The Reboot Study: A Safety Study of Abdominal Vagus Nerve Stimulation for Moderate to Severe Drug Refractory Rheumatoid Arthritis (Reboot)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Device: abdominal vagus nerve stimulation (aVNS)

Detailed Description

This open label first-in-indication study will assess safety of an abdominal vagus nerve stimulation (aVNS) device in 5 adult participants with moderate to severe drug refractory rheumatoid arthritis (RA). The trial primary objectives at 24 weeks are to assess: 1) safety of aVNS and; 2) device performance. An exploratory objective is to assess non-futile benefits of aVNS at 12 and 24 weeks. During the initial phase of the study (2-24 weeks), stimulation will be delivered for 3 hours per day, with the participant switching the device on and off via a controller. Reports of safety, device checks and clinical assessment of RA symptoms will occur during at 2-, 6-, 12- and 24-weeks post-surgery. Participants that complete the initial phase of the study (24 week assessment) will have the option to continue using the device. Participants that do not want to continue treatment, or withdraw, will have their device deactivated. The device will remain implanted unless there is a clinical reason to remove it or if the participant requests removal. During the follow up phase of the safety trial (24-265 weeks), participants will be monitored twice a year for up to 5 years. The total duration of involvement of participants will be approximately 5 years.

• Study Type: Interventional
• Enrollment (Estimated): 5
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: A/Prof Shereen Oon, MBBS, PhD; Phone Number: +61392311203; Email: rheumclintrials@svha.org.au
• Study Contact Backup: Name: Angela Chia, RN; Phone Number: +61392311203; Email: rheumclintrials@svha.org.au

Study Locations

• Australia
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Recruiting
      • Bionics Institute
    • Fitzroy, Victoria, Australia, 3065
      • Recruiting
      • St Vincent's Hospital, Department of Rheumatology
    • Ivanhoe, Victoria, Australia, 3079
      • Recruiting
      • Austin Health, Heidelberg Repatriation Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: abdominal vagus nerve stimulation (aVNS); Participants will receive aVNS, delivered by the implanted aVNS device.

Device: abdominal vagus nerve stimulation (aVNS); Participants 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.; Other Names: IBDStim; Vagus Nerve Stimulator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 weeks
Safety of aVNS in individuals with drug refractory moderate-severe adult-onset RA.	No significant increase in electrically Evoked Compound Action Potentials (ECAPs) threshold	24 weeks
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)	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance of the aVNS System.	Rate of device deficiencies less than that for the Evoke® device	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to week 6, 12 or 24 assessment.

Collaborators and Investigators

• Sponsor: The Bionics Institute of Australia
• Collaborators: St Vincent's Hospital Melbourne; Austin Health
• Investigators: Principal Investigator: A/Prof Shereen Oon, St Vincent's Hospital Melbourne

Publications and helpful links

General Publications

• Payne, S. C., Burns, O., Stebbing, M., Thomas, R., Silva, A. de, Sedo, A., … Shepherd, R. K. (2018). Vagus Nerve Stimulation to Treat Inflammatory Bowel Disease: A Chronic, Preclinical Safety Study in Sheep. Bioelectronics in Medicine, 1(4), 235-250. https://doi.org/10.2217/bem-2018-0011
• Payne SC, Furness JB, Stebbing MJ. Bioelectric neuromodulation for gastrointestinal disorders: effectiveness and mechanisms. Nat Rev Gastroenterol Hepatol. 2019 Feb;16(2):89-105. doi: 10.1038/s41575-018-0078-6.
• Payne SC, Furness JB, Burns O, Sedo A, Hyakumura T, Shepherd RK, Fallon JB. Anti-inflammatory Effects of Abdominal Vagus Nerve Stimulation on Experimental Intestinal Inflammation. Front Neurosci. 2019 May 8;13:418. doi: 10.3389/fnins.2019.00418. eCollection 2019.
• Payne SC, Romas E, Hyakumura T, Muntz F, Fallon JB. Abdominal vagus nerve stimulation alleviates collagen-induced arthritis in rats. Front Neurosci. 2022 Nov 21;16:1012133. doi: 10.3389/fnins.2022.1012133. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: June 4, 2025
• First Submitted That Met QC Criteria: June 4, 2025
• First Posted (Actual): June 12, 2025

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Neuromodulation; Inflammatory disease
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Arthritis, Rheumatoid
• Other Study ID Numbers: 107360; 122/24 (St Vincent's Hospital Melbourne Human Research Ethics Committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No