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| ID | Type | Description | Link |
|---|---|---|---|
| CX000906 | Other Grant/Funding Number | VA CSRD |
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| Name | Class |
|---|---|
| Michael E. DeBakey VA Medical Center | FED |
| Baylor College of Medicine | OTHER |
| Biomedical Research Institute of New Mexico | OTHER |
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The prevalence of obesity in Veterans is greater than in the general population, and even more so among users of the VA Health Care System. In addition, the population of obese older Veterans is rapidly increasing as more baby boomers become senior citizens. In older Veterans, obesity exacerbates the age- related decline in physical function and causes frailty which predisposes to admission to a VA chronic care facility. However, the optimal clinical approach to obesity in older adults is controversial because of the concern that weight loss therapy could be harmful by aggravating the age-related loss of muscle mass and bone mass. In fact, the MOVE (Managing Overweight/Obese Veterans) program does not have any guidelines for eligible Veterans if they are 70 or older. It is possible that the addition of testosterone replacement to lifestyle therapy will preserve muscle mass and bone mass and reverse frailty in obese older Veterans and thus prevent their loss of independence and decrease demand for VA health care services.
Obesity is not only highly prevalent among Americans, but even more so among Veterans using VA medical facilities. Failure to assist Veterans in managing weight and sedentary lifestyle affects current treatment and increases future demand for VA health care services. Decreased muscle mass with aging and the need to carry extra mass due to obesity make it particularly difficult for obese older Veterans to function independently and results in frailty leading to increased nursing home admissions and increased morbidity and mortality. Data from preliminary studies showed that lifestyle therapy resulting in weight loss in this understudied population improves physical function and ameliorates frailty. However, this improvement in physical function is modest at best and most obese older adults remain physically frail. More importantly, there are concerns that lifestyle therapy may exacerbate underlying sarcopenia and osteopenia from weight loss- induced loss of lean body mass and bone mineral density (BMD). As a result, most geriatricians are reluctant to recommend lifestyle therapy that includes weight loss in obese frail elderly patients although the combination of weight loss and exercise is recommended as part of standard care for obese patients in general. Thus, it is not surprising that among Veterans, the MOVE (Managing Overweight/Obese Veterans) program does not have any guidelines for eligible Veterans if they are 70 or older. In addition to overeating and lack of exercise, age-related decline in anabolic hormone (i.e. testosterone) may contribute to sarcopenia and osteopenia, which in turn is exacerbated by obesity. Indeed, preliminary studies discovered that obese older men had markedly low levels of serum testosterone at baseline which remained low throughout the duration of lifestyle therapy. Because testosterone replacement therapy has been shown to increase muscle mass and BMD, it is therefore likely that concomitant testosterone replacement during lifestyle therapy in obese older adults would preserve lean body mass and BMD, and reverse frailty. Accordingly, the optimal management to the problem of sarcopenic obesity and frailty might require a comprehensive approach of a combination of lifestyle intervention and the correction of anabolic hormone deficiency. Therefore, the primary goal of this proposal is to conduct a randomized, comparative efficacy, double-blind, placebo-controlled (for testosterone) trial of the effects of 1) lifestyle therapy (1% diet-induced weight loss and exercise training) + testosterone replacement therapy versus 2) lifestyle therapy without testosterone replacement (testosterone placebo) in obese (BMI e 30 kg/m2) older (age e 65 yrs) male Veterans. The investigators hypothesize that 1) lifestyle therapy + testosterone replacement will cause a greater improvement in physical function than lifestyle therapy without concomitant testosterone replacement; 2) lifestyle therapy + testosterone replacement will cause a greater preservation of fat-free mass and thigh muscle volume than lifestyle therapy without testosterone replacement, 3) lifestyle therapy + testosterone replacement will cause a greater preservation in BMD and bone quality than lifestyle therapy without testosterone replacement, and 4) lifestyle therapy + testosterone replacement will cause a greater reduction in intramuscular proinflammatory cytokines than lifestyle therapy without testosterone