Restoring Hemodynamic Stability Using Targeted Epidural Spinal Stimulation Following Spinal Cord Injury

NCT05044923 | Unknown DMC

• 1 other identifier: REB21-0027
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to stimulate the circuits in the spinal cord that are directly responsible for hemodynamic control to restore hemodynamic stability in participants with chronic cervical or high-thoracic spinal cord injury. The ultimate objective of this study is to provide preliminary safety and efficacy measures on the ability of the hemodynamic Targeted Epidural Spinal Stimulation (TESS) to ensure the long-term management of hemodynamic instability and reduce the incidence and severity of orthostatic hypotension and autonomic dysreflexia episodes in individuals with chronic cervical or high-thoracic spinal cord injury. In addition, the long-term safety and efficacy of TESS on cardiovascular health, respiratory function, and quality of life in participants with chronic spinal cord injury will be evaluated.

Conditions

Spinal Cord Injuries

Keywords

orthostatic hypotension; autonomic dysreflexia; epidural stimulation; blood pressure

Outcome Measures

Primary Outcomes (1)

• Occurrence of Adverse Events and Serious Adverse Events that are deemed related or possibly related to the study procedure or to the study investigational system, from implant surgery until the end of study

  Investigate the preliminary safety of hemodynamic targeted epidural spinal stimulation (TESS) to modulate pressor responses and manage blood pressure instability in participants with chronic SCI located between C3 and T6 and who suffer from severe orthostatic hypotension.

  From implant surgery through study completion, an average of 7 months

Secondary Outcomes (10)

• Orthostatic head-up tilt test

  At baseline and during the testing phase, an average of 9 months

• Daily stimulation log

  From implant surgery through study completion, an average of 7 months

• Echocardiogram (Ejection Fraction)

  At baseline and during the testing phase, an average of 9 months

• Echocardiogram (Strain)

  At baseline and during the testing phase, an average of 9 months

• Vascular ultrasound

  At baseline and during the testing phase, an average of 9 months

Study Arms (1)

Targeted Epidural Spinal Stimulation

EXPERIMENTAL

Participants will undergo surgery to implant devices that will be used for Targeted Epidural Spinal Stimulation (TESS).

Device: Targeted Epidural Spinal Stimulation

Interventions

Targeted Epidural Spinal Stimulation DEVICE

Two lead electrodes (Specify Surescan 5-6-5 Leads, Model 977C190 Medtronic) will be implanted epidurally over the dorsal aspect of the spinal cord through two laminotomies. Two implantable pulse generators (Intellis™ with AdaptiveStim™, Model 97715 Medtronic) will be connected to the lead electrodes and implanted in the upper buttocks of the participant.

Targeted Epidural Spinal Stimulation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 70 years old
• Able to undergo the informed consent/assent process
• Radiologically confirmed spinal cord injury
• Spinal cord injury between C3 and T6
• Classified with American Spinal Injury Association Impairment Scale (AIS) A or B Spinal cord injury
• Stable medical, physical and psychological condition as considered by Investigators
• Greater than 1 year since initial injury and at least 6 months from any required spinal instrumentation
• Confirmed orthostatic hypotension and autonomic dysreflexia
• Willing to attend all scheduled appointments

You may not qualify if:

• Diseases and conditions that would increase the morbidity and mortality of spinal cord injury surgery
• The inability to withhold antiplatelet/anticoagulation agents perioperatively
• History of myocardial infarction or cerebrovascular event
• Other conditions that would make the subject unable to participate in testing in the judgment of the investigators
• Current and anticipated need for opioid pain medications or pain that would prevent full participation in the trial in the judgement of the investigators
• Current clinical diagnosis of mental illness
• Clinically significant cognitive impairment
• Current substance or alcohol abuse
• Botulinum toxin injections in the previous 6 months
• Presence of significant pressure ulcers
• Recurrent urinary tract infection refractory to antibiotics
• Current pregnancy
• Current breast feeding
• Unhealed spinal fractures
• Presence of indwelling baclofen or insulin pump

Sponsors & Collaborators

• Aaron Phillips: lead

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N 4N1, Canada

RECRUITING

Related Publications (13)

• Squair JW, Gautier M, Mahe L, Soriano JE, Rowald A, Bichat A, Cho N, Anderson MA, James ND, Gandar J, Incognito AV, Schiavone G, Sarafis ZK, Laskaratos A, Bartholdi K, Demesmaeker R, Komi S, Moerman C, Vaseghi B, Scott B, Rosentreter R, Kathe C, Ravier J, McCracken L, Kang X, Vachicouras N, Fallegger F, Jelescu I, Cheng Y, Li Q, Buschman R, Buse N, Denison T, Dukelow S, Charbonneau R, Rigby I, Boyd SK, Millar PJ, Moraud EM, Capogrosso M, Wagner FB, Barraud Q, Bezard E, Lacour SP, Bloch J, Courtine G, Phillips AA. Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury. Nature. 2021 Feb;590(7845):308-314. doi: 10.1038/s41586-020-03180-w. Epub 2021 Jan 27.

