Cardiopulmonary Diseases, Cardiovascular Diseases, Spinal Cord Injuries
Conditions
Keywords
Spinal Cord Stimulation, Transcutaneous Spinal Cord Stimulation, Cardiovascular dysfunction, Cardiopulmonary dysfunction, Cardiovascular Biomarkers, Endothelial cell-derived Microvesicles, Plasma Catecholamines, Autonomic Dysreflexia, Orthostatic Hypotension
Brief summary
The aim of this study is to examine the mechanisms of transcutaneous spinal cord stimulation (tSCS) for improving cardiovascular and pulmonary function in individuals with chronic motor-complete spinal cord injury (SCI) by measuring vascular related endothelial biomarkers, plasma catecholamines, and respiratory parameters.
Detailed description
DETAILED RESEARCH PROCEDURES (A) INFORMED CONSENT: Prospective participants will be provided with the study informed consent form and will be given at least 24 hours to review the form, ask questions, and discuss with whomever they like. (B) VISIT 1 -Screening Approximately 1 hour Individuals who agree to participate in the study will be invited for a screening assessment to confirm study eligibility. After the individual has provided informed consent, they will be assigned a unique study identification number and the information listed below will be collected. Screening questionnaires and assessments: * Inclusion/Exclusion Criteria confirmation * Demographics * Medical history and history of injury * Concomitant medication use * Weight and height * Previous allergies and adverse events to medications * Pregnancy screening will be performed * Internationals Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam (C) VISITS 2-5 -Baseline functional assessments, questionnaires, and cardiopulmonary assessments Approximately 2 hours per visit Enrolled participants will complete questionnaires after which a spirometry assessment for pulmonary function will be performed. Participants will be provided with a 24-hour Ambulatory Blood Pressure Monitor (24- ABPM) device to take home to record daily changes in cardiovascular parameters. Questionnaires (Visit 2): * Short-form (36) Health Survey (SF-36) * Autonomic Dysfunction following SCI (ADFSCI) questionnaire * Leisure Time Physical Activity Questionnaire after SCI (LTPAQ-SCI). * National Health Interview Survey - Chronic Conditions * American Thoracic Society (ATS) Adult Respiratory Disease Survey. - Tobacco Use Baseline cardiopulmonary and optional functional assessments (with and without tSCS) (Visits 2-5): * Spirometry testing (Visit 2) * 24-hour Ambulatory Blood Pressure and electrocardiogram Monitoring (24-hr ABP and ECG Monitor) (Visit 2) * Somatosensory evoked potentials (Visit 3, optional) * Transcranial Magnetic Stimulation (Visit 4, optional) * H-reflex (Visit 5, optional) * Compound Muscle Action Potentials (Peripheral nerve stimulation) (Visit 5, optional) * Muscle Ultrasound (Visit 5, optional) Participants will also be provided with instructions to prepare for Visit 3 or 6 (depending on whether they do the optional assessments), during which blood samples will be collected. Participants will be asked to: * Arrive for testing in a fasted state (fasted for 12 hours, but they may continue to drink water) * Not consume caffeine, recreational drugs, alcohol, smoking, or antihypotensive drug (e.g., midodrine) for 12 hours prior to their appointment * No strenuous exercise within 24 hours of the start of the study. (D) VISITS 3-5 or 6-8 (depending on whether or not the optional functional assessments were completed earlier in the study). Baseline cardiovascular assessments and blood draws. Approximately 3 hours In this session, participants will return the 24-hour ABP and ECG Monitor and undergo baseline cardiovascular assessments as well as the blood draws. The participant has the option of only taking part in one or all cardiovascular assessments. If the participant chooses to undergo more than one cardiovascular assessment they will be conducted on different visits. Cardiovascular Assessments: • Cardiovascular stress test (orthostatic stress test and/or vibrostimulation or DARS) Blood Draws: Four (4) blood draws will be taken: 1. At rest without tSCS 2. At rest with tSCS 3. During cardiovascular stress test without tSCS 4. During cardiovascular stress test with tSCS (E) TREATMENT VISITS (minimum 12 tSCS visits, depending on whether or not the optional functional and cardiovascular assessments were done earlier in the study) to completion of long-term intervention with tSCS intervention: Each session will last approximately 90 minutes (set-up AND at least 45min of tSCS treatment). Long-term tSCS is scheduled to last for a minimum of two times per week for 6 weeks. Following the completion of the intervention, participants will begin post-intervention questionnaires and cardiopulmonary assessments. Week to week variation in the number of scheduled sessions may vary due to varying circumstances (e.g., scheduling, transportation, participant health). However, the total number of sessions conducted will be the same as the participant's original goal. (F) SECOND TO LAST VISIT: Post-intervention questionnaires and cardiopulmonary assessment: Approximately 2 hours In this session, participants will complete post-intervention questionnaires and undergo post-intervention cardiopulmonary assessments. Questionnaires: * Short-form (36) Health Survey (SF-36) * Autonomic Dysfunction following SCI (ADFSCI) questionnaire * Leisure Time Physical Activity Questionnaire after SCI (LTPAQ-SCI). * National Health Interview Survey - Chronic Conditions * American Thoracic Society (ATS) Adult Respiratory Disease Survey. - Tobacco Use Cardiopulmonary Assessments: * Spirometry testing * 24-hour ABP and ECG Monitor (G) LAST VISIT: Post-intervention cardiovascular assessments and blood draws: Approximately 3 hours In this session, participants will undergo post-intervention cardiovascular assessments as well as the blood draws. Cardiovascular Assessments: * Carotid and cardiac ultrasound * Cardiovascular stress test (orthostatic hypotension stress and/or vibrostimulation or DARS) Blood Draws: Four (4) blood draws will be taken: 1. At rest without tSCS 2. At rest with tSCS 3. During a cardiovascular stress without tSCS 4. During a cardiovascular stress with tSCS
Interventions
Transcutaneous spinal cord stimulation (tSCS) will be delivered via a non-invasive central nervous system stimulator TESCoN or SCONE (SpineX Inc., CA - experimental type II medical devices) through self-adhesive electrode(s) placed on the skin between spinous processes over the midline of the vertebral column as the cathode(s) and two rectangular electrodes placed symmetrically on the skin over the iliac crests as anodes. Stimulation will be applied at various waveforms and frequencies (ranging between 1Hz and 90Hz) with and without a carrier frequency. Current amplitude will start at 10mA and proceed incrementally until tolerable or responses plateau. If spasticity occurs or is uncomfortable, the current will be decreased. Specific areas for electrode placement will be examined and prepared to reduce skin impedance. tSCS will be delivered under the supervision of a physician (Dr. Krassioukov/Dr. Berger) by trained doctoral/post-doctoral trainees.
