Non-invasive VNS in Stroke Recovery

NCT ID: NCT06761404

Last Updated: 2025-05-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-15
• Study Completion Date: 2028-06-01

Brief Summary

To evaluate feasibility and effectiveness of non-invasive VNS to enhance stroke recovery

Detailed Description

In this study, (Aim 1) we will test whether our non-invasive trans-auricular vagus nerve stimulation (taVNS) during occupational therapy task performance has the potential for large scale application through superior clinical benefit compared to sham in a broad group of stroke survivors including hemorrhagic strokes.

To determine the predictors of effective brain rewiring in the individual stroke patient, we will use an EEG and/or functional MRI (fMRI) connectivity biomarker independently of the success of the stimulation paradigm (Aim 2). We will test the hypothesis that better motor function will be associated with increased motor network connectivity pattern.

The central objective of this application is to determine whether taVNS significantly improves motor recovery for both ischemic and hemorrhagic strokes through increased connectivity as measured by a biomarker of plasticity. We address our objective through the following aims:

Aim 1: To determine the extent to which taVNS with concurrent occupational therapy (OT), causes significant, lasting motor gains in chronic stroke population

Hypothesis A: More chronic stroke patients treated with taVNS+OT will show clinically meaningful improved hand motor function over Sham+OT immediately after treatment as measured by upper extremity Fugl-Meyer (uFM) test response rate. 60 patients at least 6 months after ischemic or hemorrhagic stroke with persistent arm weakness will be enrolled in a 6-week double masked, sham-controlled, balanced parallel group design phase 2 clinical trial.

Hypothesis B: The sham group will achieve the same degree of motor function improvement in the open label cross-over phase as the original active taVNS group sustained clinical improvement after OT+VNS.

Hypothesis C: The open label home extension taVNS+OT phase will produce additional motor function improvement and will be associated with improved patient and caregiver satisfaction.

Aim 2: To determine the induced connectivity pattern of the brain resulting in the improved motor performance

Hypothesis A: Chronic stroke patients with improved motor performance will demonstrate increased connectivity between motor cortical areas as measured by high-definition EEG and/or fMRI functional connectivity compared to the non-responders immediately after treatment.

Hypothesis B: Network activation with taVNS is dependent on timing compared to movement and stimulation intensity. We will perform fMRI and /or high-definition EEG to evaluate network activity during taVNS at different intensity and phase of the movement.

This study evaluates the feasibility, efficacy and underlying plasticity changes of adjuvant noninvasive VNS to enhance motor recovery following ischemic and hemorrhagic strokes.

Conditions

Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sham Stimulation

Same procedure as with the active stimulation using the device's sham settings to elicit the same cutaneous sensation as the other stimulation conditions..

Group Type: SHAM_COMPARATOR

taVNS

Intervention Type: DEVICE

Experimental. The current will be increased gradually for both sham and real stimulation at the beginning of the 90-minute stimulation to lessen the itchy/numb skin sensation and to create the same skin sensation for subject blinding.

taVNS

Weak current (up to 0.8-4 mA) will be delivered using pulses according to standard protocol during each motor task for up to 90-minutes through surface electrodes which will be administered using the intensity identified as resulting in well tolerated skin sensation and best motor performance during our initial testing session.

Group Type: EXPERIMENTAL

taVNS

Intervention Type: DEVICE

Experimental. The current will be increased gradually for both sham and real stimulation at the beginning of the 90-minute stimulation to lessen the itchy/numb skin sensation and to create the same skin sensation for subject blinding.

Interventions

taVNS

Experimental. The current will be increased gradually for both sham and real stimulation at the beginning of the 90-minute stimulation to lessen the itchy/numb skin sensation and to create the same skin sensation for subject blinding.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Symptomatic ischemic or hemorrhagic stroke verified by computerized axial tomography or magnetic resonance imaging resulting in hemiparesis (MRC 1-4).
• Age more than 18, Male or Female, All racial and ethnic groups
• Entry into the study >6 months post onset
• Patients who can safely undergo taVNS
• Able to follow 2 step commands
• Modified Ashworth Scale Score =<3 in the involved upper extremity
• Passive range of motion within functional ranges at the shoulder, elbow, wrist and hand
• UFM =< 60 (scale 0-66)

Exclusion Criteria

• Patients with history of severe alcohol or drug abuse, psychiatric illnesses like severe depression, poor motivational capacity, or severe language disturbances, particularly of receptive nature or with serious cognitive deficits (defined as unable to follow study instructions).
• Patients with bilateral paresis, or weakness or sensory damage due to peripheral causes (e.g. peripheral nerve injury, muscle or orthopedic injury etc.)
• Subjects with contraindication to MRI of the brain
• Patients with severe uncontrolled medical problems (e.g. cardiovascular disease, severe rheumatoid arthritis, active joint deformity of arthritic origin, active cancer or renal disease, any kind of end-stage pulmonary or cardiovascular disease, or a deteriorated condition due to age, epilepsy or others).
• Patients with unstable cardiac arrhythmia, reentry tachycardia.
• Pregnancy
• Patients with pacemakers or stimulators that interfere with the stimulation, or other investigational devices or drugs
• Non-English speaking individuals will only be eligible if they can provide the appropriate translator for all the sessions of the study as no funding is available to pay for such services. However we plan to include them once funding has been secured in the subsequent larger trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Methodist Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Timea Hodics

Director, Interventional Neuro-Recovery Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Timea Hodics, MD

Role: PRINCIPAL_INVESTIGATOR

The Methodist Hospital Research Institute

Locations

Houston Methodist Research Institute

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sergio Ibarra Cortez, MD

Role: CONTACT

shibarracortez@houstonmethodist.org

346-238-2494

Rachel Markley, MPH

Role: CONTACT

rmarkley@houstonmethodist.org

7134413770

Facility Contacts

Rachel Markley

Role: primary

rmarkley@houstonmethodist.org

713-441-3770

Other Identifiers

PRO00038365

Identifier Type: -

Identifier Source: org_study_id