Clinical trial NCT05731986: Spinal Cord Transcutaneous Stimulation Effect on Blood Pressure in Acute Spinal Cord Injury (SCI)
Official title: Neuromodulation of Blood Pressure Using Transcutaneous Spinal Stimulation in Individuals With an Acute Spinal Cord Injury - A Safety, Feasibility and Efficacy Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Spinal Cord Injuries
Spinal Cord Diseases
Trauma, Nervous System
Nervous System Diseases
Central Nervous System Diseases
Hypotension
Orthostatic Hypotension
Cardiovascular Diseases
Acute Spinal Cord Injury
Blood Pressure
Keywords: Transcutaneous Spinal Cord Stimulation
Spinal stimulation
Orthostatic Hypotension
Blood Pressure
Neuromodulation
Acute spinal cord injury
Hypotension
Acute inpatient rehabilitation
Lead sponsor: Kessler Foundation
Sponsor class: OTHER
First posted: 2023-02-16
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Twelve individuals admitted to inpatient rehabilitation after sustaining a spinal cord injury will be enrolled. They will complete baseline assessments including an orthostatic sit-up test and neurophysiological mapping. Subsequently, the intervention will consist of two days of stimulation mapping to locate the optimal spinal segment for a blood pressure response. Participants will then be randomly assigned to two groups that would determine the order of the two testing days (optimal/sham), where stimulation is applied during an orthostatic test.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to evaluate the effect of transcutaneous spinal cord stimulation on blood pressure in individuals with an acute spinal cord injury (within 30 days of injury). Blood pressure instability, specifically orthostatic hypotension (a drop in blood pressure when moving lying flat on your back to an upright position), appears early after the injury and often significantly interferes with participation in the critical rehabilitation time period.

The main questions it aims to answer are:

1. Can optimal spinal stimulation increase blood pressure and resolve orthostatic symptoms (such as dizziness and nausea) when individuals undergo an orthostatic provocation (a sit-up test)? Optimal stimulation and sham stimulation (which is similar to a placebo treatment) will be compared.
2. What are the various spinal sites and stimulation parameters that can be used to increase and stabilize blood pressure to the normal range of 110-120 mmHg?

Participants will undergo orthostatic tests (lying on a bed that starts out flat and then moved into an upright seated position by raising the head of bed by 90° and dropping the base of the bed by 90° from the knee) with optimal and sham stimulation, and their blood pressure measurements will be evaluated and compared.

Detailed description: Blood pressure (BP) control in persons with a spinal cord injury (SCI) is often impaired, resulting in short and long-term health complications and a decline in quality of life. Cardiovascular (CV) dysfunction develops early after SCI and often continues a lifetime. Orthostatic hypotension (OH), a 20/10 mmHg decrease in systolic/diastolic BP when moving from a supine to an upright position, is especially prevalent in the early phase, and frequently accompanied by symptoms of dizziness, weakness, fatigue, and syncope. Affecting up to 75% of therapy treatments during inpatient rehabilitation, OH significantly interferes with participation during the critical rehab time-period, especially as length of stay in rehabilitation has substantially shortened in the past decades.

The compelling rationale for early identification and treatment of OH is met by several pharmacological and non-pharmacological interventions, however, the majority have limited effect, and increase the risk of adverse drug effects due to polypharmacy. In recent years, epidural and transcutaneous spinal cord stimulation has been explored with promising results as a potential treatment to CV dysfunction in SCI. To date, only individuals with a chronic SCI (\>1 year) were included in these studies.

The objective of this study is to investigate the effect of spinal cord transcutaneous stimulation (scTS) on BP in individuals with an acute/sub-acute SCI (7-30 days after injury), during their inpatient rehabilitation. Optimal stimulation sites and parameters that increase and stabilize systolic BP (SBP) within the normotensive range (110-120 mmHg) during an orthostatic challenge will be sought. In this crossover randomized controlled trial (RCT), the effect of optimal CV stimulation and sham stimulation on BP and orthostatic symptoms will be assessed and compared.

The information gleaned from this work will allow design and implementation of scTS interventions in the early phase following an SCI, allowing full participation in inpatient rehabilitation programs, which are often hindered by the patients' autonomic dysfunction.

Eligibility criteria: Inclusion Criteria:

* 7-30 days after injury
* Injury level ≥T2 (thoracic level)
* American Spinal Injury Association Impairment Scale (AIS) A-C
* Exhibits at least one of the following hypotensive symptoms:

  1. Baseline hypotension - resting supine or seated SBP \< 90mmHg;
  2. SBP drop ≥ 20 mmHg within 5 minutes of assuming seated position;
  3. Symptoms of orthostasis with a drop of SBP (\<90mmHg) from supine to sitting.

Exclusion Criteria:

* Current illness (e.g., a recent diagnosis of a deep vein thrombosis (DVT) or pulmonary embolism (PE), a pressure injury that might interfere with the intervention, etc.) or infection
* Ventilator-dependent
* History of implanted brain/spine/nerve stimulators
* Cardiac pacemaker/defibrillator or intra-cardiac lines
* Significant coronary artery or cardiac conduction disease, a recent history of myocardial infarction
* Initiated on new cardiac medications within the past 5 days
* Insufficient mental capacity to understand and independently provide consent
* Pregnancy
* Cancer
* Deemed unsuitable by study physician

Primary outcomes:
measure: Optimal stimulation sites
timeFrame: Through Mapping and testing sessions, average of 2 weeks
measure: Optimal stimulation frequency
timeFrame: Through Mapping and testing sessions, average of 2 weeks
measure: Systolic blood pressure measurements (mmHg) - Mean and SD of beat-to-beat BP
timeFrame: Throughout the experiment, average of 2 weeks
measure: Change in Orthostatic symptoms when stimulation is applied
timeFrame: Will be performed every 5 minutes during the orthostatic tests, average of 2 weeks
Secondary outcomes:
measure: Numeric Rating Scale (NRS) for pain
timeFrame: Throughout the experiment, average of 2 weeks
measure: Skin integrity assessment
timeFrame: Throughout the experiment, average of 2 weeks
measure: Feasibility of applying scTS in inpatient settings - compliance
timeFrame: Throughout the experiment, average of 2 weeks
measure: Feasibility of applying scTS in inpatient settings - session duration
timeFrame: Throughout the experiment, average of 2 weeks
measure: Feasibility of applying scTS in inpatient settings - effect on therapy
timeFrame: Throughout the experiment, average of 2 weeks
measure: Electromyography (EMG) of leg muscles - muscle activation (analysis of mean and peak amplitudes)
timeFrame: Through Mapping and testing sessions, average of 2 weeks
measure: Additional hemodynamic measure - diastolic blood pressure
timeFrame: throughout the trial, average of 2 weeks
measure: Additional hemodynamic measure - heart rate
timeFrame: throughout the trial, average of 2 weeks
Other outcomes:
Locations:
city: West Orange
country: United States
facility: Kessler Foundation
state: New Jersey
Study officials:
affiliation: Kessler Foundation
name: Gail F Forrest, PhD
role: PRINCIPAL_INVESTIGATOR
References: