Noninvasive Vagal Nerve Stimulation (VANISH-MS)

Noninvasive Vagal Nerve Stimulation for the Management of Symptoms Experienced in Multiple Sclerosis (VANISH-MS): An Open-Label Home-Based Study of taVNS and tcVNS Compared to tDCS

Growing evidence suggests that vagal nerve stimulation (VNS) may be novel and effective in the management of the symptom burden of multiple sclerosis (MS) potentially by reducing inflammation and emotional distress, therefore improving overall well-being.

We will complete a pilot study comparing transcutaneous auricular vagus nerve stimulation (taVNS) and transcutaneous cervical vagus nerve stimulation (tcVNS) to a standard intervention of dorsolateral prefrontal cortex (DLPFC) transcranial direct current stimulation (tDCS) as an active control. The primary outcome will be feasibility and the preliminary efficacy data concerning self-reported symptom reduction to inform the design of an intervention, and estimated power needed to complete a larger sham-controlled RCT. We will also measure heart rate variability (HRV), an easily obtained biomarker of vagus nerve stimulation (VNS), in correspondence to intervention response.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Device: Remotely Supervised Transcranial Direct Current Stimulation (RS - tDCS); Device: Remotely Supervised Transcutaneous Auricular Vagus Nerve Stimulation (RS - taVNS); Device: Remotely Supervised Transcutaneous Cervical Vagus Nerve Stimulation (RS - tcVNS)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shayna Pehel; Phone Number: 929-455-5104; Email: Shayna.Pehel@nyulangone.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10017
      • Recruiting
      • NYU Langone Health
      • Principal Investigator: Leigh Charvet, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Female
• Age 25-65 years (inclusive)
• Definite diagnosis of MS or related demyelinating disorders (e.g., Neuromyelitis Optica or NMO)
• Stable high efficacy DMT ≥ 6 months before enrollment and throughout the trial
• PDDS score ≤ 6 (established to be able to complete procedures)
• SymptoMScreen Score ≥12
• WRAT-5 ≥85
• SDMT z-score > -3.0
• K10 < 35
• Stable disease activity, defined as being more than 1 month after a clinical relapse or confirmed radiologic disease activity, or more than 1 month after steroid treatment
• Ability to use mobile devices

Exclusion Criteria:

• Primary neurologic disorder other than MS and related demyelinating disorders like NMO (e.g., stroke, Parkinson's disease, spinal cord injury, intracranial mass, traumatic brain injury (TBI), epilepsy, mild cognitive impairment (MCI), or dementia), psychiatric disorders or major medical disorders (e.g., history of myocardial infarction, diabetes, thyroid disease, arrhythmia, atrial fibrillation)
• Diagnosis of Postural Orthostatic Tachycardia Syndrome (POTS)
• History of vagus nerve surgery/vagotomy
• History of diagnosed cardiovascular disease, a heart transplant, presence of permanent pacemaker implant or Left Ventricular Assist Device
• Use of certain medications that can affect heart rate variability, such as beta-blockers, calcium channel blockers, and cardiac glycosides
• Use of SP1 inhibitor medications such as Fingolimod, Siponimod, Ozanimod, and Ponesimod
• Nicotine use in the past 6 months (smoking/vaping)
• Pregnant or planning pregnancy during the study period or breastfeeding
• Seizure disorder or recent (<5 years) seizure history
• Active ear infections or ear pathology
• Current presence of implanted vagus nerve stimulator or any other active implanted electronic devices (e.g., pacemaker, defibrillators, cochlear implants, DBS, iVNS, etc.)
• Presence of metal objects in the head/neck
• Any skin disorder or skin sensitive area near stimulation locations
• BMI ≥ 35

