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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Device: Targeted Epidural Spinal Stimulation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single-site, single-are, non-blinded, non-randomized, interventional
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Targeted Epidural Spinal Stimulation<br>Participants will undergo surgery to implant devices that will be used for Targeted Epidural Spinal Stimulation (TESS). | Device: Targeted Epidural Spinal Stimulation<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Orthostatic head-up tilt test | Beat-by-beat blood pressure is recorded as participants are passively tilted from a supine position to an upright position using a motorized table. | At baseline and during the testing phase, an average of 9 months | 
| Daily stimulation log | Participants will self-report the use of Targeted Epidural Spinal Stimulation (TESS). | From implant surgery through study completion, an average of 7 months | 
| Echocardiogram (Ejection Fraction) | Ultrasound will be used to assess cardiac structure and function. Ejection fraction will be recorded. | At baseline and during the testing phase, an average of 9 months | 
| Echocardiogram (Strain) | Ultrasound will be used to assess cardiac structure and function. Global longitudinal strain will be recorded. | At baseline and during the testing phase, an average of 9 months | 
| Vascular ultrasound | Flow-mediated dilation assessments will be performed using ultrasound to assess vascular structure and function. | At baseline and during the testing phase, an average of 9 months | 
| Autonomic Dysfunction Following Spinal Cord Injury (ADFSCI) Questionnaire | The ADFSCI is a 24-item self-report questionnaire. The questionnaire consists of demographics, medications, frequency/severity of symptoms during AD and hypotensive events. Higher scores indicate greater severity and frequency of AD episodes. | At baseline and during the testing phase, an average of 9 months | 
| International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) | Clinical examination used to assess the motor and sensory impairment and severity of a spinal cord injury. | At baseline and during the testing phase, an average of 9 months | 
| Respiratory function evaluation (Volume) | Respiratory function will be assessed using a spirometer while the participant performs a systematic set of breathing tasks. Volume will be recorded. | At baseline and during the testing phase, an average of 9 months | 
| Respiratory function evaluation (Flow) | Respiratory function will be assessed using a spirometer while the participant performs a systematic set of breathing tasks. Flow will be recorded. | At baseline and during the testing phase, an average of 9 months | 
| Quality of life questionnaire (WHOQOL-BREF) | The WHOQOL-BREF is a 26-item self-report questionnaire. The questionnaire covers physical and psychological health, social relationships, and environment. Higher scores indicate higher quality of life. | At baseline and during the testing phase, an average of 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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orthostatic hypotension, autonomic dysreflexia, epidural stimulation, blood pressure