This open label clinical trial aims to assess the safety of abdominal vagus nerve stimulation (aVNS) for moderate to severe, adult-onset rheumatoid arthritis (RA) that has not responded to medication. The aVNS is an active medical device placed into the body to allow electrical stimulation of the abdominal vagus nerve. Participants will undergo stimulation treatment with the aVNS device from two to 24 weeks after the device is implanted by keyhole surgery. Safety, device performance and potential benefits will be assessed. Participants will be monitored for specific events for 5 years post surgery.
Male or female (18 - 75 years of age).
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).
Moderate-severe active RA defined by at least 4/28 tender and 4/28 swollen joints.
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).
Unable or unwilling to provide written informed consent.
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.
A medical condition that could interfere with study procedures, and/or confound evaluation of study endpoints, as determined by the Investigator.
Medical conditions that have resulted in severe autonomic neuropathy e.g. poorly controlled type 2 diabetes or metabolic disease.
Single group
abdominal vagus nerve stimulation (aVNS)
DeviceParticipants will receive aVNS, delivered by a commercially available stimulator placed under the skin, and a custom-designed electrode array attached to the abdominal vagus nerve. Stimulation will commence 2 weeks after laparoscopic surgical implantation of the device, and occur daily for 22-weeks stimulation in the initial phase of the study.
Safety of aVNS in individuals with drug refractory moderate-severe adult-onset RA.
Rate of recorded Serious Adverse Device Effects (SADEs) less than that for the Evoke® device (2%), a commercially available, FDA approved, CE marked implantable spinal cord stimulator.
Safety of aVNS in individuals with drug refractory moderate-severe adult-onset RA.
No significant increase in electrically Evoked Compound Action Potentials (ECAPs) threshold
Safety of aVNS in individuals with drug refractory moderate-severe adult-onset RA.
No significant decrease in amplitude of electrically Evoked Compound Action Potentials (ECAPs)
Performance of the aVNS System.
Rate of device deficiencies less than that for the Evoke® device
Exploratory Outcome: Non-futile benefits of aVNS in individuals with drug refractory moderate-severe adult-onset RA.
ACR 20, 50 or 70 response rates in DAS28-CRP from pre-surgery baseline levels.
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The Bionics Institute of Australia
Lead sponsor
St Vincent's Hospital Melbourne
Collaborator
Austin Health
Collaborator
