Effects of Testosterone and Evoked Resistance Exercise after Spinal Cord Injury (TEREX-SCI): study protocol for a randomised controlled trial

Ashraf S Gorgey, Refka E Khalil, Ranjodh Gill, Laura C O'Brien, Timothy Lavis, Teodoro Castillo, David X Cifu, Jeannie Savas, Rehan Khan, Christopher Cardozo, Edward J Lesnefsky, David R Gater, Robert A Adler, Ashraf S Gorgey, Refka E Khalil, Ranjodh Gill, Laura C O'Brien, Timothy Lavis, Teodoro Castillo, David X Cifu, Jeannie Savas, Rehan Khan, Christopher Cardozo, Edward J Lesnefsky, David R Gater, Robert A Adler

Abstract

Introduction: Individuals with spinal cord injury (SCI) are at a lifelong risk of obesity and chronic metabolic disorders including insulin resistance and dyslipidemia. Within a few weeks of injury, there is a significant decline in whole body fat-free mass, particularly lower extremity skeletal muscle mass, and subsequent increase in fat mass (FM). This is accompanied by a decrease in anabolic hormones including testosterone. Testosterone replacement therapy (TRT) has been shown to increase skeletal muscle mass and improve metabolic profile. Additionally, resistance training (RT) has been shown to increase lean mass and reduce metabolic disturbances in SCI and other clinical populations.

Methods and analysis: 26 individuals with chronic, motor complete SCI between 18 and 50 years old were randomly assigned to a RT+TRT group (n=13) or a TRT group (n=13). 22 participants completed the initial 16-week training phase of the study and 4 participants withdrew. 12 participants of the 22 completed 16 weeks of detraining. The TRT was provided via transdermal testosterone patches (4-6 mg/day). The RT+TRT group had 16 weeks of supervised unilateral progressive RT using surface neuromuscular electrical stimulation with ankle weights. This study will investigate the effects of evoked RT+TRT or TRT alone on body composition (muscle cross-sectional area, visceral adipose tissue, %FM) and metabolic profile (glucose and lipid metabolism) in individuals with motor complete SCI. Findings from this study may help in designing exercise therapies to alleviate the deterioration in body composition after SCI and decrease the incidence of metabolic disorders in this clinical population.

Ethics and dissemination: The study is currently approved by the McGuire VA Medical Center and Virginia Commonwealth University. All participants read and signed approved consent forms. Results will be submitted to peer-reviewed journals and presented at national and international conferences.

Trial registration number: Pre-result, NCT01652040.

Keywords: BODY COMPOSITION and METABOLISM; INFLAMMATORY BIOMARKERS; MITOCHONDRIA; RESISTANCE TRAINING; SPINAL CORD INJURY; TESTOSTERONE.

Conflict of interest statement

Competing interests: None declared.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Figures

Figure 1
Figure 1
Timeline and main procedures of the TEREX-SCI trial for the RT+TRT and TRT groups during baseline 1, baseline 2, postintervention 1 and postintervention 2 for 26 persons with motor complete SCI. RT, resistance training; TEREX-SCI, Testosterone and Evoked Resistance Exercise after Spinal Cord Injury; TRT, testosterone replacement therapy.
Figure 2
Figure 2
A person with T4 motor complete SCI undergoing electrically evoked RT (left panel) and TRT using transdermal patches (right panel) as a part of a 16-week intervention.
Figure 3
Figure 3
Schematic diagram showing the process of recruitment over the 3-year period of the TEREX trial. TEREX, Testosterone and Evoked Resistance Exercise.
Figure 4
Figure 4
A representative figure of analysis for IVGTT in a person with SCI after infusion of dextrose followed by insulin 20 min later. The dextrose concentration is calculated by multiplying 0.3 g × body weight (kg) in 50% solution. Insulin concentration is determined by multiplying 0.02 units × body weight (kg). Blue line represents fasting glucose concentration, resting, following infusion and over 120 min. Red line represents the line of best fit of glucose concentration. Green line represents fasting insulin level, spike following 20 min of dextrose infusion and over 120 min. Black line represents the line of best fit for insulin concentration. IVGTT, intravenous glucose tolerance test.

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