Wireless Nerve Stimulation Device To Enhance Recovery After Stroke

Sponsor

Baylor Research Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT04534556

Collaborator

The University of Texas at Dallas (Other), University of Texas Southwestern Medical Center (Other), National Institute of Neurological Disorders and Stroke (NINDS) (NIH)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Texas Biomedical Device Center (TxBDC) has developed an innovative strategy to enhance recovery of motor and sensory function after neurological injury termed targeted plasticity therapy (TPT). This technique uses brief pulses of vagus nerve stimulation to engage pro-plasticity neuromodulatory circuits during rehabilitation exercises. Preclinical findings demonstrate that VNS paired with rehabilitative training enhances recovery in multiple models of neurological injury, including stroke, spinal cord injury, intracerebral hemorrhage, and traumatic brain injury. Recovery is associated with neural plasticity in spared motor networks in the brain and spinal cord. Moreover, two initial studies and a recently completed Phase 3 clinical trial using a commercially available device demonstrates that paired VNS with rehabilitation is safe and improves motor recovery after stroke. The purpose of this study is to extend these findings and evaluate whether VNS delivered with the new device paired with rehabilitation represents a safe and feasible strategy to improve recovery of motor and sensory function in participants with stroke.

Condition or Disease	Intervention/Treatment	Phase
Stroke Chronic Stroke Upper Extremity Paresis Ischemic Stroke	Device: Active Vagus Nerve Stimulation Device: Placebo Vagus Nerve Stimulation	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Prospective, double blind, randomized placebo controlled, plus open-label extensionProspective, double blind, randomized placebo controlled, plus open-label extension

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Device Feasibility

Official Title:

Wireless Nerve Stimulation Device To Enhance Recovery After Stroke

Actual Study Start Date :

Sep 1, 2021

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Nov 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Immediate Start Vagus Nerve Stimulation group The Immediate Start VNS group will receive rehabilitation and active stimulation for 18 in-office sessions over the course of approximately six weeks during Phase 1. For Phase 2, all subjects will be provided with the option to participate in an open-label extension consisting of an additional 18 sessions of in-office rehabilitation with active VNS over the course of approximately six weeks. Additionally, participants may be provided with a system of rehabilitative devices to utilize at home.	Device: Active Vagus Nerve Stimulation Stimulation of the vagus nerve that is paired with upper limb rehabilitation. VNS stimulation as described in the current study consists of 0.5 second trains of 0.8 mA; 100 µsec biphasic pulses at 30 Hz. Stimulation trains are delivered only during rehabilitation. Other Names: VNS vagus nerve stimulation paired VNS
Placebo Comparator: Delayed Start Vagus Nerve Stimulation group The Delayed Start VNS group will receive equivalent rehabilitation with placebo stimulation for 18 in-office sessions over the course of approximately six weeks during Phase 1. For Phase 2, all subjects will be provided with the option to participate in an open-label extension consisting of an additional 18 sessions of in-office rehabilitation with active VNS over the course of approximately six weeks. Additionally, participants may be provided with a system of rehabilitative devices to utilize at home.	Device: Placebo Vagus Nerve Stimulation During Phase 1 of the study, the placebo group will receive a minimal amount of stimulation that fails to sufficiently activate the nerve, unknown to the participant and therapists. All participants will receive active stimulation during the Phase 2 open-label portion of the study. Other Names: placebo control

Arm

Intervention/Treatment

Experimental: Immediate Start Vagus Nerve Stimulation group

The Immediate Start VNS group will receive rehabilitation and active stimulation for 18 in-office sessions over the course of approximately six weeks during Phase 1. For Phase 2, all subjects will be provided with the option to participate in an open-label extension consisting of an additional 18 sessions of in-office rehabilitation with active VNS over the course of approximately six weeks. Additionally, participants may be provided with a system of rehabilitative devices to utilize at home.

Device: Active Vagus Nerve Stimulation

Stimulation of the vagus nerve that is paired with upper limb rehabilitation. VNS stimulation as described in the current study consists of 0.5 second trains of 0.8 mA; 100 µsec biphasic pulses at 30 Hz. Stimulation trains are delivered only during rehabilitation.

Other Names:

VNS

vagus nerve stimulation

paired VNS

Placebo Comparator: Delayed Start Vagus Nerve Stimulation group

The Delayed Start VNS group will receive equivalent rehabilitation with placebo stimulation for 18 in-office sessions over the course of approximately six weeks during Phase 1. For Phase 2, all subjects will be provided with the option to participate in an open-label extension consisting of an additional 18 sessions of in-office rehabilitation with active VNS over the course of approximately six weeks. Additionally, participants may be provided with a system of rehabilitative devices to utilize at home.

Device: Placebo Vagus Nerve Stimulation

During Phase 1 of the study, the placebo group will receive a minimal amount of stimulation that fails to sufficiently activate the nerve, unknown to the participant and therapists. All participants will receive active stimulation during the Phase 2 open-label portion of the study.

