Targeted Plasticity Therapy for Upper Limb Rehabilitation in Spinal Cord Injuries

NCT04288245 | Active Not Recruiting DMC FDA Device

• 2 other identifiers: 019-356N66001-17-2-4011
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Spinal Cord Injuries; Upper Extremity Paresis

Keywords

Vagus Nerve Stimulation (VNS); Rehabilitation; Targeted Plasticity Therapy

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events [Device Safety]

  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.

  Week 1, 4, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Secondary Outcomes (4)

• Restore System Feasibility during Rehabilitation

  Weeks 7, 8, 9, 10, 11, 12, 14, 15, 16, 17, 18, 19

• Quantitative Force and Range of Motion Assessment

  Week 1, 6, 13, 20

• Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP)

  Week 1, 6, 13, 20

• Jebsen-Taylor Hand Function Test

  Week 1, 6, 13, 20

Study Arms (3)

Immediate Start Vagus Nerve Stimulation group

EXPERIMENTAL

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

Delayed Start Vagus Nerve Stimulation group

PLACEBO COMPARATOR

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

Follow-On Study Group

EXPERIMENTAL

The Follow-On Study group will receive up to 112 rehabilitative sessions with active VNS over the course of approximately 36 weeks after completion of Phase II. Participants will be provided with a system of rehabilitative devices to utilize at home.

Device: Active Vagus Nerve Stimulation

Interventions

Active Vagus Nerve Stimulation DEVICE

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.

Also known as: VNS, vagus nerve stimulation, paired VNS

Follow-On Study Group; Immediate Start Vagus Nerve Stimulation group

Placebo Vagus Nerve Stimulation DEVICE

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.

Also known as: placebo, control

Delayed Start Vagus Nerve Stimulation group

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.).

Sponsors & Collaborators

• Baylor Research Institute: lead
• Defense Advanced Research Projects Agency: collaborator
• The University of Texas at Dallas: collaborator
• University of Texas Southwestern Medical Center: collaborator
• Wings for Life: collaborator

Study Sites (1)

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Related Publications (13)

• Biering-Sorensen F, Bryden A, Curt A, Friden J, Harvey LA, Mulcahey MJ, Popovic MR, Prochazka A, Sinnott KA, Snoek G. International spinal cord injury upper extremity basic data set. Spinal Cord. 2014 Sep;52(9):652-7. doi: 10.1038/sc.2014.87. Epub 2014 Jun 3.

  PMID: 24891012 BACKGROUND

• Catz A, Itzkovich M, Tesio L, Biering-Sorensen F, Weeks C, Laramee MT, Craven BC, Tonack M, Hitzig SL, Glaser E, Zeilig G, Aito S, Scivoletto G, Mecci M, Chadwick RJ, El Masry WS, Osman A, Glass CA, Silva P, Soni BM, Gardner BP, Savic G, Bergstrom EM, Bluvshtein V, Ronen J. A multicenter international study on the Spinal Cord Independence Measure, version III: Rasch psychometric validation. Spinal Cord. 2007 Apr;45(4):275-91. doi: 10.1038/sj.sc.3101960. Epub 2006 Aug 15.

  PMID: 16909143 BACKGROUND

• Corson K, Gerrity MS, Dobscha SK. Screening for depression and suicidality in a VA primary care setting: 2 items are better than 1 item. Am J Manag Care. 2004 Nov;10(11 Pt 2):839-45.

  PMID: 15609737 BACKGROUND

• Engineer ND, Riley JR, Seale JD, Vrana WA, Shetake JA, Sudanagunta SP, Borland MS, Kilgard MP. Reversing pathological neural activity using targeted plasticity. Nature. 2011 Feb 3;470(7332):101-4. doi: 10.1038/nature09656. Epub 2011 Jan 12.

  PMID: 21228773 BACKGROUND

• Hays SA, Rennaker RL, Kilgard MP. Targeting plasticity with vagus nerve stimulation to treat neurological disease. Prog Brain Res. 2013;207:275-99. doi: 10.1016/B978-0-444-63327-9.00010-2.

