Harnessing Neuroplasticity of Postural Sensorimotor Networks Using Non-Invasive Spinal Neuromodulation to Maximize Functional Recovery After Spinal Cord Injury

NCT06213012 | Recruiting DMC FDA Device

• 2 other identifiers: PRO000374835R01NS119587-02
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

It has been demonstrated that the human lumbosacral spinal cord can be neuromodulated with epidural (ESS) and transcutaneous (TSS) spinal cord stimulation to enable recovery of standing and volitional control of the lower limbs after complete motor paralysis due to spinal cord injury (SCI). The work proposed herein will examine and identify distinct electrophysiological mechanisms underlying transcutaneous spinal stimulation (TSS) and epidural spinal stimulation (ESS) to define how these approaches determine the ability to maintain self-assisted standing after SCI.

Conditions

Spinal Cord Injuries; Neuromodulation

Outcome Measures

Primary Outcomes (1)

• Assessment of force generation by lower limbs

  Neuromotor outcomes will be assessed during supine and upright standing, focusing on leg extension force output. Measurements will be taken under various conditions, including voluntary effort without spinal stimulation, and in the presence of Transcutaneous Spinal Stimulation (TSS), Epidural Spinal Stimulation (ESS), or Sham stimulation. The force output will be quantified in newtons (N). The magnitude of EMG signals will be quantified and expressed in millivolts (mV).

  Baseline 1(week 1), baseline 2(week 6), post interventions (week 11), and follow up (week 16)

Secondary Outcomes (2)

• Assessment of neurological status

  Baseline 1(week 1), baseline 2(week 6), post interventions (week 11), and follow up (week 16)

• Assessment of Independence

  Baseline 1(week 1), baseline 2(week 6), post interventions (week 11), and follow up (week 16)

Study Arms (3)

Transcutaneous Spinal Stimulation (TSS)

ACTIVE COMPARATOR

Spinal Stimulation delivered over the skin using a research stimulator with conventional surface electrodes during research visits.

Device: Transcutaneous Spinal cord Stimulation

Sham

SHAM COMPARATOR

Sham Stimulation delivered over the skin using a research stimulator with conventional surface electrodes during research visits. Sham stimulation will be delivered using the intensity of stimulation set as during active sessions of ESS, but then gradually decreased down to zero in approximately 30 s. There will be 5-10 minute breaks interspersed between intervals of stimulation, and will vary according to the individual's tolerance and fatigue levels

Device: Transcutaneous Spinal cord Stimulation

Epidural Spinal Stimulation (ESS)

EXPERIMENTAL

Stimulation delivered internally using an implanted device operated by an external control (only used during research visits).

Device: Epidural Spinal Stimulation (ESS)

Interventions

Transcutaneous Spinal cord Stimulation DEVICE

Delivered using a constant-current stimulator

Sham; Transcutaneous Spinal Stimulation (TSS)

Epidural Spinal Stimulation (ESS) DEVICE

The device used for ESS, the CoverEdgeX 32 Surgical Lead system (Boston Scientific, USA), is a device approved by the FDA used in the treatment of severe pain and is approved for individuals to manage chronic pain when other treatments have not been effective. If you are in the ESS group, you will have surgery to have the stimulator placed and the stimulator will be removed at an office visit towards the end of the study.

Epidural Spinal Stimulation (ESS)

Eligibility Criteria

• Age: 22 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants must be able to provide a provision of a signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, aged 22-75 years old.
• Documentation from the participant's primary treating physician confirming a stable medical condition.
• Inability to maintain standing independently without external support due to SCI AIS A-C.
• Ability to tolerate at least 15 minutes in an upright (supported) position.
• Able to self-transfer from the wheelchair and demonstrate active range of motion of bilateral upper extremities in gravity dependent plane.
• Able to passively range bilateral lower extremities within normal mobility parameters including:
• greater than 90 degrees of hip flexion and 165 degrees of hip extension;
• greater than 90 degrees of knee flexion and reach neutral knee extension of 180 degrees;
• neutral ankle position reaching a minimum of 90 degrees of dorsiflexion.
• Participants should be on a stable intrathecal baclofen or oral anti-spasticity regimen/dose for the period of the study unless advised otherwise by their physician.
• to 30 years post spinal cord injury.
• Non-progressive spinal cord injury.
• Neurological level of injury below C4 and above T12 (excluding conus injury and/or indications of lower motor neuron injury).