replacement. The overarching hypothesis across aims is that a multifactorial intervention by means of lifestyle therapy plus testosterone replacement will be the most effective approach for reversing sarcopenic obesity and frailty in obese older male adults, as mediated by their additive effects in suppressing chronic inflammation, and stimulating muscle and bone anabolism. Obesity in older adults, including many aging Veterans, is a major public health problem. In fact, the public health success that has occurred in recent years could be in danger if lifestyles of older adults are neglected. The novel health outcomes and mechanistic-based data generated from this proposed randomized clinical trial (RCT) will have important ramifications for the standard of care for this rapidly increasing segment of the aging Veteran population.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Testosterone plus Lifestyle Therapy | Active Comparator | Testosterone replacement in combination with behavioral diet to induce ~10% weight loss + supervised aerobic and exercise training |
|
| Placebo plus Lifestyle Therapy | Placebo Comparator | Placebo in combination with behavioral diet to induce ~10% weight loss and supervised aerobic and exercise training |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Testosterone | Drug | Daily testosterone gel applied once daily in the morning to intact skin |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in the Physical Performance Test | The primary functional outcome is the modified physical performance test, which includes seven standardized tasks (walking 50 ft, putting on and removing a coat, picking up a penny, standing up from a chair, lifting a book, climbing one flight of stairs, and performing a progressive Romberg tests) plus two additional tasks (climbing up and down four flights of stairs and performing a 360-degree turn). The score for each task ranges form 0 to 4; a perfect score is 36. Higher scores indicate better physical function. | Baseline and 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Endurance Capacity | Assessed by measuring peak oxygen consumption using indirect calorimetry during a treadmill exercise stress test | Baseline and 6 months |
| Change in Functional Status |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Total Testosterone Levels | as measured in the peripheral blood by liquid chromatography/mass spectrometry | Baseline and 6 months |
| Change in Estradiol | As measured by LC-MS/MS |
Inclusion Criteria:
Subjects will be
Exclusion Criteria:
Any major chronic diseases, or any condition that would interfere with exercise or dietary restriction, in which exercise or dietary restriction are contraindicated, or that would interfere with interpretation of results.
Examples include, but are not limited to:
Any contraindications to testosterone supplementation
Osteoporosis or a BMD T-score of -2.5 in the lumbar spine or total hip as well as those patients with a history of osteoporosis-related fracture (spine, hip, or wrist)
Male
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| Name | Affiliation | Role |
|---|---|---|
| Dennis T Villareal, MD | Michael E. DeBakey VA Medical Center, Houston, TX | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Michael E. DeBakey VA Medical Center, Houston, TX | Houston | Texas | 77030 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34375393 | Derived | Gregori G, Celli A, Barnouin Y, Paudyal A, Armamento-Villareal R, Napoli N, Qualls C, Villareal DT. Cognitive response to testosterone replacement added to intensive lifestyle intervention in older men with obesity and hypogonadism: prespecified secondary analyses of a randomized clinical trial. Am J Clin Nutr. 2021 Nov 8;114(5):1590-1599. doi: 10.1093/ajcn/nqab253. |
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Publications from this research will be made available to the public through the National Library of Medicine PubMed Central website within one year after the date of publication (guidance is provided on the ORD website).
MEDVAMC will not provide unrestricted, open public access to large scale health related datasets because of re-identification concerns and the obligation to protect Veterans' private information. However, controlled public access will be provided to the greatest extent possible under specific DUAs or other written agreements, and open access will be provided to the final datasets underlying peer-reviewed publications (aggregated data that can be released with privacy and confidentiality risks).
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After obtaining written informed consent, potential participants underwent a comprehensive medical screening procedure, including an exercise stress test. If they were found eligible based on the inclusion/exclusion criteria, they were randomized into one of the two treatment groups.
