Spinal Cord Injuries, Upper Extremity Paresis
Conditions
Keywords
Vagus Nerve Stimulation (VNS), Rehabilitation, Targeted Plasticity Therapy
Brief summary
Texas Biomedical Device Center at UT Dallas 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. Recovery is associated with neural plasticity in spared motor networks in the brain and spinal cord. Moreover, an early feasibility study and an independent, double-blind, placebo-controlled study in chronic stroke participants indicate that VNS is safe in participants with upper limb deficits, and yields a clinically-significant three-fold increase in neural connections during rehabilitation exercises. Given the track record of safety and potential for VNS to enhance recovery of upper limb motor function in spinal cord injured individuals, the purpose of this double blind randomized placebo controlled optional open-label extension study is to assess the safety of using a new device to deliver vagus nerve stimulation to reduce symptom severity in participants with SCI. Additionally, the study will assess the prospective benefit of the system and garner an initial estimate of efficacy for a subsequent trial. Participants may undergo additional sessions of training with VNS.
Interventions
Stimulation of the vagus nerve that is paired with upper extremity rehabilitation. VNS stimulation as described in the current study consists of 0.5 s trains of 0.8 mA 100 µs biphasic pulses delivered at 30 Hz. Stimulation trains are delivered only during rehabilitation.
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.
Sponsors
Baylor Research Institute
Defense Advanced Research Projects Agency
The University of Texas at Dallas
University of Texas Southwestern Medical Center
Wings for Life
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DEVICE_FEASIBILITY
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Double blind, randomized placebo controlled, optional open-label extension design
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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 18-64 * In good general health as evidenced by medical history and diagnosed with first time cervical spinal cord injury resulting in an ASIA grade B, C, or D, and level 1 or better motor function as described by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). * SCI caused by trauma that occurred ≥ 12 months prior to enrollment * Meets all clinical criteria for the surgical VNS implantation as determined by the PI, surgeon, and anesthesiologist * Must demonstrate some residual upper limb and hand movement in either arm * Appropriate candidate for VNS implantation * Willing and able to comply with the study protocol
Exclusion criteria
An individual who meets any of the following criteria will be excluded from participation in this study: * Spinal cord injuries by sharp objects, firearms, and non-traumatic or congenital causes, even if at different levels of the spinal cord * Any evidence of recurrent laryngeal nerve injury (Evident during required laryngoscopy for all participants with Prior right-sided anterior cervical surgery- done prior to randomization) * Excessive scar tissue marking implantation unsafe (evident at surgery) * Concomitant clinically significant brain injuries * Prior injury to vagus nerve * Prior or current treatment with vagus nerve stimulation * Participant receiving any therapy (medication or otherwise) that would interfere with VNS * Pregnancy or lactation * Clinical complications that hinder or contraindicate the surgical procedure * Psychiatric disorders, psychosocial, and/or cognitive impairment that would interfere with study participation, as assessed by medical evaluation * Abusive use of alcohol and/or illegal substances use * Participation in other interventional clinical trial * Participants with known immunodeficiency including participants who are receiving or have received chronic corticosteroids, immunosuppressants, immunostimulating agents or radiation therapy within 6 months * Significant comorbidities or conditions associated with high risk for surgical or anesthetic survival (e.g. renal failure, peripheral vascular disease, unstable cardiac disease, poorly controlled diabetes, immunosuppression, etc.). * Active neoplastic disease. * Participants with significant local circulatory problems, (e.g. thrombophlebitis and lymphedema). * Participants with any medical condition or other circumstances that might interfere with their ability to return for follow-up visits in the judgment of the Investigator, including systemic illness, neuromuscular, neurosensory, or musculoskeletal deficiency that would render the participant unable to perform appropriate postoperative rehabilitation. * Any condition which, in the judgment of the Investigator, would preclude adequate evaluation of device's safety and performance. * Aphasia and other cognitive deficits that make understanding the potential risks and benefits of the study impossible for participant. Inability to personally provide informed consent. * A recent history of syncope * A recent history of dysphagia * Currently require, or are likely to require diathermy * Significant respiratory issues that would interfere with participation * Non-English speaking * Patients who are acutely suicidal and/or have been admitted for a suicide attempt * Incarceration or legal detention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events [Device Safety] | Week 1, 4, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 | 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
| Measure | Time frame | Description |
|---|---|---|
| Restore System Feasibility during Rehabilitation | Weeks 7, 8, 9, 10, 11, 12, 14, 15, 16, 17, 18, 19 | If stimulation delivery is successful during the active portion of therapy sessions then the system is feasible to use. The primary endpoint will be: greater than 50% of the valid attempts to stimulate are successful per the ReStore system log. |
| Quantitative Force and Range of Motion Assessment | Week 1, 6, 13, 20 | This is a physical assessment of upper limb changes in force/torque as a result of VNS paired rehabilitation. The primary 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, and 10% increase in wrist pronation and supination force following active VNS. This will serve as an efficacy measurement to use as basis for estimate of sample size for a pivotal trial. |
| Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) | Week 1, 6, 13, 20 | Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) is a measure used for spinal cord injury patients. The measure includes five subsets of questions designed to quantitatively measure clinical upper limb impairment (Kalsi-Ryan et al., 2012). The primary endpoint will be: \>4 point shift in GRASSP assessment following active VNS. This will serve as an efficacy measurement to use as basis for estimate of sample size for a pivotal trial. |
| Jebsen-Taylor Hand Function Test | Week 1, 6, 13, 20 | Seven-item test of hand functions commonly used in activities of daily living (Jebsen et al, 1969). The items tested include range of fine motor, weighted and non-weighted hand function activities. The primary endpoint will be: 10% improvement in time to complete JTHF test following VNS therapy |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichael Kilgard, PhD
The University of Texas at Dallas
PRINCIPAL_INVESTIGATORRobert Rennaker, PhD
The University of Texas at Dallas
STUDY_DIRECTORSeth Hays, PhD
The University of Texas at Dallas
PRINCIPAL_INVESTIGATORJane Wigginton, MD
University of Texas Southwestern Medical Center
PRINCIPAL_INVESTIGATORRita Hamilton, DO
Baylor Scott & White Institute for Rehabilitation
STUDY_DIRECTORMichael Foreman, MD FACS
Baylor Health Care System
STUDY_DIRECTORMark Powers, PhD
Baylor Health Care System
STUDY_DIRECTORRichard Naftalis, MD, FAANS, FACS
Baylor Health Care System
Outcome results
None listed