Testosterone Replacement Therapy in Chronic Spinal Cord Injury

Study Overview
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Brief Summary
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It has long been recognized that co-morbidity associated with multiple metabolic syndrome, such as adverse body composition, insulin resistance and autonomic nervous system impairment, may lead to significant increase in cardiovascular morbidity and mortality. It is unclear whether the co-morbidity evident in this population are due directly to their immobility or are the result of unfavorable changes in their underlying hormonal milieu. The purpose of this study is to determine the effect of testosterone replacement therapy in hypogonadal males on: body composition, i.e. lean tissue and fat mass, glucose tolerance, resting energy expenditure, autonomic-cardiovascular integrity, muscular strength, psychological assessment

Detailed Description
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This study is 24 months in duration. Men who have consented to pre-screening serum testosterone draw and are found to have total testosterone levels averaging ≤ 11.3 nmol/l will start testosterone replacement therapy after a 6-month baseline period. Once treatment begins subjects will place a testosterone replacement patch (5 or 10 mg/day) on various sites of the body daily. Subjects will visit the lab after 2,6, 12, and 18 months of therapy for testing; however they will stop taking the patch at the 12 month visit. If needed, a steroid cream will be provided to the subjects should any skin irritations occur. If the patch causes persistent skin irritations, despite use of the steroid cream, then a testosterone gel may be used. Detailed instructions and precautions using the gel are outlined in the consent form and will be reviewed with the subject. Those men who have consented to pre-screening serum testosterone and are found to have normal levels of total testosterone (testosterone total ≥ 11.4 nmol/l) are eligible to participate as a control subject for the full 24-month period of the study. These subjects visit the lab at baseline (BL), 12 and 24 months for the same testing as those in the treatment group.

Official Title
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Testosterone Replacement Therapy in Chronic Spinal Cord Injury

Conditions
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Spinal Cord Injury, Hypogonadism

Intervention / Treatment
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* Drug: Testosterone Transdermal System (Androderm 5 mg patch)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males 18-49 years of age Chronic spinal cord injury Normal prostate specific antigen levels and digital rectal exam No known cardiovascular disease Subjects with total testosterone > 4 ng/ml Subjects with total testosterone > 4 ng/ml Exclusion Criteria: Females Known coronary heart and/or artery disease, diabetes mellitus Previous or current cancer Current or previous anabolic steroid use Acute inter-current illness Abnormal liver function test (>1.5 times normal values) at baseline Prostate specific antigen above normal Abnormal digital rectal exam at baseline suggestive of malignancy Current alcohol or drug abuse Significant psychological disorders

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Male

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Testosterone Replacement Therapy<br>Subjects with Low Testosterone (Hypogonadal) Receive Testosterone Transdermal System (Androderm 5 mg patch) | Drug: Testosterone Transdermal System (Androderm 5 mg patch)<br>* Testosterone Transdermal System (Androderm 5 mg patch)<br>* Other names: Androgel (Testim) and Underarm Testosterone (Axiron);|
| No Intervention: No Intervention<br>Subjects with normal testosterone levels (eugonadal) participated in identical outcome measurements at parallel time points. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dual Energy X-ray Absorptiometry (DXA) Assessment of Lean Tissue Mass (LTM) | Dual energy X-ray absorptiometry assessment of lean tissue mass (LTM) at 12 months. Total body scans were performed and the energy level used for each total body scan was based on subject thickness (e. g., thin, standard, or thick). To analyze the results of each total body scan, proprietary software algorithms were used to segment the body into trunk, pelvis, and upper and lower extremities using the standard regions of interest. In accordance with International Society for Clinical Densitometry guidelines, total body scans were repeated on 30 spinal cord injury subjects by the on-and-off -the-table method (i. e., subjects were repositioned between scans) and our precision error was equal to 1.2 % for LTM. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting Energy Expenditure | Resting Energy Expenditure was obtained by the measurement of exhaled air from fractions of mixed expired oxygen and carbon dioxide by a process known as indirect calorimetry. Data was collected under steady state conditions. Participants arrived at the laboratory for testing between the hours of 8:00 and 10:00 in the morning, following a 12-h fast, with a minimum of 24 h free from any type of exercise. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal Cord Injury, Testosterone Replacement Therapy, Dual Energy X ray Absorptiometry, Lean Tissue Mass