Participants were recruited through advertisements and review of medical records at the Michael E DeBakey VA Medical Center.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo + Lifestyle Therapy | Placebo in combination with behavioral diet to induce ~10% weight loss and supervised aerobic and exercise training Lifestyle Therapy: Weekly behavioral diet to induce ~10% weight loss in combination with supervised aerobic and exercise training three times a week Placebo: Placebo gel for testosterone |
| FG001 | Testosterone + Lifestyle Therapy | Testosterone replacement in combination with behavioral diet to induce ~10% weight loss + supervised aerobic and exercise training Testosterone: Daily testosterone gel applied once daily in the morning to intact skin Lifestyle Therapy: Weekly behavioral diet to induce ~10% weight loss in combination with supervised aerobic and exercise training three times a week |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo + Lifestyle Therapy | Placebo in combination with behavioral diet to induce ~10% weight loss and supervised aerobic and exercise training Lifestyle Therapy: Weekly behavioral diet to induce ~10% weight loss in combination with supervised aerobic and exercise training three times a week Placebo: Placebo gel for testosterone |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in the Physical Performance Test | The primary functional outcome is the modified physical performance test, which includes seven standardized tasks (walking 50 ft, putting on and removing a coat, picking up a penny, standing up from a chair, lifting a book, climbing one flight of stairs, and performing a progressive Romberg tests) plus two additional tasks (climbing up and down four flights of stairs and performing a 360-degree turn). The score for each task ranges form 0 to 4; a perfect score is 36. Higher scores indicate better physical function. | Posted | Mean | Standard Error | units on a scale | Baseline and 6 months |
|
6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo + Lifestyle Therapy | Placebo in combination with behavioral diet to induce ~10% weight loss and supervised aerobic and exercise training Lifestyle Therapy: Weekly behavioral diet to induce ~10% weight loss in combination with supervised aerobic and exercise training three times a week Placebo: Placebo gel for testosterone |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Congestive heart failure | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hypoglycemia, asymptomatic and symptomatic | Metabolism and nutrition disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dennis T Villareal, MD | Michael E DeBakey VA Medical Center | 713-794-7156 | dennis.villareal@va.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 11, 2020 | Jul 24, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D007006 | Hypogonadism |
| D000073496 | Frailty |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D013739 | Testosterone |
| ID | Term |
|---|---|
| D000737 | Androstenols |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 |
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| Lifestyle Therapy | Other | Weekly behavioral diet to induce ~10% weight loss in combination with supervised aerobic and exercise training three times a week |
|
| Placebo | Drug | Placebo gel for testosterone |
|
Assessed by the Functional Status Questionnaire. Score range: 0 to 36 with higher scores indicating better functional status
Provides information of the participants ability to perform activities of daily living.
| Baseline and 6 months |
| Change in Body Weight | Measured after an overnight fast using calibrated scales | Baseline and 6 months |
| Change in Lean Body Mass | Assessed by using dual-energy x-ray absorptiometry | Baseline and 6 months |
| Change in Fat Mass | Assessed by using dual-energy x-ray absorptiometry | Baseline and 6 months |
| Change in Thigh Muscle Volume | Assessed by using magnetic resonance imaging | Baseline and 6 months |
| Thigh Fat Volume | Volume of fat in the thigh by measured by magnetic resonance imaging | 6 months |
| Change in Total Hip Bone Mineral Density | Assessed by using dual-energy x-ray absorptiometry | Baseline and 6 months |
| Change in Lumbar Spine Bone Mineral Density | As measured by Dual energy x-ray absorptiometry | Baseline and 6 months |
| Change in Muscle Strength | assessed by total1-repetition maximum (the maximal weight lifted at one time; the totals are the sum of the maximal weights lifted in the biceps curl, bench press, 387 seated row, knee extension, knee flexion, and leg press exercises). | Baseline and 6 months |
