Clinical trial NCT04288245: Targeted Plasticity Therapy for Upper Limb Rehabilitation in Spinal Cord Injuries
Official title: Targeted Plasticity Therapy for Upper Limb Rehabilitation in Spinal Cord Injuries
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Spinal Cord Injuries
Upper Extremity Paresis
Keywords: Vagus Nerve Stimulation (VNS)
Rehabilitation
Targeted Plasticity Therapy
Lead sponsor: Baylor Research Institute
Sponsor class: OTHER
Collaborators: name: Wings for Life
name: Defense Advanced Research Projects Agency
name: The University of Texas at Dallas
name: University of Texas Southwestern Medical Center
First posted: 2020-02-28
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double blind, randomized placebo controlled, optional open-label extension design
Primary purpose: DEVICE_FEASIBILITY

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.


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 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

Primary outcomes:
measure: Incidence of Adverse Events [Device Safety]
timeFrame: From Week 1 through study follow-up, approximately two years from the date of implant
Secondary outcomes:
measure: Restore System Feasibility during Rehabilitation
timeFrame: Weeks 7-12, Weeks 14-19
measure: Quantitative Force and Range of Motion Assessment
timeFrame: Week 1, 6, 13, 20
measure: Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP)
timeFrame: Week 1, 6, 13, 20
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
Study officials:
affiliation: University of Texas at Dallas
name: Michael Kilgard, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas at Dallas
name: Robert Rennaker, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas at Dallas
name: Seth Hays, PhD
role: STUDY_DIRECTOR
affiliation: University of Texas Southwestern Medical Center
name: Jane Wigginton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor Scott & White Institute for Rehabilitation
name: Rita Hamilton, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor Health Care System
name: Michael Foreman, MD FACS
role: STUDY_DIRECTOR
affiliation: Baylor Health Care System
name: Mark Powers, PhD
role: STUDY_DIRECTOR
affiliation: Baylor Health Care System
name: Richard Naftalis, MD, FAANS, FACS
role: STUDY_DIRECTOR
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