Obesity and Hypogonadism Clinical Trial
— LITROSOfficial title:
Testosterone Replacement to Augment Lifestyle Therapy in Obese Older Veterans
| Verified date | January 2022 |
| Source | VA Office of Research and Development |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 83 |
| Est. completion date | December 31, 2019 |
| Est. primary completion date | July 31, 2019 |
| Accepts healthy volunteers | No |
| Gender | Male |
| Age group | 65 Years to 85 Years |
| Eligibility | Inclusion Criteria: Subjects will be - older (65-85 yr) - obese (BMI 30 kg/m2 or greater) Veteran men with low testosterone (less than 300 mg/dL) as defined by the Endocrine Society - mild to moderately frail - must have stable weight (~not less than or more than 2 kg) during the last 6 months - sedentary (regular exercise less than 1 h/week or less than 2x/week for the last 6 months) 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: - cardiopulmonary disease (e.g. recent myocardial infarction (MI), unstable angina, stroke etc) or unstable disease (e.g. CHF) - severe orthopedic/musculoskeletal or neuromuscular impairments - visual or hearing impairments - cognitive impairment (Mini Mental State Exam Score less than 24) - current use of bone active drugs - uncontrolled diabetes (i.e. fasting blood glucose more than 140 mg/dl and/or HbA1c greater than 9.5%). - Any contraindications to testosterone supplementation - history of prostate or breast cancer - history of testicular disease - untreated sleep apnea - hematocrit more than 50% - prostate-related findings of palpable nodule on exam, a serum PSA of 4.0 ng/ml or greater - International Prostate Symptom Sore more than 19 - history of venous thromboembolism - 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) |
| Country | Name | City | State |
|---|---|---|---|
| United States | Michael E. DeBakey VA Medical Center, Houston, TX | Houston | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| VA Office of Research and Development | Baylor College of Medicine, Biomedical Research Institute of New Mexico, Michael E. DeBakey VA Medical Center |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Change in Total Testosterone Levels | as measured in the peripheral blood by liquid chromatography/mass spectrometry | Baseline and 6 months | |
| Other | Change in Estradiol | As measured by LC-MS/MS | Baseline and 6 months | |
| Other | Change in Hematocrit | the ratio of the volume of red blood cells to the total volume of blood. | Baseline and 6 months | |
| Other | Change in Prostate Specific Antigen | blood test to screen for prostate cancer | Baseline and 6 months | |
| Other | 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 | |
| Other | 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 | |
| Other | Change in Triglyceride Levels | Blood samples obtained in the fasting state as part of measurements of lipid profile | Baseline and 6 months | |
| Other | Change in HDL-cholesterol | Blood samples obtained in the fasting state as part of measurements of lipid profile | Baseline and 6 months | |
| Other | 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 | |
| Other | Change in Glucose | Measured in the blood after overnight fast | Baseline and 6 months | |
| Other | Change in Mood | Using Yesavage Depression Scale Lower scores indicate better mood (range 0 to 30). | Baseline and 6 months | |
| Other | 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 | |
| Other | 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 | |
| Other | 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 | |
| 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. | Baseline and 6 months | |
| Secondary | Change in Endurance Capacity | Assessed by measuring peak oxygen consumption using indirect calorimetry during a treadmill exercise stress test | 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. |
Baseline and 6 months | |
| Secondary | Change in Body Weight | Measured after an overnight fast using calibrated scales | Baseline and 6 months | |
| Secondary | Change in Lean Body Mass | Assessed by using dual-energy x-ray absorptiometry | Baseline and 6 months | |
| Secondary | Change in Fat Mass | Assessed by using dual-energy x-ray absorptiometry | Baseline and 6 months | |
| Secondary | Change in Thigh Muscle Volume | Assessed by using magnetic resonance imaging | Baseline and 6 months | |
| Secondary | Thigh Fat Volume | Volume of fat in the thigh by measured by magnetic resonance imaging | 6 months | |
| Secondary | Change in Total Hip Bone Mineral Density | Assessed by using dual-energy x-ray absorptiometry | Baseline and 6 months | |
| Secondary | Change in Lumbar Spine Bone Mineral Density | As measured by Dual energy x-ray absorptiometry | 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). | Baseline and 6 months | |
| Secondary | Change in Static Balance | assessed by one leg limb stance | Baseline and 6 months | |
| Secondary | Change in Dynamic Balance | Assessed by using the obstacle course | Baseline and 6 months | |
| Secondary | Change in Gait Speed | Determined by measuring the time needed to walk 25 ft. | 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 |
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. | 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. |
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. | 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. |
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. |
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. |
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. |
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. |
Baseline and 6 months | |
| Secondary | Change in C-terminal Telopeptide | biochemical marker of bone turnover (bone resorption) as measured by immunoassay technique | 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 | Baseline and 6 months | |
| Secondary | Change in Insulin Growth Factor-1 | Measured by immunoassay methodology | 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. |
Baseline and 6 months | |
| Secondary | Change in Levels of 25-hydroxyvitamin D | assessed by using immunoassay methodology | Baseline and 6 months | |
| Secondary | Change in Parathyroid Hormone Level | Measured by immunoassay methodology as marker of bone metabolism | Baseline and 6 months | |
| Secondary | Change in High-sensitivity C-reactive Protein (Inflammatory Marker) | measured in the peripheral blood using immunoassay technique methodology | Baseline and 6 months | |
| Secondary | Change in Interleukin-6 | Measured from fasting serum using immunoassay technique as marker of inflammation | Baseline and 6 months |