| Change in Static Balance | assessed by one leg limb stance | Baseline and 6 months |
| Change in Dynamic Balance | Assessed by using the obstacle course | Baseline and 6 months |
| Change in Gait Speed | Determined by measuring the time needed to walk 25 ft. | Baseline and 6 months |
| Change in Composite Cognitive Z-score | Test of overall cognitive performance formed by averaging the standardized scores for several domains of cognitive function (attention, memory, executive, language, global). Higher scores indicate better cognitive status. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of the baseline scores (units on a scale). Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population | Baseline and 6 months |
| Change in Modified Mini-mental Exam | Test of global cognition with components for orientation, registration, attention, language, praxis, and immediate and delayed memory. Score ranges from 0 to 100 with higher scores indicate better cognition. | Baseline and 6 months |
| Stroop Interference | Assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute, well-known as the Stroop Effect. Minimum score is 0, there is no maximum value. Higher scores indicate better outcome. | Baseline and 6 months |
| Change in Word List Fluency | Measure of verbal production, semantic memory, and language. Minimum score is 0, there is no maximum value. Higher scores indicate better outcome. | Baseline and 6 months |
| Change in Ray Auditory Verbal Learning Test | The Rey Auditory Verbal Learning Test (RAVLT) evaluates a wide diversity of functions: short-term auditory-verbal memory, rate of learning, learning strategies, retroactive, and proactive interference, presence of confabulation of confusion in memory processes, retention of information. Minimum score is 0, there is no maximum value. Higher scores indicate better outcome. | Baseline and 6 months |
| Change in Trail A | Test of visuospatial scanning, speed of processing, mental flexibility, and executive function (with a greater focus on attention). Minimum score is 0, there is no maximum value. Higher scores indicate better outcome. | Baseline and 6 months |
| Change in Trail B | Test of visuospatial scanning, speed of processing, mental flexibility, and executive function (with a focus on executive function) Minimum score is 0, there is no maximum value. Higher scores indicate better outcome. | Baseline and 6 months |
| Change in Symbol Digital Modalities Test | Assesses key neurocognitive functions that underlie many substitution tasks, including attention, visual scanning, and motor speed. Minimum score is 0, there is no maximum value. Higher scores indicate better outcome. | Baseline and 6 months |
| Change in Trabecular Bone Score | The trabecular bone score is a measure of bone texture correlated with bone microarchitecture and a marker for the risk of osteoporosis. Minimum score is 0, there is no maximum value. Higher scores indicate better bone microarchitecture. | Baseline and 6 months |
| Change in C-terminal Telopeptide | biochemical marker of bone turnover (bone resorption) as measured by immunoassay technique | Baseline and 6 months |
| Change in N-terminal Propeptide of Type I Procollagen | Biochemical marker of bone turnover (bone formation) as measured by radioimmunoassay technique | Baseline and 6 months |
| Change in Insulin Growth Factor-1 | Measured by immunoassay methodology | Baseline and 6 months |
| Change in Trabecular Bone Score (Trabecular Bone Quality) | assessed by trabecular bone score (TBS), a newly developed index for assessing trabecular bone quality and fracture risk. TBS is a bone texture parameter that quantifies cancellous bone microachitecture, which is key in determining bone strength and resistance to fracture, by computing raw data from dual energy x-ray absorptiometry of the lumbar spine. There are no minimum or maximum values. Higher scores mean better outcome. | Baseline and 6 months |
| Change in Levels of 25-hydroxyvitamin D | assessed by using immunoassay methodology | Baseline and 6 months |
| Change in Parathyroid Hormone Level | Measured by immunoassay methodology as marker of bone metabolism | Baseline and 6 months |
| Change in High-sensitivity C-reactive Protein (Inflammatory Marker) | measured in the peripheral blood using immunoassay technique methodology | Baseline and 6 months |
| Change in Interleukin-6 | Measured from fasting serum using immunoassay technique as marker of inflammation | Baseline and 6 months |
| Baseline and 6 months |
| Change in Hematocrit | the ratio of the volume of red blood cells to the total volume of blood. | Baseline and 6 months |
