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Targeted Plasticity Therapy for Upper Limb Rehabilitation in Spinal Cord Injuries

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04288245
Recruitment Status : Not yet recruiting
First Posted : February 28, 2020
Last Update Posted : December 31, 2020
Sponsor:
Collaborators:
Wings for Life - spinal cord research foundation
Defense Advanced Research Projects Agency
The University of Texas at Dallas
University of Texas Southwestern Medical Center
Information provided by (Responsible Party):
Baylor Research Institute

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.

Condition or disease Intervention/treatment Phase
Spinal Cord Injuries Upper Extremity Paresis Device: Active Vagus Nerve Stimulation Device: Placebo Vagus Nerve Stimulation Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Double blind, randomized placebo controlled, optional open-label extension design
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Device Feasibility
Official Title: Targeted Plasticity Therapy for Upper Limb Rehabilitation in Spinal Cord Injuries
Estimated Study Start Date : January 2021
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2026

Resource links provided by the National Library of Medicine


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 6 weeks during phase 1. For phase 2, all subjects will be provided 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 6 weeks. Participants that elect to continue in the open-label extension will be assessed approximately 1 week after the conclusion of the additional 18 sessions of therapy.
Device: Active Vagus Nerve Stimulation
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.
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 6 weeks during phase 1. For phase 2, all subjects will be provided 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 6 weeks. Participants that elect to continue in the open-label extension will be assessed approximately 1 week after the conclusion of the additional 18 sessions of therapy.
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




Primary Outcome Measures :
  1. Incidence of Adverse Events [Device Safety] [ Time Frame: From Week 1 through study follow-up, approximately two years from the date of implant ]
    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 :
  1. Restore System Feasibility during Rehabilitation [ Time Frame: Weeks 7-12, Weeks 14-19 ]
    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.

  2. Quantitative Force and Range of Motion Assessment [ Time Frame: 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.

  3. Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • Participants with prior right-sided anterior cervical surgery will require laryngoscopy prior to randomization. Those with evidence of recurrent laryngeal nerve injury will be excluded.
  • Participants with prior left sided anterior cervical surgery will be eligible, regardless of prior recurrent laryngeal nerve injury. However, if at surgery there is too much scar tissue for safe implantation the surgery will be abandoned to ensure participant safety
  • 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
  • Participants with 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.).
  • Participants with active neoplastic disease.
  • Participants with significant local circulatory problems, (e.g. thrombophlebitis and lymphedema, and clinically-significant hypotension or bradycardia).
  • 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.
  • Any condition which, in the judgment of the Investigator, would preclude adequate evaluation of device's safety and performance.
  • Aphasia and other cognitive deficits may be present but participants will be excluded if are unable to understand the potential risks and benefits of the study or 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04288245


Contacts
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Contact: Victoria Warren, RN 214-563-9001 victoria.warren@utdallas.edu
Contact: Emma Turner, BA 214-865-2416 emma.turner@bswhealth.org

Sponsors and Collaborators
Baylor Research Institute
Wings for Life - spinal cord research foundation
Defense Advanced Research Projects Agency
The University of Texas at Dallas
University of Texas Southwestern Medical Center
Investigators
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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: Mark Powers, PhD Baylor Health Care System
Study Director: Richard Naftalis, MD, FAANS, FACS Baylor Health Care System
Publications:

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Responsible Party: Baylor Research Institute
ClinicalTrials.gov Identifier: NCT04288245    
Other Study ID Numbers: 019-356
N66001-17-2-4011 ( Other Grant/Funding Number: Naval Information Warfare Center, Pacific )
First Posted: February 28, 2020    Key Record Dates
Last Update Posted: December 31, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Baylor Research Institute:
Vagus Nerve Stimulation (VNS)
Rehabilitation
Targeted Plasticity Therapy
Additional relevant MeSH terms:
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Spinal Cord Injuries
Paresis
Wounds and Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Neurologic Manifestations