Wireless Nerve Stimulation Device To Enhance Recovery After Stroke

Overview

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.

Interventions

• 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.
• 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.

Primary outcome measures

• Incidence of Adverse Events [Device Safety] [Time frame: From Week 1 through study follow-up, approximately two years after the implant date or final session of rehabilitation (whichever comes second)]

Secondary outcome measures (6)

• ReStore Stimulation Successes [Time frame: Weeks 6-11, during follow-on intervention visits 2-13, 14-25, and 25-36]
• Upper-Extremity Fugl-Meyer Assessment (UEFM) [Time frame: Weeks 1, 3, 10, 17]
• Wolf Motor Task Functional Ability Scale [Time frame: Weeks 1, 3, 10, 17]
• Action Research Arm Test [Time frame: Weeks 1, 5, 12, 19, 20, 24, 32]
• Modified Rankin Scale [Time frame: Weeks 1, 5, 12, 19, 20, 24, 32]
• Quantitative Force and Range of Motion Assessment [Time frame: Weeks 1, 3, 10, 17]

Eligibility criteria

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 or hemorrhagic 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
• Participants with sickle cell, lupus, clotting disorders or active neoplastic disease.
• Participants with any 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
• Uncontrolled hypertension
• Diagnosed with Cerebral amyloid angiopathy

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Triple blind

Primary purpose

Device feasibility

Study locations

United States · 1 center

• Baylor Scott & White Institute for Rehabilitation — Dallas

Publications

• Engineer ND, Kimberley TJ, Prudente CN, Dawson J, Tarver WB, Hays SA. Targeted Vagus Nerve Stimulation for Rehabilitation After Stroke. Front Neurosci. 2019 Mar 29;13:280. doi: 10.3389/fnins.2019.00280. eCollection 2019. PMID 30983963
• Khodaparast N, Hays SA, Sloan AM, Hulsey DR, Ruiz A, Pantoja M, Rennaker RL 2nd, Kilgard MP. Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke. Neurobiol Dis. 2013 Dec;60:80-8. doi: 10.1016/j.nbd.2013.08.002. Epub 2013 Aug 15. PMID 23954448
• Khodaparast N, Hays SA, Sloan AM, Fayyaz T, Hulsey DR, Rennaker RL 2nd, Kilgard MP. Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke. Neurorehabil Neural Repair. 2014 Sep;28(7):698-706. doi: 10.1177/1545968314521006. Epub 2014 Feb 18. PMID 24553102
• Hays SA, Khodaparast N, Ruiz A, Sloan AM, Hulsey DR, Rennaker RL 2nd, Kilgard MP. The timing and amount of vagus nerve stimulation during rehabilitative training affect poststroke recovery of forelimb strength. Neuroreport. 2014 Jun 18;25(9):676-82. doi: 10.1097/WNR.0000000000000154. PMID 24818637
• Hays SA, Khodaparast N, Hulsey DR, Ruiz A, Sloan AM, Rennaker RL 2nd, Kilgard MP. Vagus nerve stimulation during rehabilitative training improves functional recovery after intracerebral hemorrhage. Stroke. 2014 Oct;45(10):3097-100. doi: 10.1161/STROKEAHA.114.006654. Epub 2014 Aug 21. PMID 25147331
• Hays SA, Ruiz A, Bethea T, Khodaparast N, Carmel JB, Rennaker RL 2nd, Kilgard MP. Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats. Neurobiol Aging. 2016 Jul;43:111-8. doi: 10.1016/j.neurobiolaging.2016.03.030. Epub 2016 Apr 7. PMID 27255820
• Khodaparast N, Kilgard MP, Casavant R, Ruiz A, Qureshi I, Ganzer PD, Rennaker RL 2nd, Hays SA. Vagus Nerve Stimulation During Rehabilitative Training Improves Forelimb Recovery After Chronic Ischemic Stroke in Rats. Neurorehabil Neural Repair. 2016 Aug;30(7):676-84. doi: 10.1177/1545968315616494. Epub 2015 Nov 4. PMID 26542082
• Pruitt DT, Schmid AN, Kim LJ, Abe CM, Trieu JL, Choua C, Hays SA, Kilgard MP, Rennaker RL. Vagus Nerve Stimulation Delivered with Motor Training Enhances Recovery of Function after Traumatic Brain Injury. J Neurotrauma. 2016 May 1;33(9):871-9. doi: 10.1089/neu.2015.3972. Epub 2015 Aug 5. PMID 26058501

Identifiers

NCT: NCT04534556 · 020-392 · UG3NS109497

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