Lifestyle Intervention and Testosterone Replacement in Obese Seniors
关键词
抽象
描述
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.
日期
最后验证: | 12/31/2019 |
首次提交: | 01/20/2015 |
提交的预估入学人数: | 02/17/2015 |
首次发布: | 02/19/2015 |
上次提交的更新: | 01/12/2020 |
最近更新发布: | 01/13/2020 |
实际学习开始日期: | 01/31/2015 |
预计主要完成日期: | 07/30/2019 |
预计完成日期: | 12/30/2019 |
状况或疾病
干预/治疗
Drug: Testosterone + Lifestyle Therapy
Other: Lifestyle Therapy
Drug: Placebo + Lifestyle Therapy
相
手臂组
臂 | 干预/治疗 |
---|---|
Active Comparator: Testosterone + Lifestyle Therapy Testosterone replacement in combination with behavioral diet to induce ~10% weight loss + supervised aerobic and exercise training | Drug: Testosterone + Lifestyle Therapy Daily testosterone gel applied once daily in the morning to intact skin |
Placebo Comparator: Placebo + Lifestyle Therapy Placebo in combination with behavioral diet to induce ~10% weight loss and supervised aerobic and exercise training | Drug: Placebo + Lifestyle Therapy Placebo gel for testosterone |
资格标准
有资格学习的年龄 | 65 Years 至 65 Years |
有资格学习的性别 | Male |
接受健康志愿者 | 是 |
标准 | 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 8 - Osteoporosis or a BMD T-score of -2.5 in the lumbar spine - total hip - as well as those patients with a history of osteoporosis-related fracture (spine, hip, or wrist) |
结果
主要结果指标
1. Objective physical performance test [6 month]
次要成果指标
1. Fat free mass [6 months]
2. Fat mass [6 months]
3. Visceral Fat and thigh muscle mass [6 months]
4. Total Hip Bone Mineral Density [6 months]
5. Biochemical Markers of Bone Turnover [3 and 6 months]
6. Volumetric BMD [6 months]
7. Skeletal Muscle Cytokines, Mitochondrial Fxn, and Growth Factors [6 months]
8. Mood [6 months]
9. Quality of Life [6 months]
10. Serum biochemistries [3 and 6 months]
11. Prostate Symptom Assessment [3 and 6 months]
12. Change in strength [Baseline and 6 months]
13. Change in balance [Baseline and 6 months]
14. Change in Functional Status [Baseline and 6 months]
15. Change in endurance capacity [Baseline and 6 months]
16. Change in gait [Baseline and 6 months]
17. Change in trabecular bone score [Baseline and 6 months]
18. Change in hip structure [Baseline and 6 months]
19. Change in bone quality [Baseline and 6 months]
20. Change in body weight [Baseline and 6 months]
21. Change in testosterone levels [Baseline and 6 months]
22. Change in sex hormone globulin [Baseline and 6 months]
23. Change in metabolic hormones [Baseline and 6 months]
24. thigh muscle mass [Baseline and 6 months]
25. composite cognitive z-score [Baseline and 6 months]
26. modified mini-mental exam [Baseline and 6 months]
27. stroop color naming [Baseline and 6 months]
28. word list fluency [Baseline and 6 months]
29. ray auditory verbal learning test [Baseline and 6 months]
30. Trail A/B [Baseline and 6 months]
31. Change in skeletal muscle growth factors [Baseline and 6 months]
32. Change in waist circumference [Baseline and 6 months]
33. Change in lumbar spine bone mineral density [Baseline and 6 months]
34. Change in bone metabolism [Baseline and six months]
35. Change in lipid profile [Baseline and 6 months]
36. Change in peripheral quantitative computed tomography [Baseline and six months]
37. Change in Blood pressure [Baseline and 6 months]
38. Change in procollagen propeptide [Baseline and 6 months]
39. Change in metabolic syndrome [Baseline and 6 months]
40. change in inflammatory markers [baseline and 6 months]
其他成果措施
1. Change in BRAIN MRI including functional connectivity [Baseline and 6 months]