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Spinal Cord InjuriesNCT04288245

Targeted Plasticity Therapy for Upper Limb Rehabilitation in Spinal Cord Injuries

A study testing Active Vagus Nerve Stimulation in people with Spinal Cord Injuries and Upper Extremity Paresis, run by Baylor Research Institute at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
Spinal Cord Injuries, Upper Extremity Paresis
What is being tested?
Active Vagus Nerve Stimulation
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
1 siteUnited States
Study dates
15 Feb 2021to Sep 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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

Who cannot join

  • 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
Show all 27Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Baylor University Medical Center

    Dallas, Texas, 75246

Other trials in United States

About this study

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.

Being tested
Active Vagus Nerve Stimulation, Placebo Vagus Nerve Stimulation
Keywords
Vagus Nerve Stimulation (VNS), Rehabilitation, Targeted Plasticity Therapy
Medical subject headings
Spinal Cord Injuries, Paresis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Active Vagus Nerve StimulationDevice

    Also called VNS, vagus nerve stimulation, paired VNS

    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.

  • Placebo Vagus Nerve StimulationDevice

    Also called placebo, control

    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.

Study groups in NCT04288245
Study groupRoleWhat they receive
Immediate Start Vagus Nerve Stimulation groupExperimentalThe 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.
Receives: Device: Active Vagus Nerve Stimulation
Delayed Start Vagus Nerve Stimulation groupPlacebo comparatorThe 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.
Receives: Device: Placebo Vagus Nerve Stimulation
Follow-On Study GroupExperimentalThe 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.
Receives: Device: Active Vagus Nerve Stimulation

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (4)

  1. Restore System Feasibility during Rehabilitation

    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.

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

  2. Quantitative Force and Range of Motion Assessment

    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.

    Measured: Week 1, 6, 13, 20

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

    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.

    Measured: Week 1, 6, 13, 20

  4. Jebsen-Taylor Hand Function Test

    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

    Measured: Week 1, 6, 13, 20

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Feb 2020
  2. Study start15 Feb 2021
  3. Primary completionSep 2026 (estimated)
  4. Study completionSep 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Device feasibility
Allocation
Randomised
Intervention model
Crossover
Model description
Double blind, randomized placebo controlled, optional open-label extension design
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04288245
Sponsor's protocol ID
019-356
Other IDs
N66001-17-2-4011
Status last verified
Jan 2026
First submitted
13 Nov 2019
Last updated
4 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 24891012

  • 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.

    PubMed 16909143

  • 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.

    PubMed 15609737

  • 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.

    PubMed 21228773

  • 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.

    PubMed 24309259

  • 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.

    PubMed 17852230

  • 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.

    PubMed 5788487

  • 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.

    PubMed 21568688

  • 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.

    PubMed 22330108

  • 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.

    PubMed 11556941

  • 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.

    PubMed 24469147

  • 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.

    PubMed 6880820

  • 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.

    PubMed 40399668

Questions about this trial

What is this clinical trial studying?

A study testing Active Vagus Nerve Stimulation in people with Spinal Cord Injuries and Upper Extremity Paresis, run by Baylor Research Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Events [Device Safety] (time frame: Week 1, 4, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04288245, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2026.

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