| Change in Prostate Specific Antigen | blood test to screen for prostate cancer | Baseline and 6 months |
| Change in Short Form Health Survey (SF-36) Quality of Life Physical Component | Using Short Form-36 of Life Questionnaire Physical Component subscale. Minimum score is 0, Maximum score is 100. Higher scores indicate better outcome. | Baseline and 6 months |
| Change in International Prostate Symptom Score | Using the International Prostate Symptom Scoring (IPS); Minimum score is 0, Maximum score is 35. Higher scores mean worse outcome. | Baseline and 6 months |
| Change in Triglyceride Levels | Blood samples obtained in the fasting state as part of measurements of lipid profile | Baseline and 6 months |
| Change in HDL-cholesterol | Blood samples obtained in the fasting state as part of measurements of lipid profile | Baseline and 6 months |
| Change in Waist Circumference | Waist circumference as measured horizontally at the midpoint between the highest point of the iliac crest and the lowest portion of the 12th rib in the standing position. | Baseline and 6 months |
| Change in Glucose | Measured in the blood after overnight fast | Baseline and 6 months |
| Change in Mood | Using Yesavage Depression Scale Lower scores indicate better mood (range 0 to 30). | Baseline and 6 months |
| Number of Participants With Significant Changes in Functional Connectivity in the Default Mode Network | Functional connectivity was measured with seeds of the DMN (medial prefrontal cortex [MPFC] and posterior cingulate cortex [PCC]). Correlation coefficients representing the degree of connectivity between hypothesized regions were Fisher transformed. An a priori threshold of p<.001 at the voxel level and p<.05, FDR corrected for multiple comparisons across the whole brain, at the cluster level were used to determine significant connectivity. | Baseline and 6 months |
| Change in Skeletal Muscle Growth Factor (MYOD1) | Assessed by using RNA-seq quantification of gene expression in skeletal muscles obtained during muscle biopsies. | Baseline and 6 months |
| Change in Peripheral Quantitative Computed Tomography Measures (Volumetric Bone Density) | assessed by quantitative computed tomography at 4% distal tibia using the following thresholds: 180 mg/cm3 and 45% of the area | Baseline and 6 months |
| BG001 |
| Testosterone + Lifestyle Therapy |
Testosterone replacement in combination with behavioral diet to induce ~10% weight loss + supervised aerobic and exercise training Testosterone: Daily testosterone gel applied once daily in the morning to intact skin Lifestyle Therapy: Weekly behavioral diet to induce ~10% weight loss in combination with supervised aerobic and exercise training three times a week |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Ethnicity was reported by the participants | Count of Participants | Participants |
|
| Race (NIH/OMB) | Race was reported by the participants | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body mass index | The body-mass index is the weight in kilograms divided by the square of the height in meters | Mean | Standard Deviation | kg/m^2 |
|
| Total testosterone level | Measured in the blood during early am in the fasting state. | Mean | Standard Deviation | ng/dl |
|
| Physical Performance Test score | The test includes walking 50 ft, putting on and removing a coat, picking up a penny, standing from a chair, lifting a book, climbing a flight of stairs, climbing up and down 4 flight of stairs, and performing a 360-degree turn. The score for each task ranges from 0 to 4; a perfect score is 36. Higher scores indicate better physical function. | Mean | Standard Deviation | units on a scale |
|
| OG001 | Testosterone + Lifestyle Therapy | Testosterone replacement in combination with behavioral diet to induce ~10% weight loss + supervised aerobic and exercise training Testosterone: Daily testosterone gel applied once daily in the morning to intact skin Lifestyle Therapy: Weekly behavioral diet to induce ~10% weight loss in combination with supervised aerobic and exercise training three times a week |
|
|
|