  PMID: 33505019 BACKGROUND

• Anderson KD. Targeting recovery: priorities of the spinal cord-injured population. J Neurotrauma. 2004 Oct;21(10):1371-83. doi: 10.1089/neu.2004.21.1371.

  PMID: 15672628 BACKGROUND

• Cragg JJ, Noonan VK, Krassioukov A, Borisoff J. Cardiovascular disease and spinal cord injury: results from a national population health survey. Neurology. 2013 Aug 20;81(8):723-8. doi: 10.1212/WNL.0b013e3182a1aa68. Epub 2013 Jul 24.

  PMID: 23884034 BACKGROUND

• Illman A, Stiller K, Williams M. The prevalence of orthostatic hypotension during physiotherapy treatment in patients with an acute spinal cord injury. Spinal Cord. 2000 Dec;38(12):741-7. doi: 10.1038/sj.sc.3101089.

  PMID: 11175374 BACKGROUND

• Phillips AA, Krassioukov AV. Contemporary Cardiovascular Concerns after Spinal Cord Injury: Mechanisms, Maladaptations, and Management. J Neurotrauma. 2015 Dec 15;32(24):1927-42. doi: 10.1089/neu.2015.3903. Epub 2015 Sep 1.

  PMID: 25962761 BACKGROUND

• Phillips AA, Krassioukov AV, Ainslie PN, Warburton DE. Perturbed and spontaneous regional cerebral blood flow responses to changes in blood pressure after high-level spinal cord injury: the effect of midodrine. J Appl Physiol (1985). 2014 Mar 15;116(6):645-53. doi: 10.1152/japplphysiol.01090.2013. Epub 2014 Jan 16.

  PMID: 24436297 BACKGROUND

• Phillips AA, Warburton DE, Ainslie PN, Krassioukov AV. Regional neurovascular coupling and cognitive performance in those with low blood pressure secondary to high-level spinal cord injury: improved by alpha-1 agonist midodrine hydrochloride. J Cereb Blood Flow Metab. 2014 May;34(5):794-801. doi: 10.1038/jcbfm.2014.3. Epub 2014 Jan 29.

  PMID: 24473484 BACKGROUND

• Phillips AA, Elliott SL, Zheng MM, Krassioukov AV. Selective alpha adrenergic antagonist reduces severity of transient hypertension during sexual stimulation after spinal cord injury. J Neurotrauma. 2015 Mar 15;32(6):392-6. doi: 10.1089/neu.2014.3590. Epub 2014 Dec 5.

  PMID: 25093677 BACKGROUND

• Krassioukov A, Eng JJ, Warburton DE, Teasell R; Spinal Cord Injury Rehabilitation Evidence Research Team. A systematic review of the management of orthostatic hypotension after spinal cord injury. Arch Phys Med Rehabil. 2009 May;90(5):876-85. doi: 10.1016/j.apmr.2009.01.009.

  PMID: 19406310 BACKGROUND

• Squair JW, Phillips AA, Harmon M, Krassioukov AV. Emergency management of autonomic dysreflexia with neurologic complications. CMAJ. 2016 Oct 18;188(15):1100-1103. doi: 10.1503/cmaj.151311. Epub 2016 May 24. No abstract available.

  PMID: 27221275 BACKGROUND

• Phillips AA, Krassioukov AV, Ainslie PN, Warburton DE. Baroreflex function after spinal cord injury. J Neurotrauma. 2012 Oct 10;29(15):2431-45. doi: 10.1089/neu.2012.2507. Epub 2012 Sep 20.

  PMID: 22897489 BACKGROUND

• Courtine G, Gerasimenko Y, van den Brand R, Yew A, Musienko P, Zhong H, Song B, Ao Y, Ichiyama RM, Lavrov I, Roy RR, Sofroniew MV, Edgerton VR. Transformation of nonfunctional spinal circuits into functional states after the loss of brain input. Nat Neurosci. 2009 Oct;12(10):1333-42. doi: 10.1038/nn.2401. Epub 2009 Sep 20.

  PMID: 19767747 BACKGROUND

• Wagner FB, Mignardot JB, Le Goff-Mignardot CG, Demesmaeker R, Komi S, Capogrosso M, Rowald A, Seanez I, Caban M, Pirondini E, Vat M, McCracken LA, Heimgartner R, Fodor I, Watrin A, Seguin P, Paoles E, Van Den Keybus K, Eberle G, Schurch B, Pralong E, Becce F, Prior J, Buse N, Buschman R, Neufeld E, Kuster N, Carda S, von Zitzewitz J, Delattre V, Denison T, Lambert H, Minassian K, Bloch J, Courtine G. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. 2018 Nov;563(7729):65-71. doi: 10.1038/s41586-018-0649-2. Epub 2018 Oct 31.

  PMID: 30382197 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries; Hypotension, Orthostatic; Autonomic Dysreflexia

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Aaron Phillips, PhD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

4032107438; restorenetwork@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Single-site, single-are, non-blinded, non-randomized, interventional

Study Record Dates

• First Submitted: August 27, 2021
• First Posted: September 16, 2021
• Study Start: December 1, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: December 21, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)