Hybrid-FES Exercise to Prevent Cardiovascular Declines in Acute SCI

Study Overview
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Brief Summary
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Each year, 11,000 people suffer a spinal cord injury (SCI) in the U.S. Within the first year, there are profound declines in physiologic function, forming the underlying substrate for future cardiovascular disease . In fact, acquired cardiovascular disease is an increasingly recognized consequence of SCI and is the leading cause of death in SCI. Though incompletely understood, the almost 10-fold prevalence of cardiovascular disease results in part from profound physiologic 'detraining' resulting from motor impairment and immobility. Currently, effective interventions preventing acute declines that lead to cardiovascular compromise and increased risk in SCI are lacking - exercise therapy for those with SCI is challenging and when employed, is typically limited to the upper body. Recently, the investigators refined a unique form of exercise for those with SCI that specifically mirrors exercise performed by those without SCI. Functional Electrical Stimulation (FES) Row Training (RT) couples volitional arm and electrically controlled leg exercise, resulting in a hemodynamic profile that produces the beneficial cardiac loading conditions of large muscle mass exercise. As such, FES-RT may be a safe and effective way to attenuate cardiovascular declines following SCI. The investigators aims are to test the overall hypotheses that FES-RT will: 1) mitigate against increased visceral adiposity and reduced insulin sensitivity, 2) prevent worsening lipid profile and compromised baroreflex function, and 3) counter ventricular wall thickening and declining ventricular function occurring with acute SCI, and that these effects will be greater than that observed with an arms-only exercise group. Changes with FES-RT will be compared to a time (wait-list) control and to arms-only-RT. Individuals with an SCI within the last 3-6 months will be randomized to FES-RT, to a time control, or arms-only-RT. Measures will be made at baseline and 6 months. The investigators work will provide results that clearly delineate potential health benefits of FES-RT, and if FES-RT is effective in a majority of those with SCI, its application, implementation, and integration could be easily replicated.

Detailed Description
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We will enroll approximately 60 individuals within three to six months post SCI to obtain data on 50 individuals. One-half of the subjects (N=25) will be randomized to immediately enroll in 6 months of FES-RT. One third (N=18) will be randomized to a wait-list to provide time control data from baseline to 6 months. A wait-list control group is routine in exercise studies because most volunteers are interested in participating in an exercise program. Hence, time controls are difficult to capture since many of those randomized to receive no exercise either drop from the study entirely, or end up pursuing some form of exercise on their own. Therefore, a vehicle for enrollment of a time control group that is acceptable to most volunteers is a wait-list. Therefore, a six month time control will provide data on expected declines and then subjects will be randomized to six months exercise. Training Protocols for Each Study Group FES-RT GROUP Subjects will begin with short intervals of FES-RT interspersed with rest intervals and/or arms-only rowing intervals depending on fitness level and the response to the FES. A maximum FES-rowing test will be performed at baseline. This will be repeated after three months of training and training intensity will be adjusted to maintain the training stimulus at the same relative intensity. The goal is for each volunteer to achieve an exercise intensity of 75-85% maintained for a continuous 30 minutes performed three times each week. A maximum FES-rowing test will be performed at the end of the six months of FES-RT to determine increases in fitness. ARMS-ONLY-RT GROUP Training sessions will be 3 times per week for 26 weeks. To parallel the FES-RT, the initial training sessions will also consist of 6 sets of arms-only rowing for five minutes at 60% of VO2peak with a work-to-rest ratio of 2:1 and progress over the six months to an exercise intensity of 75-85% maintained for 30 minutes performed three times each week. A maximum arms-only rowing test will be performed at baseline. This will be repeated after three months of training and training intensity will be adjusted to maintain the training stimulus at the same relative intensity. A maximum arms-only rowing test will be performed at the end of the six months of training to determine increases in fitness. WAIT-LIST GROUP The wait list group will not participate in any training for 6 months. A maximum arms-only rowing test will be performed immediately after enrollment, after initial familiarization with arms-only-RT equipment (usually 2-3 sessions) and will be repeated after 3 and 6 months

Official Title
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Hybrid-FES Exercise to Prevent Cardiovascular Declines in Acute SCI

Conditions
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Spinal Cord Injury

Intervention / Treatment
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* Other: FES-row-training
* Other: Arms-only-row training
* Other: Time Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Spinal cord injured outpatients aged 18-40 medically stable body mass index 18.5-30.0 3-12 months post SCI ASIA scale A, B or C at neurological level C5-T12 able to follow directions leg muscles responsive to FES Exclusion Criteria: hypertension significant arrhythmias coronary artery disease diabetes renal disease cancer epilepsy current use of cardioactive medications current grade 2 or greater pressure ulcers at relevant contact sites other neurological disease peripheral nerve compressions or rotator cuff tears that limit ability to row history of bleeding disorder

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Three intervention groups (Control, AO-Row, and FES-RT) run in parallel
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FES-row-training<br>Subjects will perform 6 months of FES-row-training. | Other: FES-row-training<br> <br> |
| Other: Wait-list time control<br>Subjects perform 6 months of their standard of care | Other: Time Control<br> <br> |
| Active Comparator: Arms-only-row-training<br>Subjects will perform 6 months of arms-only row training | Other: Arms-only-row training<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Exercise Capacity at 6 Months | Volunteers will perform an incremental exercise test of FES- or arms-only rowing to determine maximal oxygen uptake. | Baseline and 6 months | 
| Change From Baseline in Visceral Adiposity at 6 Months | We will use a 5th generation General Electric Healthcare dual x-ray absorptiometry(DXA) scanner for regional fat measurements, the DXA software can be used to define standard regions that will allow comparability of measurements throughout the study. | Baseline, 6 months | 
| Change From Baseline in Myocardial Structure at 6 Months. | Echocardiography was performed using a commercially available system(Vivid-1, General Electric Healthcare)to obtain measures of left ventricular wall thickness and left ventricular diastolic function. | Baseline and 6 months | 
| Change From Baseline in Insulin Sensitivity at 6 Months. | Blood will be taken via standard venipuncture to measure the homeostasis model assessment of insulin resistance (HOMA-IR). HOMA-IR is a measure of insulin resistance/sensitivity calculated by multiplying fasting insulin (μU/mL) by fasting glucose (mg/dL) and divided by a constant (405). A higher value indicates higher insulin resistance. | Baseline and 6 months | 
| Change From Baseline in Blood Lipids at 6 Months | Blood will be taken via standard venipuncture to measure: total cholesterol. | Baseline and 6 months |