Testosterone Replacement to Augment Lifestyle Therapy in Obese Older Veterans
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 1
- 主要终点
- Change in the Physical Performance Test
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 85 Years（Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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)
研究组 & 干预措施
Testosterone plus Lifestyle Therapy
Testosterone replacement in combination with behavioral diet to induce ~10% weight loss + supervised aerobic and exercise training
干预措施: Testosterone (Drug)
Testosterone plus Lifestyle Therapy
Testosterone replacement in combination with behavioral diet to induce ~10% weight loss + supervised aerobic and exercise training
干预措施: Lifestyle Therapy (Other)
Placebo plus Lifestyle Therapy
Placebo in combination with behavioral diet to induce ~10% weight loss and supervised aerobic and exercise training
干预措施: Lifestyle Therapy (Other)
Placebo plus Lifestyle Therapy
Placebo in combination with behavioral diet to induce ~10% weight loss and supervised aerobic and exercise training
干预措施: Placebo (Drug)
结局指标
主要结局
Change in the Physical Performance Test
时间窗: Baseline and 6 months
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.
次要结局
- Change in Endurance Capacity(Baseline and 6 months)
- Change in Functional Status(Baseline and 6 months)
- Change in Body Weight(Baseline and 6 months)
- Change in Lean Body Mass(Baseline and 6 months)
- Change in Fat Mass(Baseline and 6 months)
- Change in Thigh Muscle Volume(Baseline and 6 months)
- Thigh Fat Volume(6 months)
- Change in Total Hip Bone Mineral Density(Baseline and 6 months)
- Change in Lumbar Spine Bone Mineral Density(Baseline and 6 months)
- Change in Muscle Strength(Baseline and 6 months)
- Change in Static Balance(Baseline and 6 months)
- Change in Dynamic Balance(Baseline and 6 months)
- Change in Gait Speed(Baseline and 6 months)
- Change in Composite Cognitive Z-score(Baseline and 6 months)
- Change in Modified Mini-mental Exam(Baseline and 6 months)
- Stroop Interference(Baseline and 6 months)
- Change in Word List Fluency(Baseline and 6 months)
- Change in Ray Auditory Verbal Learning Test(Baseline and 6 months)
- Change in Trail A(Baseline and 6 months)
- Change in Trail B(Baseline and 6 months)
- Change in Symbol Digital Modalities Test(Baseline and 6 months)
- Change in Trabecular Bone Score(Baseline and 6 months)
- Change in C-terminal Telopeptide(Baseline and 6 months)
- Change in N-terminal Propeptide of Type I Procollagen(Baseline and 6 months)
- Change in Insulin Growth Factor-1(Baseline and 6 months)
- Change in Trabecular Bone Score (Trabecular Bone Quality)(Baseline and 6 months)
- Change in Levels of 25-hydroxyvitamin D(Baseline and 6 months)
- Change in Parathyroid Hormone Level(Baseline and 6 months)
- Change in High-sensitivity C-reactive Protein (Inflammatory Marker)(Baseline and 6 months)
- Change in Interleukin-6(Baseline and 6 months)