| Secondary | Change in Endurance Capacity | Assessed by measuring peak oxygen consumption using indirect calorimetry during a treadmill exercise stress test | Posted | Mean | Standard Error | ml/kg/min | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Functional Status | Assessed by the Functional Status Questionnaire. Score range: 0 to 36 with higher scores indicating better functional status Provides information of the participants ability to perform activities of daily living. | Posted | Mean | Standard Error | units on a scale | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Body Weight | Measured after an overnight fast using calibrated scales | Posted | Mean | Standard Error | kilograms | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Lean Body Mass | Assessed by using dual-energy x-ray absorptiometry | Posted | Mean | Standard Error | kg | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Fat Mass | Assessed by using dual-energy x-ray absorptiometry | Posted | Mean | Standard Error | kg | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Thigh Muscle Volume | Assessed by using magnetic resonance imaging | Posted | Mean | Standard Error | cm^3 | Baseline and 6 months |
|
|
|
|
| Secondary | Thigh Fat Volume | Volume of fat in the thigh by measured by magnetic resonance imaging | Posted | Mean | Standard Error | cm^3 | 6 months |
|
|
|
|
| Secondary | Change in Total Hip Bone Mineral Density | Assessed by using dual-energy x-ray absorptiometry | Posted | Mean | Standard Error | gm/cm^2 | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Lumbar Spine Bone Mineral Density | As measured by Dual energy x-ray absorptiometry | Posted | Mean | Standard Error | gm/cm^2 | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Muscle Strength | assessed by total1-repetition maximum (the maximal weight lifted at one time; the totals are the sum of the maximal weights lifted in the biceps curl, bench press, 387 seated row, knee extension, knee flexion, and leg press exercises). | Posted | Mean | Standard Error | kg | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Static Balance | assessed by one leg limb stance | Posted | Mean | Standard Error | seconds | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Dynamic Balance | Assessed by using the obstacle course | Posted | Mean | Standard Error | seconds | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Gait Speed | Determined by measuring the time needed to walk 25 ft. | Posted | Mean | Standard Error | m/min | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Composite Cognitive Z-score | Test of overall cognitive performance formed by averaging the standardized scores for several domains of cognitive function (attention, memory, executive, language, global). Higher scores indicate better cognitive status. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of the baseline scores (units on a scale). Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population | Posted | Mean | Standard Error | z-score | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Modified Mini-mental Exam | Test of global cognition with components for orientation, registration, attention, language, praxis, and immediate and delayed memory. Score ranges from 0 to 100 with higher scores indicate better cognition. | Posted | Mean | Standard Error | units on a scale | Baseline and 6 months |
|
|
|
|
| Secondary | Stroop Interference | Assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute, well-known as the Stroop Effect. Minimum score is 0, there is no maximum value. Higher scores indicate better outcome. | Posted | Mean | Standard Error | score on a scale | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Word List Fluency | Measure of verbal production, semantic memory, and language. Minimum score is 0, there is no maximum value. Higher scores indicate better outcome. | Posted | Mean | Standard Error | units on a scale | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Ray Auditory Verbal Learning Test | The Rey Auditory Verbal Learning Test (RAVLT) evaluates a wide diversity of functions: short-term auditory-verbal memory, rate of learning, learning strategies, retroactive, and proactive interference, presence of confabulation of confusion in memory processes, retention of information. Minimum score is 0, there is no maximum value. Higher scores indicate better outcome. | Posted | Mean | Standard Error | units on a scale | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Trail A | Test of visuospatial scanning, speed of processing, mental flexibility, and executive function (with a greater focus on attention). Minimum score is 0, there is no maximum value. Higher scores indicate better outcome. | Posted | Mean | Standard Error | units on a scale | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Trail B | Test of visuospatial scanning, speed of processing, mental flexibility, and executive function (with a focus on executive function) Minimum score is 0, there is no maximum value. Higher scores indicate better outcome. | Posted | Mean | Standard Error | units on a scale | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Symbol Digital Modalities Test | Assesses key neurocognitive functions that underlie many substitution tasks, including attention, visual scanning, and motor speed. Minimum score is 0, there is no maximum value. Higher scores indicate better outcome. | Posted | Mean | Standard Error | units on a scale | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Trabecular Bone Score | The trabecular bone score is a measure of bone texture correlated with bone microarchitecture and a marker for the risk of osteoporosis. Minimum score is 0, there is no maximum value. Higher scores indicate better bone microarchitecture. | Posted | Mean | Standard Error | units on a scale | Baseline and 6 months |
|
|
|
|
| Secondary | Change in C-terminal Telopeptide | biochemical marker of bone turnover (bone resorption) as measured by immunoassay technique | Posted | Mean | Standard Error | µg/L | Baseline and 6 months |
|
|
|
|
| Secondary | Change in N-terminal Propeptide of Type I Procollagen | Biochemical marker of bone turnover (bone formation) as measured by radioimmunoassay technique | Posted | Mean | Standard Error | µg/L | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Insulin Growth Factor-1 | Measured by immunoassay methodology | Posted | Mean | Standard Error | ng/mL | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Trabecular Bone Score (Trabecular Bone Quality) | assessed by trabecular bone score (TBS), a newly developed index for assessing trabecular bone quality and fracture risk. TBS is a bone texture parameter that quantifies cancellous bone microachitecture, which is key in determining bone strength and resistance to fracture, by computing raw data from dual energy x-ray absorptiometry of the lumbar spine. There are no minimum or maximum values. Higher scores mean better outcome. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Levels of 25-hydroxyvitamin D | assessed by using immunoassay methodology | Posted | Mean | Standard Error | ng/mL | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Parathyroid Hormone Level | Measured by immunoassay methodology as marker of bone metabolism | Posted | Mean | Standard Error | pg/mL | Baseline and 6 months |
|
|
|
|
| Secondary | Change in High-sensitivity C-reactive Protein (Inflammatory Marker) | measured in the peripheral blood using immunoassay technique methodology | Posted | Mean | Standard Error | mg/dl | Baseline and 6 months |
|
|
|
|
| Secondary | Change in Interleukin-6 | Measured from fasting serum using immunoassay technique as marker of inflammation | Posted | Mean | Standard Error | pg/mL | Baseline and 6 months |
|
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|
|
| Other Pre-specified | Change in Total Testosterone Levels | as measured in the peripheral blood by liquid chromatography/mass spectrometry | Posted | Mean | Standard Error | ng/dL | Baseline and 6 months |
|
|
|
|
| Other Pre-specified | Change in Estradiol | As measured by LC-MS/MS | Posted | Mean | Standard Error | pg/dL | Baseline and 6 months |
|
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|
|
| Other Pre-specified | Change in Hematocrit | the ratio of the volume of red blood cells to the total volume of blood. | Posted | Mean | Standard Error | percentage of red blood cells | Baseline and 6 months |
|
|
|
|
| Other Pre-specified | Change in Prostate Specific Antigen | blood test to screen for prostate cancer | Posted | Mean | Standard Error | ng/mL | Baseline and 6 months |
|
|
|
|
| Other Pre-specified | Change in Short Form Health Survey (SF-36) Quality of Life Physical Component | Using Short Form-36 of Life Questionnaire Physical Component subscale. Minimum score is 0, Maximum score is 100. Higher scores indicate better outcome. | Posted | Mean | Standard Error | units on a scale | Baseline and 6 months |
|
|
|
|
| Other Pre-specified | Change in International Prostate Symptom Score | Using the International Prostate Symptom Scoring (IPS); Minimum score is 0, Maximum score is 35. Higher scores mean worse outcome. | Posted | Mean | Standard Error | units on a scale | Baseline and 6 months |
|
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| Other Pre-specified | Change in Triglyceride Levels | Blood samples obtained in the fasting state as part of measurements of lipid profile | Posted | Mean | Standard Error | mg/dl | Baseline and 6 months |
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| Other Pre-specified | Change in HDL-cholesterol | Blood samples obtained in the fasting state as part of measurements of lipid profile | Posted | Mean | Standard Error | mg/dl | Baseline and 6 months |
