Stroke, Chronic, Upper Extremity Paresis
Conditions
Brief summary
This is a single-center, multiphase pilot study of 16 subjects with residual upper extremity deficits at least six months after a supratentorial ischemic or hemorrhagic stroke. The purpose of the study is to evaluate the clinical safety, device functionality, and treatment effect of non-invasive electrical stimulation of the trigeminal and/or vagus nerves (nTVNS) using the NeuraStasis Stimulator System adjunctive to rehabilitation. Phase 1 consisted of 5 unblinded subjects receiving nTVNS to assess device usability and safety. Phase 2 used a Prospective Randomized Open, Blinded Endpoint (PROBE) design comparing nTVNS to sham stimulation in 11 subjects. The study will inform the design and implementation of a pivotal study.
Detailed description
This pilot study proceeded in two phases: Phase I, an unblinded stage, and Phase II, a blinded stage comparing intervention and sham groups. Phase I consisted of 5 subjects, unblinded, receiving nTVNS. This phase tested the usability of the device and de-risked the use of nTVNS during rehabilitation. Visits included consent and baseline evaluation, followed by 6 weeks of treatment consisting of upper extremity rehabilitation paired with nTVNS. Rehabilitation and treatment occurred at a cadence of 3 sessions per week. Primary endpoints was collected after 6 weeks. Phase II consisted of a Prospective Randomized Open, Blinded Endpoint (PROBE) design with 11 subjects randomized to an intervention nTVNS group or a control sham stimulation group. Both groups received a stimulation tolerability assessment at the start of each session to support blinding for therapists and subjects. For the sham group, no stimulation was delivered during the priming or rehabilitation portions of the session. The same evaluations, sessions, and endpoints occurred as those in Phase 1.
Interventions
DEVICENeuraStasis Stimulator System (Non-Invasive Trigeminal and Vagus Nerve Stimulation)
Pulsed electrical stimulation of the trigeminal and vagus nerves paired with upper limb rehabilitation movements
Rehabilitation movements to improve upper limb function after stroke
OTHERSham Stimulation
Control sham stimulation of the trigeminal and vagus nerves is delivered at the start of each session. Performed alongside standard-of-care rehabilitation.
Sponsors
NeuraStasis, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* History of unilateral supratentorial ischemic, intracerebral hemorrhagic, subarachnoid hemorrhagic, or a heterogeneous lesion stroke that occurred at least 6 months but not more than 15 years prior to enrollment. * Age \>30 years and \<85 years. * Fugl-Meyer Assessment, Upper Limb (FMA-UE) baseline score of 10 to 56 (inclusive of 10 and 56). * Ability to communicate, understand, and provide appropriate consent. Subjects should be able to follow two-step commands. * Right- or left-sided weakness of the upper extremity.
Exclusion criteria
* Participant with any implanted metallic device at or near the stimulation sites (forehead and ears). * Participant with an implanted or active stimulator (ex. Deep brain stimulator, pacemaker, vagus nerve stimulator, defibrillator) * Participant skin in the stimulation area has open wounds, skin eruptions, swollen, infected, or inflamed areas, or skin abnormalities that could be cancerous * Advanced cardiac, pulmonary, liver, kidney dysfunction or blood system disease * Participant has a fever or shows clinical signs concerning for an infectious disease * Other neurologic or musculoskeletal diseases that could interfere with the assessments of this study * Low heart rate (\<60 bpm) from a cardiac conduction block or related etiology * Participant has a history of trigeminal neuralgia * Participant has a history of Bell's Palsy * History of cranial nerve neuropathy (including facial nerve injury), carotid surgery, vagotomy, or other surgical intervention on the vagus nerve * History of recurrent syncopal events * Known or newly-discovered aneurysm or arteriovenous malformation * Patients who have any terminal illness such that the patient would not be expected to survive more than 90 days * Botox injections 12 weeks prior to or during therapy * Participants who have had a craniectomy: * Without replacement of bone flap * With bone flap replaced \< 6 months prior to initiation of study activities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fugl-Meyer Assessment, Upper Limb (FMA-UE) Average Change | Within 7 days of completing 6 weeks of rehabilitation | The Fugl-Meyer Assessment, Upper Limb (FMA-UE) will be analyzed for the difference in average change after 6 weeks of therapy compared to baseline. The FMA-UE is a common scale used to measure motor impairment after a stroke. The range is 0 (more impairment) to 66 (no impairment). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Action Research Arm Test (ARAT) Average Change | Within 7 days of completing 6 weeks of rehabilitation | The ARAT will be analyzed for the difference in average change after 6 weeks of therapy compared to baseline. The ARAT is a widely used clinical scoring tool for stroke rehabilitation. The test consists of 19 items that are grouped into four sub-tests: grasp, grip, pinch, and gross movement. The total score on the ARAT ranges from 0 to 57, with a higher score indicating better performance. |
| Fugl-Meyer Assessment, Upper Limb (FMA-UE) Response % | Within 7 days of completing 6 weeks of rehabilitation | The FMA-UE will be analyzed for the % of subjects that responded to treatment defined as achieving an effect equivalent to a greater than the minimal clinically important difference. |
| Proportion of subjects completing all pre-specified treatment doses | Upon completion of 6 weeks of rehabilitation | Proportion of subjects completing all pre-specified treatment sessions across the 6 weeks of rehabilitation |
| Subject Questionnaire on Device Usage | Upon completion of 6 weeks of rehabilitation | A questionnaire that evaluates subjects' level of comfort during use of the device on a 5-point scale, with 5 being the most comfortable and 1 being the least comfortable. |
| Therapist Questionnaire on Device Usage | Upon completion of 6 weeks of rehabilitation | A questionnaire that evaluates the ease of use of the device by therapists during the administration of rehab with the device on a 5-point scale, with 5 being the most usable and 1 being the least usable. |
| Serious adverse device effects (SADE) rate at 24 hours post-therapy session | Up to 24 hours after each therapy session and ending 24 hours post-last therapy session at 6 weeks of rehabilitation | SADE rate at 24 hours post-therapy sessions |
| Stroke impact scale (SIS) Domain and Summative Score Average Change | Within 7 days of completing 6 weeks of rehabilitation | The Stroke Impact Scale (SIS) is a multidimensional self-reported measure of health-related quality of life. The SIS includes 59 items and assesses 8 domains: strength (four items), memory and thinking (seven items), emotion (nine items), communication (seven items), activities of daily living (ten items), mobility (nine items), hand function (five items) and participation and function in life activities (ten items). Each item is rated using a 5-point Likert-type scale (1 = an inability to complete the item; 5 = no difficulty experienced at all) and a global score is calculated as a summative score of each domain, transformed into a 0-100 scale. It includes an extra question on the person´s perceived stroke recovery measured in the form of a visual analogue scale from 0-100. Individual domain scores and the summative score will be analyzed for the difference in average change after 6 weeks of therapy compared to baseline. |
| Analysis of the number of stimulations per therapy session | Collected at each therapy session across 6 weeks of rehabilitation | The number of paired stimulations initiated each rehabilitation session will be analyzed to understand personalized effectiveness and responder likelihood. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSean Savitz, MD
The University of Texas Health Science Center, Houston
STUDY_DIRECTORKirt Gill, MD
NeuraStasis, Inc
Outcome results
None listed