  PMID: 24309259 BACKGROUND

• Itzkovich M, Gelernter I, Biering-Sorensen F, Weeks C, Laramee MT, Craven BC, Tonack M, Hitzig SL, Glaser E, Zeilig G, Aito S, Scivoletto G, Mecci M, Chadwick RJ, El Masry WS, Osman A, Glass CA, Silva P, Soni BM, Gardner BP, Savic G, Bergstrom EM, Bluvshtein V, Ronen J, Catz A. The Spinal Cord Independence Measure (SCIM) version III: reliability and validity in a multi-center international study. Disabil Rehabil. 2007 Dec 30;29(24):1926-33. doi: 10.1080/09638280601046302. Epub 2007 Mar 5.

  PMID: 17852230 BACKGROUND

• Jebsen RH, Taylor N, Trieschmann RB, Trotter MJ, Howard LA. An objective and standardized test of hand function. Arch Phys Med Rehabil. 1969 Jun;50(6):311-9. No abstract available.

  PMID: 5788487 BACKGROUND

• Kalsi-Ryan S, Beaton D, Curt A, Duff S, Popovic MR, Rudhe C, Fehlings MG, Verrier MC. The Graded Redefined Assessment of Strength Sensibility and Prehension: reliability and validity. J Neurotrauma. 2012 Mar 20;29(5):905-14. doi: 10.1089/neu.2010.1504. Epub 2011 Aug 12.

  PMID: 21568688 BACKGROUND

• Kirshblum SC, Burns SP, Biering-Sorensen F, Donovan W, Graves DE, Jha A, Johansen M, Jones L, Krassioukov A, Mulcahey MJ, Schmidt-Read M, Waring W. International standards for neurological classification of spinal cord injury (revised 2011). J Spinal Cord Med. 2011 Nov;34(6):535-46. doi: 10.1179/204577211X13207446293695. No abstract available.

  PMID: 22330108 BACKGROUND

• Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x.

  PMID: 11556941 BACKGROUND

• Widerstrom-Noga E, Biering-Sorensen F, Bryce TN, Cardenas DD, Finnerup NB, Jensen MP, Richards JS, Siddall PJ. The International Spinal Cord Injury Pain Basic Data Set (version 2.0). Spinal Cord. 2014 Apr;52(4):282-6. doi: 10.1038/sc.2014.4. Epub 2014 Jan 28.

  PMID: 24469147 BACKGROUND

• Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x.

  PMID: 6880820 BACKGROUND

• Kilgard MP, Epperson JD, Adehunoluwa EA, Swank C, Porter AL, Pruitt DT, Gallaway HL, Stevens C, Gillespie J, Arnold D, Powers MB, Hamilton RG, Naftalis RC, Foreman ML, Wigginton JG, Hays SA, Rennaker RL. Closed-loop vagus nerve stimulation aids recovery from spinal cord injury. Nature. 2025 Jul;643(8073):1030-1036. doi: 10.1038/s41586-025-09028-5. Epub 2025 May 21.

  PMID: 40399668 DERIVED

MeSH Terms

Conditions

Spinal Cord Injuries; Paresis

Interventions

Vagus Nerve Stimulation

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics

Study Officials

• Michael Kilgard, PhD

  The University of Texas at Dallas

  PRINCIPAL INVESTIGATOR

• Robert Rennaker, PhD

  The University of Texas at Dallas

  PRINCIPAL INVESTIGATOR

• Seth Hays, PhD

  The University of Texas at Dallas

  STUDY DIRECTOR

• Jane Wigginton, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

• Rita Hamilton, DO

  Baylor Scott & White Institute for Rehabilitation

  PRINCIPAL INVESTIGATOR

• 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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: DEVICE FEASIBILITY
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double blind, randomized placebo controlled, optional open-label extension design

Study Record Dates

• First Submitted: November 13, 2019
• First Posted: February 28, 2020
• Study Start: February 15, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: March 4, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)