Clinical trial NCT05044923: Restoring Hemodynamic Stability Using Targeted Epidural Spinal Stimulation Following Spinal Cord Injury
Official title: Restoring Hemodynamic Stability Using Targeted Epidural Spinal Stimulation Following Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Spinal Cord Injuries
Keywords: orthostatic hypotension
autonomic dysreflexia
epidural stimulation
blood pressure
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2021-09-16
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-site, single-are, non-blinded, non-randomized, interventional
Primary purpose: TREATMENT

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.

Detailed description: Clinical management of chronic hemodynamic instability is currently limited to long-acting pressor agents and anti-hypertensives. These drugs have significant limitations as they require roughly one hour to become active and exert prolonged influences on the cardiovascular system. This slow timescale contrasts with the hemodynamic instability experienced by people with spinal cord injury, which occurs most commonly over just a few minutes, and tends to cease abruptly. This study will investigate a new therapy for managing hemodynamic instability in individuals with spinal cord injury: Targeted Epidural Spinal Stimulation (TESS).

Here, the investigators propose 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 feasibility study is to provide preliminary safety and efficacy measures on the ability of the hemodynamic TESS to ensure the long-term management of hemodynamic instability and reduce the incidence and severity of orthostatic hypotension and autonomic dysreflexia episodes in humans with chronic cervical or high-thoracic spinal cord injury. In addition, the investigators aim to evaluate the long-term safety and efficacy of TESS on cardiovascular health, respiratory function, spasticity, trunk stability, sleep and quality of life in participants with chronic spinal cord injury.

The HEMO Trial will implant 4 participants with chronic (\>12 months) spinal cord injury located between C3 and T6 who have confirmed severe orthostatic hypotension and autonomic dysreflexia. Enrolled participants will undergo baseline assessments, after which they will be implanted with the investigational system. Participants will then proceed to one month of an intensive device configuration protocol to configure the TESS settings of their investigational device to regain hemodynamic stability. After the intensive device configuration phase, daily supervised at-home hemodynamic TESS will be conducted for two weeks. Thereafter, and up to 25 weeks post-implant, participants will conduct supported at-home sessions as well as regular laboratory visits during a long-term at-home hemodynamic TESS phase. Finally, participants will undergo additional testing during a configuration of additional TESS programs phase. During this phase TESS configurations for hemodynamic stability, respiratory function, trunk stability and spasticity will be tested. Several clinical evaluations are planned to evaluate participants' hemodynamic and neurological status, cardiovascular functional status, respiratory function, trunk stability, and quality of life.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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
timeFrame: From implant surgery through study completion, an average of 7 months
Secondary outcomes:
measure: Orthostatic head-up tilt test
timeFrame: At baseline and during the testing phase, an average of 9 months
measure: Daily stimulation log
timeFrame: From implant surgery through study completion, an average of 7 months
measure: Echocardiogram (Ejection Fraction)
timeFrame: At baseline and during the testing phase, an average of 9 months
measure: Echocardiogram (Strain)
timeFrame: At baseline and during the testing phase, an average of 9 months
measure: Vascular ultrasound
timeFrame: At baseline and during the testing phase, an average of 9 months
measure: Autonomic Dysfunction Following Spinal Cord Injury (ADFSCI) Questionnaire
timeFrame: At baseline and during the testing phase, an average of 9 months
measure: International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI)
timeFrame: At baseline and during the testing phase, an average of 9 months
measure: Respiratory function evaluation (Volume)
timeFrame: At baseline and during the testing phase, an average of 9 months
measure: Respiratory function evaluation (Flow)
timeFrame: At baseline and during the testing phase, an average of 9 months
measure: Quality of life questionnaire (WHOQOL-BREF)
timeFrame: At baseline and during the testing phase, an average of 9 months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
Study officials:
affiliation: University of Calgary
name: Aaron Phillips, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: 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.
citation: 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.
citation: 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.
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citation: 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.
citation: 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.
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