You may not qualify if:

• Ability to maintain standing independently without external support.
• Currently involved in another rehabilitation training of the lower extremities.
• Active pressure sores, unhealed bone fractures, peripheral neuropathies, or painful musculoskeletal dysfunction (including but not limited to contractures in the upper and lower extremities).
• Any ongoing medical condition which would preclude participant from regular physical activity (including but not limited to: cardiopulmonary disease, uncontrollable autonomic dysreflexia or orthostatic hypotension, active urinary tract infections, pregnant or nursing).
• Intrathecal baclofen pump therapy for spasticity not compatible with 3T MRI.
• Must not have received Botox injections to primary lower extremity and trunk musculature within the past 3 months, resulting in absence of muscle tone and precluding response to electrical stimulation therapy.
• Current or history of neuromuscular conditions (including but not limited to: unhealed ligament of muscular tears in the upper or lower extremities, pain in weight bearing positions for upper and lower extremities).
• Clinically significant depression, psychiatric disorders, or ongoing drug abuse, including heavy alcohol use.
• Any reason the PI or treating physician may deem as harmful to the participant to enroll or continue in the study.
• Body Mass Index (BMI) over 30.
• Pregnancy.
• Use a ventilator or diaphragmatic pacer.
• Participants with the following conditions will be excluded from TMS, but may take part in the overall study:
• Personal or first-degree family history of seizures or epilepsy.
• Metal in the head, except mouth implants.

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

Related Publications (17)

• Biering-Sorensen F, Hansen B, Lee BS. Non-pharmacological treatment and prevention of bone loss after spinal cord injury: a systematic review. Spinal Cord. 2009 Jul;47(7):508-18. doi: 10.1038/sc.2008.177. Epub 2009 Jan 27.

  PMID: 19172152 BACKGROUND

• Harkema SJ, Ferreira CK, van den Brand RJ, Krassioukov AV. Improvements in orthostatic instability with stand locomotor training in individuals with spinal cord injury. J Neurotrauma. 2008 Dec;25(12):1467-75. doi: 10.1089/neu.2008.0572.

  PMID: 19118454 RESULT

• Agarwal S, Triolo RJ, Kobetic R, Miller M, Bieri C, Kukke S, Rohde L, Davis JA Jr. Long-term user perceptions of an implanted neuroprosthesis for exercise, standing, and transfers after spinal cord injury. J Rehabil Res Dev. 2003 May-Jun;40(3):241-52.

  PMID: 14582528 RESULT

• Walter JS, Sola PG, Sacks J, Lucero Y, Langbein E, Weaver F. Indications for a home standing program for individuals with spinal cord injury. J Spinal Cord Med. 1999 Fall;22(3):152-8. doi: 10.1080/10790268.1999.11719564.

  PMID: 10685379 RESULT

• Fernhall B, Heffernan K, Jae SY, Hedrick B. Health implications of physical activity in individuals with spinal cord injury: a literature review. J Health Hum Serv Adm. 2008 Spring;30(4):468-502.

  PMID: 18236700 RESULT

• Anneken V, Hanssen-Doose A, Hirschfeld S, Scheuer T, Thietje R. Influence of physical exercise on quality of life in individuals with spinal cord injury. Spinal Cord. 2010 May;48(5):393-9. doi: 10.1038/sc.2009.137. Epub 2009 Oct 20.

  PMID: 19841634 RESULT

• Snoek GJ, IJzerman MJ, Hermens HJ, Maxwell D, Biering-Sorensen F. Survey of the needs of patients with spinal cord injury: impact and priority for improvement in hand function in tetraplegics. Spinal Cord. 2004 Sep;42(9):526-32. doi: 10.1038/sj.sc.3101638.

