Abdominal vagus nerve stimulation for moderate to severe drug-refractory rheumatoid arthritis

The Reboot Study: A Single Group, Open Label Safety Study of Abdominal Vagus Nerve Stimulation for Moderate to Severe Drug Refractory Rheumatoid Arthritis

This trial will try a small implanted device that stimulates the abdominal vagus nerve to see if it is safe and possibly helpful for adults whose moderate to severe rheumatoid arthritis has not responded to medicines.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 5 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The Bionics Institute of Australia (Academic / other)
• Locations: 3 sites (Fitzroy, Victoria and 2 other locations)
• Trial ID: NCT07017686 on ClinicalTrials.gov

What this trial studies

This open-label first-in-indication pilot will enroll five adults with moderate to severe, drug-refractory rheumatoid arthritis to test an implanted abdominal vagus nerve stimulation (aVNS) device. The device is placed by keyhole surgery and participants will self‑administer stimulation for about three hours per day using an external controller during the initial 2–24 week phase. Primary outcomes at 24 weeks are safety and device performance, with exploratory checks for signs of clinical benefit at 12 and 24 weeks; participants will be seen at 2, 6, 12, and 24 weeks and may continue using the device thereafter. All participants will be followed for safety twice a year for up to five years after implantation.

Who should consider this trial

Good fit: Adults aged 18–75 with adult-onset, RF- or CCP/ACPA-positive rheumatoid arthritis who have moderate to severe active disease (at least 4/28 tender and 4/28 swollen joints) and who have not responded to or cannot tolerate at least two biologic or targeted synthetic DMARDs are the intended participants.

Not a fit: People with mild or well-controlled RA, seronegative RA, those unable or unwilling to undergo minor surgery, or those who are good responders to existing medications are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the approach could offer a new non-pharmacologic treatment option that reduces inflammation and symptoms for patients who no longer respond to current RA drugs.

How similar studies have performed: Small studies of cervical vagus nerve stimulation have shown promising signals for lowering inflammation in RA, but abdominal vagus nerve stimulation for RA is novel and has not been previously tested in this indication.

Eligibility criteria

Inclusion Criteria:

1. Male or female (18 - 75 years of age).
2. Adult-onset rheumatoid arthritis (RA) (onset age 18 years or above) as defined by the 2010 ACR/EULAR classification criteria, and Rheumatoid Factor (RF) or Cyclic Citrullinated Peptide (CCP) Antibody/Anti-Citrullinated Peptide Antibody (ACPA) must be positive (above lab ranges).
3. Moderate-severe active RA defined by at least 4/28 tender and 4/28 swollen joints.
4. Have active disease that has not responded to a 3-month trial of, or has intolerance limiting a full 3 month trial of, at least 2 biologic and/or new targeted synthetic DMARDs (e.g. JAK inhibitors).
5. Using a stable, continuous dose of at least 1 biological and/or synthetic DMARD for \>8 weeks prior to study screening and for the duration of the trial.
6. Women of childbearing age must not be pregnant or trying to become pregnant and must agree to use an effective method of contraception for the duration of their participation in the trial.
7. Medicare eligibility.
8. Provision of informed consent, in the form of a signed and dated informed consent form.

Exclusion Criteria:

1. Unable or unwilling to provide written informed consent.
2. Current diagnosis of major psychiatric disorder/s, or meets criteria as such on the Mini International Neuropsychiatric Interview (MINI), with the exception of stable, well controlled Major Depression or Anxiety Disorder.
3. A medical condition that could interfere with study procedures, and/or confound evaluation of study endpoints, as determined by the Investigator.
4. Medical conditions that have resulted in severe autonomic neuropathy e.g. poorly controlled type 2 diabetes or metabolic disease.
5. History of previous surgical interventions including vagotomy, splenectomy, bariatric surgery.
6. History of gastric hiatus hernia.
7. Previously implanted active medical devices (e.g., dorsal root ganglion or spinal cord stimulators, cardiac pacemakers, automatic implantable cardioverter-defibrillators, drug pumps), or likely need for implantation of such devices within 6 months after start of this study.
8. A condition that requires routine Magnetic Resonance Imaging (MRI) scans
9. Is, in the opinion of the Principal Investigator/s not a suitable candidate for the trial.

Where this trial is running

Fitzroy, Victoria and 2 other locations

• Bionics Institute — Fitzroy, Victoria, Australia (Recruiting)
• St Vincent's Hospital, Department of Rheumatology — Fitzroy, Victoria, Australia (Recruiting)
• Austin Health, Heidelberg Repatriation Hospital — Ivanhoe, Victoria, Australia (Recruiting)

Study contacts

• Principal investigator: A/Prof Shereen Oon — St Vincent's Hospital Melbourne
• Study coordinator: A/Prof Shereen Oon, MBBS, PhD

Conditions Arthritis, Rheumatoid; Neuromodulation; Inflammatory disease