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 patients 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 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 humans with chronic cervical or high-thoracic spinal cord injury. In addition, the long-term safety and efficacy of TESS on cardiovascular health, respiratory function, spasticity, trunk stability and quality of life in patients with chronic spinal cord injury will be evaluated.

Detailed Description
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The investigators hypothesize that Targeted Epidural Spinal Stimulation (TESS) foreshadows a new era in the hemodynamic management of both acute and chronic SCI. It is envisioned that TESS will become the first-line treatment for hemodynamic instability in people with chronic SCI, where vasopressor agents and compression garments will become second-line treatments behind the precise control of blood pressure achieved with TESS. In this study, the investigators propose to investigate the preliminary safety of hemodynamic TESS to modulate pressor responses and manage blood pressure instability in 4 patients with chronic SCI located between C3 and T6 and who suffer from severe orthostatic hypotension. The study intervention consists of 8 phases preceded by pre-screening: Screening and enrolment Baseline and pre-implantation assessments Surgery Intensive TESS Configuration phase Daily supervised at-home TESS phase Long-term at-home phase Configuration of additional TESS programs phase End of study Measures will be performed before surgical intervention and at regular intervals during the study. The study will take place at the CHUV (Lausanne, Switzerland). A total of 4 participants will be enrolled in the study and implanted with two lead electrodes (Specify Surescan 5-6-5 Leads, Model 977C190 Medtronic) and two implantable pulse generators (Intellis™ with AdaptiveStim™, Model 97715 Medtronic). All participants will undergo the same treatment and procedures. The total duration of the study will be approximately 2 months (up to 10 months/participant).

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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* Procedure: Device implantation


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 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: Patients in an emergency situation 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 rehabilitation program in the judgement of the investigators Clinically significant mental illness in the judgment of the investigators Botulinum toxin injections in the previous 6 months Presence of significant pressure ulcers Recurrent urinary tract infection refractory to antibiotics Current pregnancy Current breastfeeding Known or suspected drug or alcohol abuse 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-arm, 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 a surgery for Targeted Epidural Spinal Stimulation (TESS). The neurostimulation system will be used to manage blood pressure instability. Patients 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 tested for 5 sessions per week for two weeks. Thereafter, and up to 10 months post-implant, patients will have a minimum of 5 TESS supported at-home sessions per week and one laboratory visit per month during a long-term at-home hemodynamic TESS phase. Finally, patients will have to 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. | Procedure: Device implantation<br>* The intervention involves the insertion of 2 lead electrodes (Specify Surescan 5-6-5 Leads, Model 977C190 Medtronic) epidurally over the dorsal aspect of the spinal cord through 2 laminectomies and two implantable pulse generators (Intellis™ with AdaptiveStim™, Model 97715 Medtronic) in the abdomen 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 patients with chronic SCI located between C3 and T6 and who suffer from severe orthostatic hypotension (n=4). | From implantation through study completion, an average of 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ISNCSCI (International Standards for Neurological Classification of Spinal Cord Injury) | Clinical examination used to assess the motor and sensory impairment and severity of a spinal cord injury. | At baseline and during the rehabilitation phase, an average of 7 months | 
| Spasticity clinical exam using the Modified Ashworth Scale (MAS) | Patient's limb spasticity levels (5-point nominal scale) are assessed by rating the resistance of a muscle to a passive range of motion about a single joint. Scores range from 0 to 4 with higher scores indicating higher spasticity. | At baseline and during the rehabilitation phase, an average of 7 months | 
| Spasticity isokinetic quantification | A dynamometer (Cybex) is used to evaluate the effect of stimulation on spasticity of the hip, knee and ankle. An extension and flexion movement is performed around each joint (dynamometer in isokinetic mode). | At baseline and during the rehabilitation phase, an average of 7 months | 
| Spasticity isokinetic quantification | An extension and flexion movement is performed around each joint. EMG data is recorded through each movement. | At baseline and during the rehabilitation phase, an average of 7 months | 
| Trunk stability | The patient is asked to perform a systematic set of reaching movements while seated freely (without a back-rest). Additionally, the patient is asked to perform a set of movements deemed functionally relevant, for example reaching for an object behind them or picking up an object from the ground. Each movement is repeated and EMG data can be acquired. | At baseline and during the rehabilitation phase, an average of 7 months | 
| Respiratory function evaluation | The respiratory function is evaluated using a spirometer. Volume is recorded. | At baseline and during the rehabilitation phase, an average of 7 months | 
| Respiratory function evaluation | The respiratory function is evaluated using a spirometer. Flow is recorded. | At baseline and during the rehabilitation phase, an average of 7 months | 
| Orthostatic head-up tilt test | Patients begin by resting in the supine position during which a baseline recording is performed. Thereafter, patients will be passively moved to upright position using the tilt-table. Between each experimental condition, the patient will be moved back in supine position to return to baseline. Beat-to-beat blood pressure will be monitored. | At baseline and during the rehabilitation phase, an average of 7 months | 
| Autonomic Dysfunction Following Spinal cord injury (ADFSCI) | The ADFSCI questionnaire is a 24-item self-reported questionnaire. The questionnaire consists of demographics, medications, frequency/severity of symptoms during AD and hypotensive events. Higher scores indicate more severe and more frequent symptoms during AD and hypotensive events. | At baseline and monthly during the rehabilitation phase, an average of 7 months | 
| Quality of Life questionnaire WHOQOL-BREF | The WHOQOL-BREF is a questionnaire used to assess the quality of life. Scores are converted to range between 4-20 or 0-100 and are scaled in a positive direction: higher scores denote higher quality of life. | At baseline and monthly during the rehabilitation phase, an average of 7 months | 
| Completion of a Daily Stimulation Log (DSL) by the patient | The patient will be asked to self-report the use of TESS during the at-home phases. This information will be used to evaluate hemodynamic TESS-supported at-home stimulation sessions and characterize the use of the investigational system at home. | From daily at-home supervised used until the end of the study, an average of 5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCI, Spinal Cord Injury, Epidural Spinal Stimulation