Cardiovascular Health/Outcomes: Improvements Created by Exercise and Education in SCI (CHOICES)

Study Overview
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Brief Summary
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This study aims to determine whether body weight-supported treadmill training (BWSTT) has beneficial effects, over and above arm-cycle ergometry training (ACET) on indicators of cardiovascular disease (CVD) risk in individuals with severe spinal cord injury (SCI). After SCI, the primary cause of illness and death is CVD. Currently, preventative measures focus around increasing physical activity- especially through the use of ACET. However, ACET's capacity to improve cardiovascular health is questionable. Research has demonstrated that BWSTT, an alternative form of exercise, may be capable of improving cardiovascular health in individuals with SCI. The studies primary outcome measure is carotid-to-femoral pulse wave velocity (cfPWV) which has been shown to have prognostic value for CVD above and beyond that of other risk factors. It is hypothesised that through large muscle mass involvement and postural challenge, the physical stimuli of BWSTT will reduce cfPWV and lower CVD risk in individuals with SCI.

Detailed Description
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Purpose To determine whether body weight-supported treadmill training (BWSTT) has beneficial effects, over and above arm-cycle ergometry training (ACET), on arterial stiffness (carotid-to-femoral pulse wave velocity, cfPWV) and secondary health outcomes (cardiovascular, autonomic and metabolic indices, fitness, body composition, and quality of life) in individuals with chronic (≥ 1 year post-injury) motor-complete cervical and high-thoracic SCI. Hypothesis Through large muscle mass involvement and postural challenge, the physical and metabolic stimuli of BWSTT will reduce carotid-to-femoral pulse wave velocity (cfPWV) by 1 m/s in individuals with established risk (i.e. cfPWV ≥ norm median value of age-matched able-bodied individuals). Justification for the study Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in the SCI population. It is most commonly attributed to decreased physical activity levels; therefore strategies for decreasing CVD risk are centred on increasing physical activity. Unfortunately, the exercise-training literature in populations with SCI is limited, making it difficult to design evidence-based exercise prescriptions. ACET is widely used by individuals with SCI, but there is limited evidence on its ability to improve cardiovascular health. Given the evidence linking cardiovascular measures, specifically cfPWV, and CVD risk, an exercise prescription, which is capable of eliciting both acute cardiovascular responses and chronic cardiovascular adaptations, is crucial. BWSTT has demonstrated favorable cardiovascular adaptations, but is primarily employed in individuals with incomplete SCI due to the nature of the exercise. While preliminary evidence in individuals with complete SCI suggest it may have favorable training effects, its effectiveness in a large sample of individuals with chronic, motor-complete, severe SCI has yet to be established. Objectives Cardiovascular adaptations in individuals with SCI predispose them to complex secondary health problems. This study will use a comprehensive assessment of cardiovascular risk factors and two different exercise interventions to assist in developing cardiovascular risk profiles and determining if BWSTT has greater efficacy than traditional exercise interventions (ACET) for decreasing cardiovascular risk in individuals with high, severe SCI. Research Method This study will employ a prospective, multi-centre, randomized, controlled, single-blinded clinical trial. A total of 60 participants (20 per site) between 18-60 years of age who have sustained a motor-complete (i.e., C4-T6, AIS A or B) traumatic SCI ≥ 1 year prior will be recruited. Only individuals with cfPWV ≥ norm median value of age-matched able-bodied individuals will be eligible to participate. The primary outcome measure (cfPWV), and secondary cardiovascular and autonomic parameters will be assessed using a combination of electrocardiography, ultrasound, blood pressure, and applanation tonometry techniques. Fitness will be determined using a peak oxygen consumption test on a arm-cycle ergometer. Body composition will be determined using a dual energy x-ray absorbitrometry (DXA) scan. Metabolic indices will be determined from blood sampling. Lastly, quality of life and physical activity levels will be assessed using questionnaires. Measurements will take place at baseline (via participation in Study 1), and 3 and 6-months of exercise training. Training will involve 3, 30 - 60 minute exercise sessions per week, for 24 weeks. Both BWSTT and ACET sessions will take place at the Blusson Spinal Cord Centre at International Collaboration On Repair Discoveries (ICORD).

