Cardiovascular Function and Response to Stimulation Within the First Year After Spinal Cord Injury

Official title

Assessing Cardiovascular Effects: Is There a Time Too Early for Spinal Stimulation in Acute SCI? A Year-Long Evaluation of Autonomic Function Following Injury

Overview

The study aims to explore how cardiovascular function changes in the first year after a spinal cord injury, and to see how different treatments, like spinal stimulation through the skin (transcutaneous spinal stimulation), affect blood pressure. The main questions are: How does stimulation affect blood pressure over the year? What is the level of cardiovascular activation throughout the year? The study will start during the inpatient stay at the Kessler Institute for Rehabilitation and continue after discharge as an outpatient, totaling about 20-29 sessions over the year.

Detailed description

This clinical study investigates the cardiovascular effects of spinal cord transcutaneous stimulation (scTS) in individuals with recent spinal cord injury (SCI), examining how blood pressure response to stimulation evolves over the first year post-injury. The primary objectives are to determine the optimal timing for initiating scTS for cardiovascular control, characterize blood pressure response evolution to stimulation over one year, and assess autonomic activation patterns through multiple testing methods.

The study will recruit five individuals with recent SCI, specifically targeting those who are 50 days or less post-injury, with an injury level at or above T6, and classified as American Spinal Injury Association Impairment Scale (AIS) A/B. All participants must present with low blood pressure and orthostatic hypotension and be between 18-75 years of age.

The study protocol is divided into inpatient and outpatient phases. During the inpatient phase, consisting of 5-11 sessions, participants undergo a basic assessment including autonomic dysfunction questionnaires, 24-hour blood pressure monitoring, cold pressor testing, and tilt tests with and without stimulation. The protocol also includes 2-3 days of stimulation mapping.

The outpatient phase spans 15-18 sessions over the remainder of the year. Participants undergo monthly mapping sessions and autonomic dysfunction assessments, with comprehensive autonomic testing conducted at 6, 9, and 12 months post-injury. Throughout both phases, researchers perform stimulation mapping across various spinal segments (thoracic, lumbosacral) using a 5-channel electrical stimulator, while monitoring blood pressure and electromyography to target a blood pressure range of 110-120 mmHg.

The study employs multiple assessment tools, including 70° tilt tests with orthostatic symptom evaluation every 5 minutes, cold pressor tests, autonomic dysfunction questionnaires, and 24-hour ambulatory blood pressure monitoring.

The study aims to track primary outcomes including blood pressure response to stimulation at different time points, evolution of orthostatic hypotension symptoms and management, and the pattern of autonomic dysfunction development post-injury.

A spin-off study is conducted to determine which cold-pressor intervention yields the most stable and consistent blood pressure response. This supplementary study compares 5 individuals with chronic SCI and 5 able-bodied controls. The findings from this spin-off study will directly inform the intervention protocol used in the main study.

Interventions

• Device spinal cord transcutaneous stimulation
  Stimulation, using the Neostim-5 (Cosyma Ltd.), a 5-channel electrical stimulator, will be administered throughout the study period, beginning shortly after the injury and continuing at regular intervals until one year post-spinal cord injury. It will be performed in two settings: 1. During seated mapping to identify stimulation sites (potentially T7/8, T11/12, L1/2, and S1/2) and determine stimulation parameters (e.g., frequency, pulse wave, amplitude) that elevate systolic blood pressure (SBP
• Procedure Ice testing
  Ice testing is performed using either a 3-minute ice-water immersion or a 3-minute ice-wrap application surrounding the foot. Each participant undergoes both the ice-water and ice-wrap conditions within the same session, separated by a 30-minute interval to allow the foot to return to baseline. Testing is conducted in both the seated and supine positions across two separate sessions, with both the cooling modality and body position randomized.

Primary outcome measures

• Systolic blood pressure in seated mapping sessions [Time frame: The procedure will be repeated throughout the year, starting shortly after the injury and occurring approximately once a month.]
• systolic blood pressure in a 70 degree tilt [Time frame: The procedure will be repeated throughout the year, starting shortly after the injury and occurring approximately every three months]

Secondary outcome measures (3)

• cold pressor test [Time frame: The procedure will be repeated throughout the year, starting shortly after the injury and occurring approximately every three months]
• 24-hour ambulatory blood pressure monitoring [Time frame: The procedure will be repeated throughout the year, starting shortly after the injury and occurring approximately once a month.]
• An autonomic dysfunction following spinal cord injury questionnaire [Time frame: The procedure will be repeated throughout the year, starting shortly after the injury and occurring approximately once a month.]

Eligibility criteria

For the main study:

Inclusion criteria

• Individuals with a spinal cord injury undergoing inpatient rehabilitation at the Kessler Institute for Rehabilitation
• Between 18-75 years old
• 7-50 days after injury
• Injury level ≥ T6 (a cervical or a high-level chest injury)
• Individuals experiencing low blood pressure after the injury
• American Spinal Injury Association Impairment Scale (AIS) A or B

Exclusion criteria

• A ventilator is needed for breathing.
• Devices such as brain/spine/nerve stimulators, a cardiac pacemaker/defibrillator, or intra-cardiac lines are present in the body.
• There is a significant disease affecting the blood vessels or signals in the heart, or a recent heart attack (myocardial infarction) has occurred.
• A new medication has been prescribed to treat blood pressure or a heart problem within the last five days (excluding midodrine).
• There is a known infection in the body (e.g., urinary tract infection) or a current illness (e.g., recent diagnosis of deep vein thrombosis (DVT) or other blood clotting issues, and/or a pressure injury that might interfere with the study).
• There is a history of seizures.
• Pregnancy.

For the spin-off study ice-water vs ice-wrap test (see description in study arms):

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Inclusion:

Age 18-75.

Inclusion for individuals with SCI:

• Injury sustained more than 6 months ago
• Injury level ≥ T6 (a cervical or a high-level chest injury)
• American spinal injury association impairment scale (AIS) A - D

Exclusion:

Foot lesions, uses a ventilator, devices such as brain/spine/nerve stimulators, significant or recent cardiovascular disease, known infection in the body

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Kessler Foundation — West Orange

Publications

• Engel-Haber E, Bheemreddy A, Bayram MB, Ravi M, Zhang F, Su H, Kirshblum S, Forrest GF. Neuromodulation in Spinal Cord Injury Using Transcutaneous Spinal Stimulation-Mapping for a Blood Pressure Response: A Case Series. Neurotrauma Rep. 2024 Sep 20;5(1):845-856. doi: 10.1089/neur.2024.0066. eCollection 2024. PMID 39391052

Identifiers

NCT: NCT06841198 · R1287-25

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