The SetPoint System as a Pro-Remyelination Therapy for Relapsing-Remitting Multiple Sclerosis: A Pilot Study

The MS pilot study will assess the safety and investigate the remyelinating effects of the SetPoint System (study device) in adult patients with patients diagnosed with relapsing-remitting multiple sclerosis (RRMS). The SetPoint System is intended for adjunctive use with standard of care therapy for RRMS. 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 60 participants at up to 10 sites. All eligible participants will undergo the implant procedure. Two-thirds of the participants will receive active stimulation (treatment) and the one-third will receive non-active stimulation (control). Following treatment evaluations at Week 48, there will be a one-way crossover of control subjects to active stimulation and a 48-week open-label follow-up with all subjects (treatment and control) receiving active stimulation to evaluate long-term safety.

Study Overview

• Status: Recruiting
• Conditions: Relapsing Remitting Multiple Sclerosis
• Intervention / Treatment: Procedure: Procedure/Surgery: Implant Procedure; Drug: Disease-Modifying Therapies (DMTs); Device: Device: Active stimulation; Device: Device: Non-active stimulation

Detailed Description

The MS pilot study is a 2:1 randomized, double-blind, sham-controlled, multi-center pivotal study enrolling up to 60 subjects at up to 10 study centers across the U.S. The study will assess the safety and investigate the remyelinating effects of the SetPoint System (study device) in adult patients with patients diagnosed with relapsing-remitting multiple sclerosis (RRMS). The SetPoint System is intended for adjunctive use with standard of care therapy for RRMS. 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. Two-thirds of the subjects will receive active stimulation (the treatment group) and the other one-third will receive non-active stimulation (the control group). Stimulation will be delivered for 1 min once per day for 48 weeks. Following treatment evaluations at Week 48, there will be a one-way crossover of control subjects to active stimulation and a 48-week open-label follow-up with all subjects (treatment and control) receiving active stimulation to evaluate long-term safety. Blinding will be maintained for each individual participant until that participant has completed their Week 48 assessments.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Paula Timm; Email: ptimm@setpointmedical.com
• Study Contact Backup: Name: Amy Derosier; Email: aderosier@setpointmedical.com

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Recruiting
      • Shepherd Center
      • Contact: Michelle Tidwell; Phone Number: 404-367-1317; Email: Michelle.Tidwell@shepherd.org
      • Principal Investigator: Jacqueline Rosenthal, MD
      • Contact: Cathy Furbish; Phone Number: 404-350-7591; Email: Cathy.Furbish@shepherd.org
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins School of Medicine
      • Principal Investigator: Bardia Nourbakhsh, MD
      • Contact: Adam Didouchevski; Phone Number: 443-818-1451; Email: adidouc1@jh.edu
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Recruiting
      • Minnesota Center for Multiple Sclerosis
      • Principal Investigator: Jonathan Calkwood, MD
      • Contact: Halie Kaufman; Phone Number: 763-243-8180; Email: HKaufman@vivoinfusion.com
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas Health Science Center at Houston
      • Contact: Tanya Khan; Phone Number: 713-704-0823; Email: Tanya.S.Khan@uth.tmc.edu
      • Principal Investigator: John Lincoln, MD
  • Washington
    • Seattle, Washington, United States, 98133
      • Recruiting
      • UW Medicine Multiple Sclerosis Center-Northwest
      • Contact: Elisa McGee; Phone Number: 206-598-9260; Email: emcgee@uw.edu
      • Principal Investigator: Yujie Wang, MD
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Recruiting
      • West Virginia University
      • Principal Investigator: Melanie Ward, MD
      • Contact: Lauren Chase; Phone Number: 179418 304-598-4000; Email: lauren.chase@wvumedicine.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 22-50 years at informed consent.
• Diagnosis of RRMS by revised 2017 McDonald criteria.
• Latency delay >118 milliseconds on baseline full-field transient pattern reversal visual evoked potential (VEP) in at least one eye. Both eyes can be included if they meet all inclusion criteria.
• Peri-papillary retinal nerve fiber layer (pRNFL) > 70 microns on Optical Coherence Topography (OCT) in the VEP-qualifying eye (sufficient axons).
• Best corrected high-contrast (HCVA) better than 20/200 Snellen equivalent or letter score of 35
• Best corrected low-contrast letter acuity (LCLA) by Sloan chart (2.5% black on white) of no better than 40 letters in the VEP-qualifying eye (Snellen equivalent of 20/40). (Best corrected LCLA must be worse than best corrected HCVA.)
• Absence of clinical relapse for at least 12 months prior to informed consent
• No new lesions or increase in existing lesion volume on most recent clinic brain MRI (must be within 1 year of consent)
• Taking a stable regimen of disease-modifying therapy (DMT) prior to informed consent. If intermediate-potency DMT, the DMT must have been started and maintained for at least two years prior to consent. If high-potency DMT, the DMT must have been started and maintained at least one year prior to consent.
• Score of 2.5 to 6.0 by Expanded Disability Status Scale (EDSS) at baseline, with at least of 2 on the functional systems pyramidal function.

Exclusion Criteria:

• Confounding ophthalmologic disease or impairments/conditions that could interfere with visual testing (e.g., cataracts, disc hemorrhage, macular star, cotton wool spots, macular degeneration, glaucoma, diabetic and/or hypertensive retinopathy, history of detached retina, etc.)
• Severe myopia defined as a refractive error of -6.00 diopters or more
• Concurrent neurological disorders, including known moderate or severe cervical myelopathy.
• Clinical optic neuritis within 6 months before screening.
• Documented optic neuritis in the qualifying eye greater than 5 years before screening.
• Steroid treatment for MS symptoms in the 30 days prior to consent
• Hypersensitivity/allergy to MRI contrast agents and/or unable to perform MRI (e.g., claustrophobia).
• Regular use of or dependency on nicotine products within the past year.
• Not a surgical candidate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Active stimulation for 1 minute once per day	Procedure: Procedure/Surgery: Implant Procedure; The SetPoint System (study device)contains a miniaturized stimulator (implnat) 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.; Drug: Disease-Modifying Therapies (DMTs); All subjects will continue treatment with standard of care disease-modifying therapies for he duration of the study.; Device: Device: Active stimulation; Active stimulation for 1 minute once per day
Sham Comparator: Control; Non-active stimulation for 1 minute once per day	Procedure: Procedure/Surgery: Implant Procedure; The SetPoint System (study device)contains a miniaturized stimulator (implnat) 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.; Drug: Disease-Modifying Therapies (DMTs); All subjects will continue treatment with standard of care disease-modifying therapies for he duration of the study.; Device: Device: Non-active stimulation; Non-active stimulation for 1 minute once per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	All adverse events from Screening through Week 96 (end of study) will be tabulated.	Informed consent through Week 96

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in VEP latency	Change from baseline full-field VEP P100 latency at Week 48.	Baseline (Screening) through Week 48
Change in lesion size as detected on MRI	New T2 and/or contrast enhancing lesions Change in T2 lesion volume Change in phase (paramagnetic) rim lesions (PRL) Difference in the occurrence and volume of slowly expanding lesions	Baseline (Screening) through Week 48
Change in number of letters accurately read	Change from baseline in LCLA and HCVA at Week 48.	Baseline (Screening) through Week 48
Change in the NEI-VFQ-25 score	Change from baseline in NEI-VFQ-25 at Week 48	Baseline (Screening) through Week 48
Change in EDSS scores	Change from baseline in EDSS at Week 48	Baseline (Screening) through Week 48
Change in Modified MSFC scores	Change from baseline in modified MSFC at Week 48 for both composite score and each individual assessment (25-foot timed walk, 9-hole peg, and Symbol Digit Modalities Test)	Baseline (Screening) through Week 48
Change in MFIS score	Change from baseline in MFIS at Week 48	Baseline (Screening) through Week 48
Change in magnetization transfer ratios (MTR) in brain lesions	MTR is a surrogate to detect remyelination of lesions in the brain.	Baseline (Screening) through Week 48

Collaborators and Investigators

• Sponsor: SetPoint Medical Corporation

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): September 30, 2030

Study Registration Dates

• First Submitted: January 22, 2025
• First Submitted That Met QC Criteria: January 22, 2025
• First Posted (Actual): January 28, 2025

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: SPM-040

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: Yes