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active DLPFC tDCS; 20 daily 20-minute sessions of active tDCS.	Device: Remotely Supervised Transcranial Direct Current Stimulation (RS - tDCS); tDCS is a noninvasive brain stimulation device that modulates brain activity delivering a low-intensity electrical current.
Experimental: Active taVNS; 20 daily 60-minute sessions of active taVNS.	Device: Remotely Supervised Transcutaneous Auricular Vagus Nerve Stimulation (RS - taVNS); taVNS is a noninvasive peripheral nerve stimulation device that modulates vagus nerve activity delivering a low-intensity electrical current (< 5mA) through hydrogel electrodes to the left auricular branch of the vagus nerve.
Experimental: Active tcVNS; 20 daily 20-minute sessions of active tcVNS.	Device: Remotely Supervised Transcutaneous Cervical Vagus Nerve Stimulation (RS - tcVNS); tcVNS is a noninvasive peripheral nerve stimulation device that modulates vagus nerve activity delivering a low-intensity electrical current (< 5mA) through cervical hydrogel electrodes to the left cervical branch of the vagus nerve.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants who Complete Home-Based taVNS or tcVNS Sessions	Assessed among participants in the taVNS or tcVNS arms only.	Up to Week 4 (End of Intervention)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in SymptoMScreen Score	SymptoMScreen is a self-report tool to assess overall symptom burden.	Baseline, Week 4 (End of Intervention)
Change in Multiple Sclerosis Impact Scale (MSIS-29) Score	12-item self-report scale to assess symptom burden regarding neurological domains and the psychological impact of MS. Each item is rated on a 7-point Likert scale from 0 to 6. The item responses are summed to calculate a total score ranging from 0 to 72, with a higher score indicating more severe symptom limitations	Baseline, Week 4 (End of Intervention)
Change in Memorial Symptom Assessment Scale (MSAS) Score	32-item symptom self-report rating scale to better understand the symptom severity, symptom frequency, and distress from common symptoms. The total MSAS score is the average of the symptom scores for all 32 symptoms and ranges from 0 to 4. Higher scores indicate greater impact from symptoms.	Baseline, Week 4 (End of Intervention)
Change in Kessler Psychological Distress Scale (K10) Score	10-item questionnaire to assess psychological distress over a recent period of the past 4 weeks focusing on anxiety and depressive symptoms. Each item is rated on a 5-point Likert scale from 1-5. The total score is the sum of responses and ranges from 10-50; higher scores indicate more severe mental disorder.	Baseline, Week 4 (End of Intervention)
Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance - Short Form Score	8-item qualitative self-report questionnaire regarding functions of sleep and wakefulness such as perceived sleep quality, sleep depth, and restfulness after sleep in the past 7 days. Each item is rated on a scale from 1-5. The total score is the sum of responses and ranges from 8-40; a higher score indicates more severe sleep disturbances.	Baseline, Week 4 (End of Intervention)
Change in PROMIS Fatigue - Short Form 7a Score	7-item self-report tool assessing fatigue severity and impact. Each item is rated on a scale from 1-5. The total score is the sum of responses and ranges from 7-35; higher scores indicate greater fatigue.	Baseline, Week 4 (End of Intervention)
Change in PROMIS Pain Intensity - Short Form 3a Score	3-item tool to evaluate quantitative participant experiences of pain intensity both over the past 7 days and at the time of completing the self-report assessment. Each item is rated on a scale from 1-5. The total score is the sum of responses and ranges from 3-15; higher scores indicate greater pain intensity.	Baseline, Week 4 (End of Intervention)
Change in General Anxiety Disorder (GAD-7) Score	7-item self-report questionnaire to screen for generalized anxiety in addition to assessing severity of anxiety symptoms. Each item is rated on a scale from 0 (not at all) to 3 (nearly every day). The total score is the sum of responses and ranges from 0-21; higher scores indicate more prevalent symptoms of anxiety.	Baseline, Week 4 (End of Intervention)
Change in Composite Autonomic Symptom Score-31 (COMPASS-31) Score	31-item scale measuring autonomic symptoms in six domains: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor functions. A total score from 0-100 is generated from the item responses; higher scores indicate more severe autonomic dysfunction.	Baseline, Week 4 (End of Intervention)
Change in Patient Health Questionnaire (PHQ-9) Score	9-item self-report questionnaire to screen for depressive disorder and furthermore, severity. Each item is rated on a scale from 0 (not at all) to 3 (nearly every day). The total score is the sum of responses and ranges from 0-27; higher scores indicate greater severity of depressive symptoms.	Baseline, Week 4 (End of Intervention)
Change in Nine-Hole Peg Test (9HPT) Score	Assessment of manual dexterity and fine motor coordination in people with MS, using both dominant and non-dominant hands. The score is measured by the number of seconds it takes for a person to place and remove nine pegs from a pegboard, with a lower score (in seconds) indicating better dexterity and faster completion time.	Baseline, Week 4 (End of Intervention)
Change in Heart Rate Variability (HRV)	Assessed using the Chest Strap Polar H10 HR sensor.	Baseline, Week 4 (End of Intervention)

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Leigh Charvet, PhD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2025
• Primary Completion (Estimated): February 5, 2026
• Study Completion (Estimated): May 5, 2026

Study Registration Dates

• First Submitted: February 4, 2025
• First Submitted That Met QC Criteria: February 7, 2025
• First Posted (Actual): February 10, 2025

Study Record Updates

• Last Update Posted (Estimated): August 26, 2025
• Last Update Submitted That Met QC Criteria: August 25, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; tDCS; Neuromodulation; Vagus Nerve Stimulation; VNS; Home-Based
• 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
• Other Study ID Numbers: 24-01628

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share IPD.

Drug and device information, study documents

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