Hypogonadism, Spinal Cord Injury
Conditions
Keywords
Spinal Cord Injury, Testosterone Replacement Therapy, Dual Energy X ray Absorptiometry, Lean Tissue Mass
Brief summary
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
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.
Interventions
DRUGTestosterone Transdermal System (Androderm 5 mg patch)
Testosterone Transdermal System (Androderm 5 mg patch)
Sponsors
Kessler Institute for Rehabilitation
VA Office of Research and Development
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 49 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dual Energy X-ray Absorptiometry (DXA) Assessment of Lean Tissue Mass (LTM) | 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Resting Energy Expenditure | 12 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Testosterone Replacement Therapy Subjects with Low Testosterone (Hypogonadal) Receive Testosterone Transdermal System (Androderm 5 mg patch) | 13 |
| No Intervention Subjects with normal testosterone levels (eugonadal) participated in identical outcome measurements at parallel time points. | 11 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Testosterone Replacement Therapy | No Intervention | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 11 Participants | 24 Participants |
| Dual energy x-ray absorptiometry (DXA) for lean tissue mass | 49.6 kilograms STANDARD_DEVIATION 7.6 | 51.9 kilograms STANDARD_DEVIATION 8.1 | 50.8 kilograms STANDARD_DEVIATION 7.8 |
| Region of Enrollment United States | 13 participants | 11 participants | 24 participants |
| Resting Energy Expenditure | 1328 kcal/day STANDARD_DEVIATION 262 | 1319 kcal/day STANDARD_DEVIATION 112 | 1324 kcal/day STANDARD_DEVIATION 197 |
| Sex/Gender, Customized Male | 13 participants | 11 participants | 24 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / 18 |
| serious Total, serious adverse events | 1 / 18 |
Outcome results
Primary
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone Replacement Therapy | Dual Energy X-ray Absorptiometry (DXA) Assessment of Lean Tissue Mass (LTM) | 53.1 kilograms | Standard Deviation 6.9 |
| No Intervention | Dual Energy X-ray Absorptiometry (DXA) Assessment of Lean Tissue Mass (LTM) | 50.5 kilograms | Standard Deviation 6.3 |
Comparison: Separate 2 factor (group: treatment, control) analysis of variance (ANOVA) with repeated measures on visit (baseline, month 12) were performed to identify changes in lean tissue mass across time. To further characterize significant main and interaction effects, post-hoc paired t -tests were performed within group.p-value: <0.01ANOVA
Secondary
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone Replacement Therapy | Resting Energy Expenditure | 1440 kcal/day | Standard Deviation 262 |
| No Intervention | Resting Energy Expenditure | 1339 kcal/day | Standard Deviation 128 |
Comparison: Separate 2 factor (group: treatment, control) analysis of variance (ANOVA) with repeated measures on visit (baseline, month 12) were performed to identify changes in resting energy expenditure across time. To further characterize significant main and interaction effects, post-hoc paired t -tests were performed within group.p-value: 0.051ANOVA