Transcutaneous Vagus Nerve Stimulation for Motor Recovery After Stroke

Safety and Effectiveness of Transcutaneous Vagus Nerve Stimulation Therapy to Improve Motor Recovery After Stroke

This study will evaluate the safety and effectiveness of Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) for improving motor recovery after stroke. Subacute stroke patients will receive RAVANS or sham stimulation concurrent with arm motor training during 10 intervention sessions occurring daily for 30 minutes over 2 weeks. The safety and improvements in arm motor function after the intervention will be compared in patients receiving RAVANS to those receiving sham stimulation.

Study Overview

• Status: Terminated
• Conditions: Stroke; Upper Extremity Paresis
• Intervention / Treatment: Device: Active RAVANS concurrent with arm motor training; Device: Inactive RAVANS concurrent with arm motor training

Detailed Description

This study will evaluate the safety, feasibility and effectiveness of Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) for improving motor recovery after stroke. Subacute stroke patients will be randomized to RAVANS or sham stimulation groups. Patients will receive RAVANS or sham stimulation concurrent with arm motor training during 10 sessions occurring daily for 30 minutes over 2 weeks. Safety will be compared in patients receiving RAVANS to those receiving sham stimulation. Feasibility will be evaluated by recruitment into the study and retention of enrolled patients. Changes in arm motor function will be compared between RAVANS and sham stimulation groups from baseline to immediately after the intervention period and to function at 3-months after stroke.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02129
      • Spaulding Rehabilitation Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Supratentorial ischemic or hemorrhagic stroke incurred 4-30 days prior;
• Contralesional UL motor impairment defined by NIHSS item 5 score 1 or 2 (scale 0-4);
• Age ≥ 18;
• Able to provide written informed consent.

Exclusion Criteria:

• Implanted electronic device (e.g., pacemaker, neurostimulator);
• Pregnancy;
• Major psychiatric or medical condition that could interfere with study participation;
• Medical condition affecting left ear that could interfere with delivering RAVANS (e.g., wound, infection, malignancy, hypoesthesia);
• Significant pre-existing disability of stroke-affected UL in activities of daily living due to prior stroke or other medical cause defined by Stroke Impact Scale item 7 (SIS-hand) mean score < 4 (scale: 0-5);
• History of seizure during year before stroke or > 1 post-stroke seizure;
• Significant cognitive or language impairment that would interfere with informed consent or study participation;
• Severe dysphagia;
• Bradycardia defined as resting heart rate < 50 bpm;
• Nonsustained ventricular tachycardia;
• Cardiac conduction disorder (i.e., bundle branch block, heart block, long Q-T syndrome);
• History of asystole;
• History of recurrent vaso-vagal syncope;
• Hypotension defined as blood pressure < 90/60 mmHg.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham stimulation	Device: Inactive RAVANS concurrent with arm motor training; Patient does not receive stimulation delivered to the skin of left outer ear while participating in arm motor training
Experimental: RAVANS	Device: Active RAVANS concurrent with arm motor training; Patient receives non-painful, sensory-level stimulation to the skin of left outer ear, where nerve endings of the auricular branch of the vagus nerve reside, while participating in arm motor training

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Upper extremity motor impairment	Change in upper extremity subtest of Fugl Meyer Assessment (FMA-UE) score	Baseline to just after 10 intervention sessions, and baseline to 3 months post-stroke

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Upper extremity motor function	Change in Action Research Arm Test (ARAT) score	Baseline to just after 10 intervention sessions, and baseline to 3 months post-stroke
Grip force control	Change in accuracy, variability and temporal structure of performance on a grip force control task	Baseline to just after 10 intervention sessions, and baseline to 3 months post-stroke
Upper extremity disability	Change in hand subtest of Stroke Impact Scale (SIS-hand) score	Baseline to 3 months post-stroke
Mood state, anxiety and depression	Change in Hospital Anxiety and Depression Scale (HADS) scores	Baseline to 3 months post-stroke

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Dana Foundation, Spaulding Rehabilitation Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2018
• Primary Completion (Actual): November 20, 2018
• Study Completion (Actual): November 20, 2018

Study Registration Dates

• First Submitted: September 20, 2017
• First Submitted That Met QC Criteria: September 22, 2017
• First Posted (Actual): September 25, 2017

Study Record Updates

• Last Update Posted (Actual): September 21, 2021
• Last Update Submitted That Met QC Criteria: September 14, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: stroke; vagus nerve stimulation; upper extremity paresis
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Stroke; Muscle Weakness; Paresis
• Other Study ID Numbers: 2017P000129

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No