  PMID: 15224087 RESULT

• Sayenko DG,Rath M,Ferguson AR,Burdick JW,Havton LA,Edgerton VR,Gerasimenko YP

  RESULT

• Gill ML, Grahn PJ, Calvert JS, Linde MB, Lavrov IA, Strommen JA, Beck LA, Sayenko DG, Van Straaten MG, Drubach DI, Veith DD, Thoreson AR, Lopez C, Gerasimenko YP, Edgerton VR, Lee KH, Zhao KD. Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nat Med. 2018 Nov;24(11):1677-1682. doi: 10.1038/s41591-018-0175-7. Epub 2018 Sep 24.

  PMID: 30250140 RESULT

• Grahn PJ, Lavrov IA, Sayenko DG, Van Straaten MG, Gill ML, Strommen JA, Calvert JS, Drubach DI, Beck LA, Linde MB, Thoreson AR, Lopez C, Mendez AA, Gad PN, Gerasimenko YP, Edgerton VR, Zhao KD, Lee KH. Enabling Task-Specific Volitional Motor Functions via Spinal Cord Neuromodulation in a Human With Paraplegia. Mayo Clin Proc. 2017 Apr;92(4):544-554. doi: 10.1016/j.mayocp.2017.02.014.

  PMID: 28385196 RESULT

• Angeli CA, Boakye M, Morton RA, Vogt J, Benton K, Chen Y, Ferreira CK, Harkema SJ. Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury. N Engl J Med. 2018 Sep 27;379(13):1244-1250. doi: 10.1056/NEJMoa1803588. Epub 2018 Sep 24.

  PMID: 30247091 RESULT

• Angeli CA,Edgerton VR,Gerasimenko YP,Harkema SJ

  RESULT

• Munoz Perez M, Cortes Velasco M, Martinez Elizondo G, Guitron Cantu A, Contreras Soto J, Forsbach Sanchez G. [Ovulation induction in normoprolactinemic anovulatory patients with bromocriptine and clomiphene citrate]. Ginecol Obstet Mex. 1988 Sep;56:256-62. No abstract available. Spanish.

  PMID: 3154251 RESULT

• Rossignol S, Frigon A. Recovery of locomotion after spinal cord injury: some facts and mechanisms. Annu Rev Neurosci. 2011;34:413-40. doi: 10.1146/annurev-neuro-061010-113746.

  PMID: 21469957 RESULT

• Campbell WW, Sahni SK, Pridgeon RM, Riaz G, Leshner RT. Intraoperative electroneurography: management of ulnar neuropathy at the elbow. Muscle Nerve. 1988 Jan;11(1):75-81. doi: 10.1002/mus.880110112.

  PMID: 2828944 RESULT

• Naslund TC, Merrell WJ, Nadeau JH, Wood AJ. Alpha-adrenergic blockade makes minimal contribution to ketanserin's hypotensive effect. Clin Pharmacol Ther. 1988 Dec;44(6):699-703. doi: 10.1038/clpt.1988.214.

  PMID: 2904312 RESULT

• Edgerton VR,Courtine G,Gerasimenko YP,Lavrov I,Ichiyama RM,Fong AJ,Cai LL,Otoshi CK,Tillakaratne NJ,Burdick JW,Roy RR

  RESULT

MeSH Terms

Conditions

Spinal Cord Injuries

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Dimitry Sayenko, MD, PhD

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jenny Dinh, BS

CONTACT

585-507-1706; jtdinh@houstonmethodist.org

Amanda Howes-Keith, MS

CONTACT

585-507-1706; achowes-keith@houstonmethodist.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientist, Associate Professor of Neurosurgery

Model Details: optional crossover arm for returning participants.

Study Record Dates

• First Submitted: October 26, 2023
• First Posted: January 19, 2024
• Study Start: December 6, 2023
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)