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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：
8794262
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 2017-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8794262
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 Databases Diet Double-Blind Method Dual-Energy X-Ray Absorptiometry Elderly Equilibrium Exercise Failure Fatty acid glycerol esters Frail Elderly Future Gene Expression General Population Geometry Goals Growth Factor Guidelines Health Health Services Healthcare Healthcare Systems Hip region structure Hormones Hyperphagia 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 Osteogenesis Osteopenia Outcome Overweight Patients Performance Physical Function Placebo Control Placebos Population Prevalence Protein Isoforms Public Health Quality of life Randomized Reverse Transcriptase Polymerase Chain Reaction Serum Skeletal Muscle TNF gene Testing Testosterone Thigh structure Tissue Sample Training Veterans Weight Western Blotting X-Ray Computed Tomography age related base bone bone mass bone quality comparative efficacy cytokine efficacy trial frailty functional outcomes functional status 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 restoration sarcopenia sedentary lifestyle standard care standard of care success testosterone replacement therapy

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）：