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. 2024 Mar 13;10(1):8.
doi: 10.1186/s42234-023-00138-x.

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

Daniel Peterson  1 , Mark Van Poppel  2 , Warren Boling  3 , Perry Santos  4 , Jason Schwalb  5 , Howard Eisenberg  6 , Ashesh Mehta  7 , Heather Spader  8 , James Botros  9 , Frank D Vrionis  10 , Andrew Ko  11 , P David Adelson  12   13 , Bradley Lega  14 , Peter Konrad  13 , Guillermo Calle  15 , Fernando L Vale  16 , Richard Bucholz  17 , R Mark Richardson  18
Affiliations

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

Daniel Peterson et al. Bioelectron Med. .

Abstract

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes persistent synovitis, bone damage, and progressive joint destruction. Neuroimmune modulation through electrical stimulation of the vagus nerve activates the inflammatory reflex and has been shown to inhibit the production and release of inflammatory cytokines and decrease clinical signs and symptoms in RA. The RESET-RA study was designed to determine the safety and efficacy of an active implantable device for treating RA.

Methods: The RESET-RA study is a randomized, double-blind, sham-controlled, multi-center, two-stage pivotal trial that enrolled patients with moderate-to-severe RA who were incomplete responders or intolerant to at least one biologic or targeted synthetic disease-modifying anti-rheumatic drug. A neuroimmune modulation device (SetPoint Medical, Valencia, CA) was implanted on the left cervical vagus nerve within the carotid sheath in all patients. Following post-surgical clearance, patients were randomly assigned (1:1) to active stimulation or non-active (control) stimulation for 1 min once per day. A predefined blinded interim analysis was performed in patients enrolled in the study's initial stage (Stage 1) that included demographics, enrollment rates, device implantation rates, and safety of the surgical procedure, device, and stimulation over 12 weeks of treatment.

Results: Sixty patients were implanted during Stage 1 of the study. All device implant procedures were completed without intraoperative complications, infections, or surgical revisions. No unanticipated adverse events were reported during the perioperative period and at the end of 12 weeks of follow-up. No study discontinuations were due to adverse events, and no serious adverse events were related to the device or stimulation. Two serious adverse events were related to the implantation procedure: vocal cord paresis and prolonged hoarseness. These were reported in two patients and are known complications of surgical implantation procedures with vagus nerve stimulation devices. The adverse event of vocal cord paresis resolved after vocal cord augmentation injections with filler and speech therapy. The prolonged hoarseness had improved with speech therapy, but mild hoarseness persists.

Conclusions: The surgical procedures for implantation of the novel neuroimmune modulation device for the treatment of RA were safe, and the device and its use were well tolerated.

Trial registration: NCT04539964; August 31, 2020.

Keywords: Inflammatory reflex; Neuroimmune modulation; Rheumatoid arthritis; Vagus nerve stimulation.

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Conflict of interest statement

D.P., M.P., W.B., P.S., J.S., H.E., A.M., H.S., J.B., F.V., A.K., P.A., B.L., P.K., R.B., and M.R have nothing to disclose. G.C. is an employee of SetPoint Medical.

Figures

Fig. 1
Fig. 1
RESET-RA study design
Fig. 2
Fig. 2
Neuroimmune modulation system
Fig. 3
Fig. 3
CONSORT flow diagram
See this image and copyright information in PMC

Comment in

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