Other Names:

placebo

control

Outcome Measures

Primary Outcome Measures

Incidence of Adverse Events [Device Safety] [From Week 1 through study follow-up, approximately two years after the final session of rehabilitation]
Review of adverse events reported throughout the trial will be used to inform the potential risks associated with the ReStore system and provide a better understanding of risk/benefit analysis

Secondary Outcome Measures

ReStore Stimulation Successes [Weeks 6-11]
The percentage of stimulation attempts classified as 'Success' from the total number of stimulation attempts made will be calculated for each participant and the mean percent of successful attempts across all participants will be used as the outcome measure.
Upper-Extremity Fugl-Meyer Assessment (UEFM) [Weeks 1, 5, 12, 19, 20, 24, 32]
The UEFM Assessment is a sixty-six point assessment of mobility administered by a therapist designed to facilitate consistent collection and reporting of basic upper extremity findings. The endpoint will be: estimate the shift in UEFM assessment following active VNS
Wolf Motor Task Functional Ability Scale [Weeks 1, 5, 12, 19, 20, 24, 32]
The Wolf Motor Task Functional Ability Scale (WMFT-FAS) is a quantitative measure of upper extremity motor ability through timed and functional tasks. The task includes evaluation of dexterity, strength, and upper extremity function. Functional ability is measured on a 6-point ordinal scale (0-5) with a maximum total score of 75. The endpoint will be: estimate the shift in WMFT-FAS assessment following active VNS
Action Research Arm Test [Weeks 1, 5, 12, 19, 20, 24, 32]
The ARAT is a nineteen-item observational assessment of upper limb function. The areas of assessment include activities of daily living, coordination, dexterity, and upper extremity function. The endpoint will be: Estimate the shift in ARAT assessment following active VNS
Modified Rankin Scale [Weeks 1, 5, 12, 19, 20, 24, 32]
The Modified Rankin Scale (MRS) is a single item global outcomes rating scale that categorizes level of functional independence. The measure reflects ability to perform activities of daily living and functional mobility. The MRS is a 6 point scale with 0 being no disability and 5 being severe disability. A score of 6 indicates that the patient has expired. The endpoint will be: Estimate the shift in MRS assessment following active VNS
Quantitative Force and Range of Motion Assessment [Weeks 1, 5-20, 24, 32]
The Quantitative Force and Range of Motion Assessment form is a physical assessment of upper limb changes in force/torque as a result of VNS paired rehabilitation. The endpoints will be: 10% increase in finger pinch and flexion force following active VNS; 10% increase in wrist flexion and extension force following active VNS; 10% increase in wrist pronation and supination force following active VNS

Eligibility Criteria

Criteria

Ages Eligible for Study:

22 Years to 79 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Adult, aged 22-79
Ischemic stroke that occurred ≥ 12 months prior to enrollment
UEFM score of 20 to 50
Modified Rankin Score of 2, 3, or 4
Right vocal cord has normal movement when assessed by laryngoscopy
Women of reproductive potential must use contraceptive protection
Meets all clinical criteria for the surgical VNS implantation as determined by the PI, surgeon, and anesthesiologist

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

Deficits in language or attention that interfere with study participation
Severe spasticity (Modified Ashworth ≥ 3)
Medical or mental instability that would likely interfere with study protocol
Receiving any therapy (medication or otherwise) that would interfere with VNS, such as drugs that perturb neurotransmitter action (anticholinergics, adrenergic blockers, etc.)
Presence of any other implanted electrical stimulation device
Prior injury to vagus nerve
Lactating, pregnant, or plan to become pregnant
Participation in another interventional clinical trial
Clinical complications that hinder or contraindicate the surgical procedure
Abusive use of alcohol and/or illegal substances use
Active neoplastic disease.
Any medical condition or other circumstances that might interfere with their ability to return for follow-up visits in the judgment of the Investigator.
Any condition which, in the judgment of the Investigator, would preclude adequate evaluation of device's safety and performance.
Recent history of syncope
Recent history of dysphagia
Current or anticipated requirement for diathermy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Baylor Scott & White Institute for Rehabilitation	Dallas	Texas	United States	75246

Sponsors and Collaborators

Baylor Research Institute
The University of Texas at Dallas
University of Texas Southwestern Medical Center
National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Principal Investigator: Michael Kilgard, PhD, University of Texas at Dallas
Principal Investigator: Robert Rennaker, PhD, University of Texas at Dallas
Study Director: Seth Hays, PhD, University of Texas at Dallas
Principal Investigator: Jane Wigginton, MD, University of Texas Southwestern Medical Center
Principal Investigator: Rita Hamilton, DO, Baylor Scott & White Institute for Rehabilitation
Study Director: Michael Foreman, MD, FACS, Baylor Health Care System
Study Director: Richard Naftalis, MD, FAANS, FACS, Baylor Health Care System
Study Director: Mark Powers, PhD, Baylor Health Care System
Study Director: Ann Marie Warren, PhD, Baylor Health Care System