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| Other Pre-specified | Change in Waist Circumference | Waist circumference as measured horizontally at the midpoint between the highest point of the iliac crest and the lowest portion of the 12th rib in the standing position. | Posted | Mean | Standard Error | cm | Baseline and 6 months |
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| Other Pre-specified | Change in Glucose | Measured in the blood after overnight fast | Posted | Mean | Standard Error | mg/dl | Baseline and 6 months |
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| Other Pre-specified | Change in Mood | Using Yesavage Depression Scale Lower scores indicate better mood (range 0 to 30). | Posted | Mean | Standard Error | score on a scale | Baseline and 6 months |
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| Other Pre-specified | Number of Participants With Significant Changes in Functional Connectivity in the Default Mode Network | Functional connectivity was measured with seeds of the DMN (medial prefrontal cortex [MPFC] and posterior cingulate cortex [PCC]). Correlation coefficients representing the degree of connectivity between hypothesized regions were Fisher transformed. An a priori threshold of p<.001 at the voxel level and p<.05, FDR corrected for multiple comparisons across the whole brain, at the cluster level were used to determine significant connectivity. | The number of subjects per group is less than the overall number of subjects enrolled in the trial because this was an add-on outcome later in the study. Moreover, the analyses are limited to subjects with complete evaluable pre and post-MRI data. | Posted | Count of Participants | Participants | Baseline and 6 months |
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| Other Pre-specified | Change in Skeletal Muscle Growth Factor (MYOD1) | Assessed by using RNA-seq quantification of gene expression in skeletal muscles obtained during muscle biopsies. | Posted | Mean | Standard Error | log2fold | Baseline and 6 months |
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| Other Pre-specified | Change in Peripheral Quantitative Computed Tomography Measures (Volumetric Bone Density) | assessed by quantitative computed tomography at 4% distal tibia using the following thresholds: 180 mg/cm3 and 45% of the area | Posted | Mean | Standard Error | mg/cm^3 | Baseline and 6 months |
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| 0 |
| 41 |
| 1 |
| 41 |
| 12 |
| 41 |
| EG001 | Testosterone + Lifestyle Therapy | Testosterone replacement in combination with behavioral diet to induce ~10% weight loss + supervised aerobic and exercise training Testosterone: Daily testosterone gel applied once daily in the morning to intact skin Lifestyle Therapy: Weekly behavioral diet to induce ~10% weight loss in combination with supervised aerobic and exercise training three times a week | 0 | 42 | 1 | 42 | 6 | 42 |
| Cardiac arrest | Cardiac disorders | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Bleeding peptic ulcer | Gastrointestinal disorders | Systematic Assessment |
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| Duodenitis | Gastrointestinal disorders | Systematic Assessment |
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| Cellulitis | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
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| Ankle fracture | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Idiopathic thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Hyperosmolar hyperglycemic state | Endocrine disorders | Systematic Assessment |
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| Intestinal obstruction | Gastrointestinal disorders | Systematic Assessment |
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| Elevated PSA | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Dizziness/orthostasis | Vascular disorders | Systematic Assessment |
|
Not provided
Not provided
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D010335 | Pathologic Processes |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045165 | Testosterone Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
6 months vs Baseline
| t-test, 2 sided |
| .02 |
Using DESeq2 R package. P values were adjusted using the Benjamini and Hochberg's approach for controlling the false discovery rate |
| Mean Difference (Net) |
| 0.58 |
| Standard Error of the Mean |
| 0.12 |
| 2-Sided |
| Superiority |
Final vs baseline
| 0.3 |
| Mean Difference (Net) |
| -0.3 |
| Standard Error of the Mean |
| 1.3 |
| 2-Sided |
| Superiority |