Cardiopulmonary Changes Following Spinal Cord Stimulation in Individuals With Spinal Cord Injury

Overview

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:

Interventions

• Device Transcutaneous Spinal Cord Stimulation (tSCS)
  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

Primary outcome measures

• Circulating endothelial biomarkers in EMV/µL (Park et al., 2023) [Time frame: Real-time Effect: 1 week; Long-term Effect: 8 weeks]

Secondary outcome measures (3)

• Plasma catecholamines in nmol/L (Claydon & Krassioukov, 2008) [Time frame: Real-time Effect: 1 week; Long-term Effect: 8 weeks]
• Spirometric parameters for lung volume in ml/kg (Aung et al., 2019) for FVC [Time frame: Real-time Effect: 1 week; Long-term Effect: 8 weeks]
• Spirometric parameters for lung volume in ml/kg (Aung et al., 2019) for FEV1 [Time frame: Real-time Effect: 1 week; Long-term Effect: 8 weeks]

Eligibility criteria

INCLUSION \& EXCLUSION CRITERIA:

Inclusion criteria

A participant must meet all of the following criteria in order to be eligible for inclusion:

• Resident of British Columbia, Canada with active provincial medical services plan
• Male or female, 19-65 years of age
• Chronic SCI at or above the T10 spinal cord segment
• >1-year post injury or diagnosis, at least 6 months from any spinal surgery.
• American Spinal Injury Association Impairment Scale (AIS) A, B, C and D for SCI
• Stable management of spinal cord related clinical issues (e.g., spasticity management)
• 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.

• 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.
• Must provide informed consent.
• 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).
• Willing and able to comply with all clinic visits and study-related procedures.

Exclusion criteria

A participant who meets any of the following criteria will not be eligible to participate:

• Ventilator dependent.
• Painful musculoskeletal dysfunction, unhealed fracture, pressure sore, or active infection that may interfere with testing
• Clinically significant, unmanaged, depression (PHQ-9 above 15) or ongoing drug abuse.
• Use of any medication or treatment that in the opinion of the investigator indicates that it is not in the best interest of the participant to participate in this study.
• Intrathecal baclofen pump.
• Cardiovascular, respiratory, bladder, or renal disease unrelated to SCI or presence of hydronephrosis or presence of obstructive renal stones.
• Presence of severe acute medical issue(s) that in the investigator's judgement would adversely affect the participant's participation in the study (e.g., pressure sore, urinary tract infection, etc.).
• Any implanted metal (other than dental implants) in the skull or presence of pacemakers, stimulators, or medication pumps in the trunk.
• Severe anemia (Hgb<8 g/dl) or hypovolemia as measured by hematocrit via blood test in the last six months.
• Participant has undergone electrode implantation surgery.
• Participant is a member of the investigational team or his/her immediate family.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 1 center

• Blusson Spinal Cord Centre — Vancouver

Publications

• Hubli M, Gee CM, Krassioukov AV. Refined assessment of blood pressure instability after spinal cord injury. Am J Hypertens. 2015 Feb;28(2):173-81. doi: 10.1093/ajh/hpu122. Epub 2014 Jul 1. PMID 24990527
• Forchheimer M, McAweeney M, Tate DG. Use of the SF-36 among persons with spinal cord injury. Am J Phys Med Rehabil. 2004 May;83(5):390-5. doi: 10.1097/01.phm.0000124441.78275.c9. PMID 15100631
• The National Health Interview Survey design, 1973-84, and procedures, 1975-83. Vital Health Stat 1. 1985 Aug;(18):1-127. No abstract available. PMID 4082502
• Ferris BG. Epidemiology Standardization Project (American Thoracic Society). Am Rev Respir Dis. 1978 Dec;118(6 Pt 2):1-120. No abstract available. PMID 742764
• Martin Ginis KA, Phang SH, Latimer AE, Arbour-Nicitopoulos KP. Reliability and validity tests of the leisure time physical activity questionnaire for people with spinal cord injury. Arch Phys Med Rehabil. 2012 Apr;93(4):677-82. doi: 10.1016/j.apmr.2011.11.005. Epub 2012 Feb 13. PMID 22336103
• Consortium for Spinal Cord Medicine. Early acute management in adults with spinal cord injury: a clinical practice guideline for health-care professionals. J Spinal Cord Med. 2008;31(4):403-79. doi: 10.1043/1079-0268-31.4.408. No abstract available. PMID 18959359
• Hubli M, Krassioukov AV. Ambulatory blood pressure monitoring in spinal cord injury: clinical practicability. J Neurotrauma. 2014 May 1;31(9):789-97. doi: 10.1089/neu.2013.3148. Epub 2014 Jan 30. PMID 24175653
• Standardization of Spirometry, 1994 Update. American Thoracic Society. Am J Respir Crit Care Med. 1995 Sep;152(3):1107-36. doi: 10.1164/ajrccm.152.3.7663792. No abstract available. PMID 7663792

Identifiers

NCT: NCT06379711 · H22-03727

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