Cranial Nerve Neuromodulation to Improve Arm Function and Brain Plasticity in Stroke

NCT06386510 | Recruiting DMC

• 1 other identifier: 2025-5517
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 3

Brief Summary

Following a stroke, persistent residual muscle weakness in the upper limb (UL) drastically impacts the individuals' quality of life and level of independence. Training interventions are recommended to promote UL motor recovery, and recent studies have shown that training must be tailored to each individual's recovery potential to maximise training gains. Complementary to training interventions, non-invasive brain stimulation devices (NIBS) can help support the provision of post-stroke care by modulating brain excitability and enhancing recovery. Among NIBS, cranial nerve non-invasive neuromodulation (CN-NINM) is gaining increasing attention in rehabilitation since it can directly and non-invasively stimulate the tongue's cranial nerves. The impulses generated can then reach the motor cortex, induce neuroplastic changes and support recovery. Promising results in various neurological populations have been observed, but in stroke, the efficacy of CN-NINM at improving arm motor recovery and brain plasticity is yet to be determined. This is what the present project intends to address, using a stratified randomized controlled trial, where participants in the chronic phase of a stroke will take part in a 4-week individualized training program of their affected UL in combination with real or sham CN-NINM. Before and after the intervention, participants will undergo clinical and neurophysiological evaluations to thoroughly evaluate CN-NINM-induced changes in UL motor function and associated neuroplastic changes. The proposed study will allow an in-depth evaluation of the effects of CN-NINM for an eventual implementation in clinics and at home to support optimal post-stroke recovery.

Conditions

Stroke

Keywords

Cranial nerve non-invasive neuromodulation; Brain plasticity; Recovery; Strength training; Transcranial magnetic stimulation

Outcome Measures

Primary Outcomes (3)

• Change in UL motor function on the Fugl-Meyer Stroke Assessment Scale

  Change in motor function of the affected UL will be assessed using the Fugl-Meyer Stroke Assessment. The score of this scale range from 0 (no motor recovery) to 66 (full motor recovery).

  The assessments will be done at the baseline and in the week after completion of the training program and CN-NINM

• Change in UL functional performance on the Wolf Motor Function Test

  Change in functional performance of the affected UL will be assessed with the timed score of the Wolf Motor Function Test; comprising 17 tasks. The maximal time allocated to each task is 120 seconds.

  The assessments will be done at the baseline and in the week after completion of the training program and CN-NINM.

• Change in motor cortex excitability by means of resting MEP amplitudes elicited by TMS over both hemispheres.

  Change in motor cortex excitability will be assessed by resting peak-to-peak MEP amplitudes of the affected and unaffected first dorsal interosseous muscles (FDI) at 130% of the FDI resting motor threshold over 20 trials

  The assessments will be done at the baseline and in the week after completion of the training program and CN-NINM.

Secondary Outcomes (3)

• Change in participants' subjective real life functional UL performance on the Motor Activity Log

  The assessments will be done at the baseline and in the week after completion of the training program and CN-NINM.

• Change in active and passive range of motion at both UL in shoulder flexion, elbow flexion and wrist extension

  The assessments will be done at the baseline and in the week after completion of the training program and CN-NINM.

• Change in resting motor threshold of the affected and unaffected FDI

  The assessments will be done at the baseline and in the week after completion of the training program and CN-NINM.

Study Arms (2)

real CN-NINM + UL training group

EXPERIMENTAL

Upper limb strength training program combined to real CN-NINM

Procedure: Strength training; Procedure: Cranial nerve non-invasive neuromodulation

sham CN-NINM + UL training group

PLACEBO COMPARATOR

Upper limb strength training program combined to sham CN-NINM

Procedure: Strength training; Procedure: Cranial nerve non-invasive neuromodulation

Interventions

Strength training PROCEDURE

The strength training program will last 4 weeks (3 X/week, 60 minutes). Using dead weights, the 1RM (i.e. the maximal load that an individual can lift once) will be estimated by the 10RM for the wrist extensors and the elbow and shoulder flexors. The grip muscles of the affected hand will also be trained with a JAMAR® dynamometer. Depending on each participant's intensity training group, training will start at 35%, 50% or 70% of 1RM and will be increased by 5% each week to reach, by week 4, 50%, 65% and 85%, for the low, moderate, and high-intensity group, respectively.

real CN-NINM + UL training group; sham CN-NINM + UL training group

Cranial nerve non-invasive neuromodulation PROCEDURE

For the first 20 minutes of each training session, CN-NINM will be applied (50 μsec at 150 Hz), using a portable stimulator (Cthulhu Shield, USA) with a network of 18 electrodes, directly on the participants' tongue. The participants will hold the device in place by pressing their tongue upwards and the intensity of the stimulus will be set by each participant to a comfortable level of sensation (experimental group) or set by a trainer to a non-perceivable stimulus (control group).

real CN-NINM + UL training group; sham CN-NINM + UL training group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• be ≥18 years of age;
• have had a unilateral supratentorial stroke;
• be in a chronic stage of recovery (\>6 months);
• present some UL motor recovery (Fugl-Meyer Stroke Assessment \[FMA-UE\] score ≥25/66);
• are not involved in rehabilitation treatments.

You may not qualify if:

• significant spasticity at UL (score \>3 on the modified Ashworth scale);
• major sensory deficit at UL (a score \<25/34 on the Nottingham sensory assessment and a score \<6 on the vibration threshold assessment);
• hemineglect (\> 70% of unshaded lines on the same side as the motor deficit on the Line Cancellation test);
• apraxia (score \>2.5 on the Alexander test);
• a neurological disorder other than stroke-related;
• orthopedic problems at UL;
• cognitive impairment (score \<2/5 on the Mini-Cog);
• significant pain intensity at UL (a score ≥ 6/10 on the Visual Analog Pain Scale);
• absence of MEP (peak-to-peak MEP amplitude \<20μV);
• contraindications to CN-NINM and TMS.

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Heart and Stroke Foundation of Canada: collaborator

Study Sites (3)

CRIR/Feil/Oberfeld Research Center; Centre intégré de santé et de services sociaux de Laval; Jewish Rehabilitation Hospital

Laval, Quebec, H7V 1R2, Canada

RECRUITING

CIRRIS

Québec, Quebec, G1M2S8, Canada

RECRUITING

Centre de recherche sur le vieillissement

Sherbrooke, Quebec, J1H 4C4, Canada

RECRUITING

MeSH Terms

Conditions

Stroke

Interventions

Resistance Training

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Marie-Helene Milot, PhD

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marie-Helene Milot, PhD

CONTACT

819-780-2220; marie-helene.milot@usherbrooke.ca

Maureen Ahiatsi, MsC

CONTACT

819-780-2220; maureen.rudy.sandra.ahiatsi@usherbrooke.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: multicentered stratified randomized controlled trial

Study Record Dates

• First Submitted: April 23, 2024
• First Posted: April 26, 2024
• Study Start: June 1, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: May 7, 2025

Record last verified: 2025-04

Locations

CA (3)