- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04288245
Targeted Plasticity Therapy for Upper Limb Rehabilitation in Spinal Cord Injuries
September 12, 2023 updated by: Baylor Research Institute
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Estimated)
20
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Alvaro Carrera
- Phone Number: 469-831-5321
- Email: alvaro.carrera@bswhealth.org
Study Locations
-
-
Texas
-
Dallas, Texas, United States, 75246
- Recruiting
- Baylor University Medical Center
-
Contact:
- Alvaro Carrera
- Phone Number: 469-831-5321
- Email: alvaro.carrera@bswhealth.org
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 64 years (Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Device Feasibility
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / 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.
|
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:
|
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.
|
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:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
From Week 1 through study follow-up, approximately two years from the date of implant
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Weeks 7-12, Weeks 14-19
|
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.
|
Week 1, 6, 13, 20
|
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.
|
Week 1, 6, 13, 20
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- 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
- Study Director: Mark Powers, PhD, Baylor Health Care System
- Study Director: Richard Naftalis, MD, FAANS, FACS, Baylor Health Care System
- Principal Investigator: Rita Hamilton, DO, Baylor Scott & White Institute for Rehabilitation
- Study Director: Michael Foreman, MD FACS, Baylor Health Care System
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 15, 2021
Primary Completion (Estimated)
November 1, 2023
Study Completion (Estimated)
April 1, 2025
Study Registration Dates
First Submitted
November 13, 2019
First Submitted That Met QC Criteria
February 26, 2020
First Posted (Actual)
February 28, 2020
Study Record Updates
Last Update Posted (Actual)
September 13, 2023
Last Update Submitted That Met QC Criteria
September 12, 2023
Last Verified
January 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 019-356
- N66001-17-2-4011 (Other Grant/Funding Number: Naval Information Warfare Center, Pacific)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
Yes
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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