Official Title
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Cardiovascular Health/Outcomes: Improvements Created by Exercise and Education in SCI (CHOICES)

Conditions
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Spinal Cord Injury

Intervention / Treatment
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* Other: Body Weight Supported Treadmill Training
* Other: Arm Cycle Ergometry Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-60 years of age Motor-complete SCI (AIS A or B) Severe SCI (C4-T6) Individuals must be competent to give informed consent. cfPWV above median for age: < 30 years = 6.1 m/s 30-39 years = 6.4 m/s 40-49 years = 6.9 m/s 50-59 years = 8.1 m/s ≥ 60 years = 9.7 m/s Exclusion Criteria: History and/or symptoms of CVD or cardiopulmonary problems/disease. Major trauma or surgery within the last 6 months. Active Stage 3 or 4 pressure ulcer (based on the National Pressure Ulcer Advisory Panel classification) Recent (within 1 year) history of lower-extremity or non-union fracture Any unstable medical/psychiatric condition or substance abuse disorder that is likely to affect their ability to complete this study. Individuals with active medical issues such as pressure sores, urinary tract infections, hypertension, or heart disorders. Any cognitive dysfunction or language barrier that would prevent subjects from following English instructions. Subjects may be excluded at the discretion of the principal investigator due to other, unforeseen, safety issues. Weighing >135 kg (absolute weight capacity of the body weight-supported treadmill).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Body Weight Supported Treadmill Training<br>BWSTT protocol will consist of training of individuals with complete SCI on a treadmill with a body weight support system. BWSTT is assisted by three individuals who participate in training. One trainer provides support at the hip, and one trainer at each leg. The participant will be fitted with a harness while seated in their wheelchair and then wheeled up a ramp to the treadmill. Cables attached to the harness will be used to hoist the participant into a standing position. Appropriate body weight support will be set according to the suggested Hocoma locomotor training protocol, in which weight is added until the participant is in dynamic support as indicated by the dynamic gauge on the treadmill. Dynamic support is usually indicated at the weight where participants do not have knee-buckling during a static standing position; however, this may not be observed in all severe, motor-complete SCI participants. | Other: Body Weight Supported Treadmill Training<br>* BWSTT protocol will consist of training of individuals with complete SCI on a treadmill with a body weight support system. BWSTT is assisted by three individuals who participate in training. One trainer provides support at the hip, and one trainer at each leg. The participant will be fitted with a harness while seated in their wheelchair and then wheeled up a ramp to the treadmill. Cables attached to the harness will be used to hoist the participant into a standing position. Appropriate body weight support will be set according to the suggested Hocoma locomotor training protocol, in which weight is added until the participant is in dynamic support as indicated by the dynamic gauge on the treadmill. Dynamic support is usually indicated at the weight where participants do not have knee-buckling during a static standing position; however, this may not be observed in all severe, motor-complete SCI participants.<br>* Other names: BWSTT;|
| Active Comparator: Arm Cycle Ergometry Training<br>Arm Cycle Ergometry Training ACET will be performed on an arm-cycle ergometer against individually determined levels of resistance. Upright hand cuffs will be used so that the hand will be placed with the thumb pointing downward, and the ergometer will be positioned so that the arm never exceeded the height of the shoulder. The end objective is for the individual to complete 30-minutes of exercise in 2, 15-minute bouts. For safety reasons, stop criteria for individual sessions will be set and participants will have a rest period of 5 minutes and afterwards asked if they want to stop exercise, or resume the session. | Other: Arm Cycle Ergometry Training<br>* Arm Cycle Ergometry Training ACET will be performed on an arm-cycle ergometer against individually determined levels of resistance. Upright hand cuffs will be used so that the hand will be placed with the thumb pointing downward, and the ergometer will be positioned so that the arm never exceeded the height of the shoulder. The end objective is for the individual to complete 30-minutes of exercise in 2, 15-minute bouts. For safety reasons, stop criteria for individual sessions will be set and participants will have a rest period of 5 minutes and afterwards asked if they want to stop exercise, or resume the session.