

Kansas City, Missouri, United States

Site Status

West County Rheumatology

St Louis, Missouri, United States

Site Status

Physician Research Collaboration, LLC

Lincoln, Nebraska, United States

Site Status

Albuquerque Center for Rheumatology

Albuquerque, New Mexico, United States

Site Status

Long Island Regional Arthritis & Osteoporosis Care

Babylon, New York, United States

Site Status

DJL Clinical Research

Charlotte, North Carolina, United States

Site Status

Health Research of Oklahoma, PLLC

Oklahoma City, Oklahoma, United States

Site Status

Lehigh Valley Health Network

Allentown, Pennsylvania, United States

Site Status

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Arthritis & Rheumatology Research Institute, PLLC

Allen, Texas, United States

Site Status

Austin Regional Clinic

Austin, Texas, United States

Site Status

Tekton Research

Austin, Texas, United States

Site Status

Central Texas Rheumatology Associates

Austin, Texas, United States

Site Status

Precision Comprehensive Clinical Research Solutions

Colleyville, Texas, United States

Site Status

Biopharma Informatic

Houston, Texas, United States

Site Status

Southwest Rheumatology Research LLC

Mesquite, Texas, United States

Site Status

Clinical Trials of Texas, Inc

San Antonio, Texas, United States

Site Status

Annapolis Rheumatology

Fairfax, Virginia, United States

Site Status

Sound Clinical Research, LLC

Bothell, Washington, United States

Site Status

West Virginia University

Morgantown, West Virginia, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 38475923 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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SPM-020

Identifier Type: -

Identifier Source: org_study_id