Testosterone Replacement to Augment Lifestyle Therapy in Obese Older Veterans

睾酮替代疗法可增强肥胖老年退伍军人的生活方式治疗

基本信息

批准号：
8970692
负责人：
DENNIS T. VILLAREAL
金额：
--
依托单位：
MICHAEL E DEBAKEY VA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2019-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8970692
关键词：
Admission activity Adult Affect Age Aging American Anabolism Biological Preservation Body Weight decreased Bone Density Bone Resorption Chronic Chronic Care Clinical Data Diet Double-Blind Method Elderly Eligibility Determination Equilibrium Exercise Failure Fatty acid glycerol esters Frail Elderly Future Gene Expression General Population Geometry Goals Growth Factor Guidelines Health Health Care Costs Healthcare Systems Hip region structure Hormones Hyperphagia Impairment Inflammation Insulin-Like Growth Factor I Interleukin-6 Intervention Intramuscular Life Style Lifestyle Therapy Magnetic Resonance Imaging Mediating Medical Methods Morbidity - disease rate Muscle Nursing Homes Obesity Older Population Osteogenesis Osteopenia Outcome Overweight Patients Performance Physical Function Physical Performance Placebo Control Placebos Population Prevalence Protein Isoforms Public Health Quality of life Randomized Reverse Transcriptase Polymerase Chain Reaction Serum Skeletal Muscle Suggestion TNF gene Testing Testosterone Thigh structure Tissue Sample Veterans Weight Western Blotting X-Ray Computed Tomography age related age-related muscle loss base bone bone mass bone quality comparative efficacy cytokine efficacy trial exercise training frailty functional outcomes functional status health care service hormone deficiency improved lean body mass lifestyle intervention male mortality multi-component intervention muscle form muscle strength neglect novel obesity treatment older men older patient performance tests prevent programs protein expression public health relevance reduced muscle mass restoration sarcopenia sarcopenic obesity sedentary lifestyle standard care standard of care success testosterone replacement therapy treatment group

项目摘要

DESCRIPTION (provided by applicant): 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, our 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. We 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. Our 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 RCT will have important ramifications for the standard of care for this rapidly increasing segment of the aging veteran population.

描述（由申请人提供）：肥胖不仅在美国人中很普遍，而且在使用VA医疗设施的退伍军人中，肥胖症甚至更为普遍。未能协助退伍军人管理体重和久坐的生活方式会影响当前的治疗，并增加对VA卫生保健服务的未来需求。随着衰老而减少肌肉质量，由于肥胖而需要携带额外质量的需求使肥胖的老年退伍军人独立起作用，并导致脆弱，导致疗养院的入院增加，发病率和死亡率提高。初步研究的数据表明，导致这种研究的人群体重减轻的生活方式疗法可改善身体机能并改善脆弱性。但是，这种身体功能的改善充其量是适度的，大多数肥胖的老年人仍然身体虚弱。更重要的是，人们担心生活方式疗法可能会加剧肌肉减少症和骨质减少症的基础，并因减肥诱导的瘦体重和骨矿物质密度（BMD）的损失而加剧。结果，大多数老年医生不愿推荐生活方式疗法，其中包括肥胖老年患者体重减轻的生活方式疗法，尽管建议减肥和运动的组合作为肥胖患者的标准护理的一部分。因此，毫不奇怪的是，在退伍军人中，如果有符合条件的退伍军人为70岁或以上，则举动（管理超重/肥胖的退伍军人）计划将没有任何准则。除了暴饮暴食和缺乏运动外，合成代谢激素（即睾丸激素）与年龄相关的下降可能会导致肌肉减少症和骨质减少症，这又会因肥胖而加剧。确实，我们的初步研究发现，肥胖的老年男性在基线时的血清睾丸激素水平显着较低，在整个生活方式疗法期间，这仍然很低。由于已证明睾丸激素替代疗法可以增加肌肉质量和BMD，因此在肥胖老年人的生活方式疗法期间伴随睾丸激素替代可能会保留瘦体重和BMD，以及反向脆弱。因此，解决肌肉减少肥胖和脆弱问题的最佳管理可能需要全面的生活方式干预和合成代谢激素缺乏症的方法。 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年轻的退伍军人。我们假设1）生活方式疗法 +睾丸激素的替代将比生活方式疗法而没有睾丸激素的替代，将导致身体机能的改善； 2）生活方式疗法 +睾丸激素的替代将导致与没有睾丸激素替代的生活方式治疗相比，无脂肪的质量和大腿肌肉量更大细胞因子比没有睾丸激素替代的生活方式疗法。我们各个目标的总体假设是，通过生活方式疗法以及睾丸激素替代的多因素干预措施将是肥胖年龄较大的男性成年人逆转肌肉减少肥胖和脆弱的最有效方法，这些方法是由它们的累加效应介导的，它是在抑制慢性炎症以及刺激肌肉和骨骼的骨骼和骨骼动力学方面介导的。包括许多老年退伍军人在内的老年人的肥胖是一个主要的公共卫生问题。实际上，如果忽略老年人的生活方式，近年来发生的公共卫生成功可能会处于危险之中。这项提出的RCT产生的新型健康结果和基于机械的数据将对这一迅速增长的老年退伍军人人群的迅速增加，对护理标准产生重要的影响。