Sponsors
University of British Columbia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Pre-Post Study
Eligibility
Sex/Gender
ALL
Age
19 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
INCLUSION &
Exclusion criteria
INCLUSION CRITERIA: A participant must meet all of the following criteria in order to be eligible for inclusion: 1. Resident of British Columbia, Canada with active provincial medical services plan 2. Male or female, 19-65 years of age 3. Chronic SCI at or above the T10 spinal cord segment 4. \>1-year post injury or diagnosis, at least 6 months from any spinal surgery. 5. American Spinal Injury Association Impairment Scale (AIS) A, B, C and D for SCI 6. Stable management of spinal cord related clinical issues (e.g., spasticity management) 7. Women of childbearing potential must not be intending to become pregnant, currently pregnant, or lactating. The following conditions apply: 7.1 Women of childbearing potential must have a confirmed negative pregnancy test prior to the baseline visit. 7.2 Women of childbearing potential must agree to use adequate contraception during the period of the trial and for at least 28 days after completion of treatment. Effective contraception includes abstinence. 8. Sexually active males with female partners of childbearing potential must agree to use effective contraception during the period of the trial and for at least 28 days after completion of treatment. 9. Must provide informed consent. 10. Able to understand and complete study-related questionnaires (must be able to understand and speak English or have access to an appropriate interpreter as judged by the investigator). 11. Willing and able to comply with all clinic visits and study-related procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Circulating endothelial biomarkers in EMV/µL (Park et al., 2023) | Real-time Effect: 1 week; Long-term Effect: 8 weeks | Real-time Effect: Change in circulating endothelial biomarkers (i.e., endothelial cell derived microvesicles (EMVs)) before and after real-time tSCS during cardiovascular stress (i.e., head-up tilt test to trigger orthostatic hypotension OH and/or vibrostimulation/DARS to trigger AD). Long-term Effect: Change from baseline in circulating endothelial biomarkers (i.e., endothelial cell derived microvesicles (EMVs)) before and after long-term tSCS intervention during cardiovascular stress (i.e., head-up tilt test to trigger OH and/or vibrostimulation/DARS to trigger AD). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma catecholamines in nmol/L (Claydon & Krassioukov, 2008) | Real-time Effect: 1 week; Long-term Effect: 8 weeks | Real-time Effect: Change in plasma catecholamines (e.g., norepinephrine) before and after real-time tSCS during cardiovascular stress (i.e., head-up tilt test to trigger orthostatic hypotension OH and/or vibrostimulation/DARS to trigger AD). Long-term Effect: Change from baseline in plasma catecholamines (e.g., norepinephrine) before and after long-term tSCS intervention during cardiovascular stress (i.e., head-up tilt test to trigger OH and/or vibrostimulation/DARS to trigger AD). |
| Spirometric parameters for lung volume in ml/kg (Aung et al., 2019) for FVC | Real-time Effect: 1 week; Long-term Effect: 8 weeks | Real-time Effect: Change in spirometric parameters (i.e., forced vital capacity (FVC)), before and after real-time tSCS during cardiovascular stress (i.e., head-up tilt test to trigger orthostatic hypotension OH and/or vibrostimulation/DARS to trigger AD). Long-term Effect: Change from baseline in spirometric parameters (i.e., forced vital capacity (FVC)), before and after long-term tSCS intervention during cardiovascular stress (i.e., head-up tilt test to trigger OH and/or vibrostimulation/DARS to trigger AD). |
| Spirometric parameters for lung volume in ml/kg (Aung et al., 2019) for FEV1 | Real-time Effect: 1 week; Long-term Effect: 8 weeks | Real-time Effect: Change in spirometric parameters (i.e., forced expiratory volume (FEV) in 1 second (FEV1)), before and after real-time tSCS during cardiovascular stress (i.e., head-up tilt test to trigger orthostatic hypotension OH and/or vibrostimulation/DARS to trigger AD). Long-term Effect: Change from baseline in spirometric parameters (i.e., forced expiratory volume (FEV) in 1 second (FEV1)), before and after long-term tSCS intervention during cardiovascular stress (i.e., head-up tilt test to trigger OH and/or vibrostimulation/DARS to trigger AD). |
Countries
Canada
Contacts
Primary ContactAndrea Maharaj, BSc
Outcome results
None listed