Non-invasive VNS in Stroke Recovery

The Methodist Hospital Research Institute60 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Stroke

Interventions

taVNSDEVICE

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (1)

Houston Methodist Research Institute

Houston, Texas, United States

RECRUITING

Outcomes

Primary Outcomes

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

To determine the extent to which taVNS with concurrent occupational therapy (OT), causes significant, lasting motor gains in chronic stroke population Upper extremity Fugl-Meyer (uFM) The uFM test measures both proximal and distal upper extremity movements, ranges 0-66, higher score is better.

Time frame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]

Secondary Outcomes

To evaluate the biomarkers of plasticity associated with VNS

We will use an EEG and/or functional MRI (fMRI) connectivity biomarker.

Time frame: [Time Frame: Baseline 1(week 1), post-intervention (week 6), post intervention for sham crossover only (week 12)]

Wolf Motor Function Test (WMFT)

The WMFT is a time-based method to evaluate upper extremity performance while providing insight into joint-specific and total limb movements. This measurement includes video recording of the task performance where de-identifying will be attempted to the degree possible (face not in the frame, removing/blocking out identifying jewelry etc.). All patients will sign an informed consent explicitly authorizing such video-recording.

Time frame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]

Functional upper extremity levels (FUEL)

The FUEL is an upper extremity post-stroke motor function classification system that does not require significant extra time or evaluator training.

Time frame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]

NIH STROKE SCALE (NIHSS)

The NIHSS is a standardized clinical examination to evaluate clinical functional impairment after stroke.

Central Contacts

Darrel W Cleere, MPH

CONTACT

7134413770 dwcleere@houstonmethodist.org

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.