<br>* Other names: ACET;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of Body Weight Support Treadmill Training (BWSTT) on carotid-to-femoral pulse wave velocity (cfPWV) in people with Spinal Cord Injury (SCI) at 3- and 6-months of exercise. |  | cfPWV assessed at baseline, 3- and 6-months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of Body Weight Support Treadmill Training (BWSTT) on Cardiovascular parameters in people with Spinal Cord Injury (SCI) at 3- and 6-months of exercise. | Assessments of Blood Pressure & Heart Rate, Arterial Structure, Cardiac Structure & Function, Orthostatic Instability(Sit-Up Test) and 24-hr Blood Pressure Lability will be used to assess cardiovascular function. Parameters recorded from these tests include End Systolic Volume, End Diastolic Volume, Intraventricular Septum Systole (IVSs), Intraventricular Septum Diastole (IVSd), Left Ventricular Internal Diameter Systole (LVIDs), Left Ventricular Posterior Wall Systole (LVIDd), Left Ventricular Posterior Wall Diastole (LVPWd), Ejection Fraction, Cardiac Output, Fractional Shortening, Mitral Regurgitation (dP/dT), E/A, E/e' ratio, IVRT, DT, Lumen Diameter, Intima-Media Thickness, Wall/Lumen Ratio (Carotid, Brachial & Femoral), Systolic Blood Pressure, Diastolic Blood Pressure, Mean Arterial Blood Pressure and Heart Rate. | Assessed at baseline, 3- and 6-months. | 
| The effect of 6-months Body Weight Support Treadmill Training (BWSTT) on Autonomic function in people with Spinal Cord Injury (SCI). | Systolic and diastolic blood pressure, Mean Arterial Blood Pressure and Heart Rate will be measured. This outcome measure will also be assessed using the International Autonomic Standards Evaluation. | Assessed at baseline and 6-months. | 
| The effect of Body Weight Support Treadmill Training (BWSTT) on Body Composition in people with Spinal Cord Injury (SCI) following 6-months of exercise. | Body composition will be assessed using Dual Energy X-Ray Absorptiometry (DXA). DXA will be used to assess Height, Total Body Fat (Kg), Lean Mass (Kg), Body Fat Percentage and Bone Mineral Density. Weight, body mass index (BMI), Waist and Hip Circumferences will also be measured. | Assessed at baseline and 6-months. | 
| The effect of Body Weight Support Treadmill Training (BWSTT) on Metabolic and hematological parameters in people with Spinal Cord Injury (SCI) following 6-months of exercise. | Metabolic parameters will be assessed through blood analysis. Blood analysis will yield the following metabolic and hematological parameters: White Blood Cell Count, Erythrocytes, Packed Cell Volume, Hematocrit, Platelets, Hemoglobin, Red Cell Indices, glycated hemoglobin (HbA1C), Fasting Glucose, Triglycerides, Total Cholesterol, LDL-C, HDL-C, TC/HDL-C. | Assessed at baseline and 6-months. | 
| The effect of Body Weight Support Treadmill Training (BWSTT) on aerobic fitness in people with Spinal Cord Injury (SCI) following 6-months of exercise. | Aerobic fitness will be assessed via a VO2 Peak tests completed on an arm cycle ergometer. We will record Resting ECG, Blood Pressure, RPE, Oxygen Consumption and VO2Peak as well as feedback from the Positive and Negative Affect Scale (PANAS) and Visual Analogue Pain Scale. | Assessed at baseline and 6-months. | 
| The effect of Body Weight Support Treadmill Training (BWSTT) on quality of life in people with Spinal Cord Injury (SCI) at 3 months, 6 months and 12 months (6-month follow-up after the exercise intervention). | Quality of life (QoL) will be assessed through questionnaires administered centrally by Dr. Kathleen Martin-Ginis of McMaster University in Hamilton, Ontario. Questionnaires used to assess QoL are; Leisure-Time Physical Activity, Questionnaire for People with SCI, MOS-36 Pain and Health Subscales, Autonomic Questionnaire, Satisfaction with Life Scale, Life Satisfaction Questionnaire, Self-Efficacy for Aerobic Exercise, Spinal Cord Independence Measure, Impact on Participation and Autonomy Questionnaire | Assessed at baseline, 3 months, 6 months and 12 months (6 months following either intervention) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intervention, Body Weight Supported Treadmill Training, Arm Cycle Ergometry Training, carotid-to-femoral pulse wave velocity