Clinical trial NCT06761404: Non-invasive VNS in Stroke Recovery
Official title: Non-invasive VNS in Stroke Recovery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Stroke
Keywords: taVNS
trans-auricular
non-invasive vagus nerve stimulation
stroke recovery
neuromodulation
rehabilitation
chronic stroke
Lead sponsor: The Methodist Hospital Research Institute
Sponsor class: OTHER
First posted: 2025-01-07
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Sham stimulation vs taVNS
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: To evaluate feasibility and effectiveness of non-invasive VNS to enhance stroke recovery
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]
Secondary outcomes:
measure: To evaluate the biomarkers of plasticity associated with VNS
timeFrame: [Time Frame: Baseline 1(week 1), post-intervention (week 6), post intervention for sham crossover only (week 12)]
measure: Wolf Motor Function Test (WMFT)
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]
measure: Functional upper extremity levels (FUEL)
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]
measure: NIH STROKE SCALE (NIHSS)
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]. Max score 42, minimum score 0. Score of 0 is best outcome
measure: MRC grading scale
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]. Minimum score 0, max score 5 per item. 5 is normal, 0 is no movement.
measure: Timed up and Go
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]
measure: Barthel Index (BI)
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]. Minimum score 0, maximum score 100. Higher score is better
measure: Stroke Impact Scale (SIS)
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]. Minimum score 0, maximum score 100. 0 means no recovery, 100 means fully recovered
measure: Zarit Burden Interview: Short (12-items)
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]
measure: Modified Rankin Scale (mRS)
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]
measure: Modified Ashworth Spasticity Scale
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]
measure: Quick Inventory of Depressive Symptomatology, Self-report (QIDS-SR)
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]. Minimum score 0, maximum score greater than 21. 0-5 means normal, greater than 21 is not
measure: taVNS questionnaire
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]
measure: Motor Activity log
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]
measure: Wrist flexion-extension measurement
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]
measure: To determine the taVNS induced connectivity pattern of the brain
timeFrame: [Time Frame: Baseline, post intervention (week 6), post intervention (week 12), and follow up for the sham crossover group (week 18)]
Other outcomes:
Locations:
city: Houston
country: United States
facility: Houston Methodist Research Institute
state: Texas
Study officials:
affiliation: The Methodist Hospital Research Institute
name: Timea Hodics, MD
role: PRINCIPAL_INVESTIGATOR
References: