Combining Testosterone Therapy and Exercise to Improve Function Post Hip Fracture

结合睾酮治疗和运动来改善髋部骨折后的功能

• 批准号: 9591560
• 负责人: ELLEN F BINDER
• 金额: $ 2.14万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9591560
• 关键词: Activities of Daily Living; Adherence; Adverse event; Age; Androgens; Award; Biochemical; Blinded; Bone Density; Caring; Clinical; Clinical Trials Cooperative Group; Contralateral; Double-Blind Method; Dual-Energy X-Ray Absorptiometry; Elderly; Enrollment; Event; Exercise; Failure; Female; Femur; Fracture; Frail Elderly; Gait speed; Goals; Grant; Health Care Costs; Hip Fractures; Hip region structure; Impairment; Individual; Intervention; Leg; Limb structure; Manuals; Measurement; Measures; Mission; Monitor; Morbidity - disease rate; Outcome Measure; Patient Self-Report; Patients; Performance; Pharmaceutical Preparations; Phase; Physical Function; Physical Performance; Pilot Projects; Placebos; Population; Procedures; Protocols documentation; Public Health; Quality of life; Questionnaires; Randomized; Reporting; Risk Factors; SF-36; Serum; Site; Skeletal Muscle; Supervision; Supplementation; Testing; Testosterone; Walking; Woman; active method; clinical research site; design; exercise training; frailty; functional decline; functional disability; functional status; human old age (65+); improved; improved functioning; lean body mass; mortality; multidisciplinary; muscle form; muscle strength; older women; patient population; performance tests; post intervention; primary outcome; recruit; screening; secondary outcome; virtual

Hip fractures are common among older women and can have a devastating impact on their ability to remain independent. A clinically important functional decline and failure to recover following a hip fracture has been documented as much as a year after the fracture, even among individuals who were functioning at high levels before the event. Age-associated androgen deficiency in women contributes to deficits in muscle mass, strength and power that are common in this patient population before the fracture, and are exacerbated afterward. A pilot study of testosterone (T) supplementation in elderly female hip fracture patients has demonstrated the feasibility of T treatment in this population, and showed gains in lean body mass (LBM) and muscle strength with active drug, compared to placebo. The benefits of exercise in restoring muscle strength and physical function after a hip fracture have been documented. However, it remains unclear whether T treatment can augment the effects of exercise on mobility and patient-reported function, or whether any observed benefits are sustained beyond the period of active treatment. Proposed is a 3-group, multi-center, randomized, placebo-controlled, double-blinded, parallel group clinical trial in frail elderly female hip fracture patients. 300 female hip fracture patients will be enrolled from 6 clinical sites, using objective screening criteria for T deficiency (serum total testosterone level < 30 ng/dl) and physical frailty (Modified Physical Performance Test (PPT) Score < 28). The trial will compare the effects of supervised exercise training (EX) alone, EX combined with T therapy (EX+T) and no EX with placebo T treatment (CON), to ascertain the incremental impact of adding T to ET in older adult women following hip fracture. The 6-month intervention will be followed by a 6-month no-treatment sustainability phase. The primary outcome measure is the Six Minute Walk Distance (6MWD). Secondary outcome measures include: 1) dual energy x-ray absorptiometry (DXA) measurements of whole body and appendicular LBM and bone mineral density of the unfractured proximal femur; 2) maximal skeletal muscle strength (1-RM) for leg extension in both limbs; 3) objective physical performance measures; and 4) self-reported performance of activities of daily living and quality of life, including the Hip Rating Questionnaire (HRQ). We plan to carefully monitor testosterone levels, adverse events, biochemical parameters, and factors related to adherence to the interventions. Information from this study has the potential to alter treatment of hip fracture in older women, a problem that contributes to significant morbidity and mortality, and has a large public health impact. The proposed study is highly aligned with NIA’s mission of identifying interventions that target common geriatric conditions, and improve treatment options for older adults with multiple morbidities or risk factors.

髋部骨折在老年妇女中很常见，可能对她们的能力产生毁灭性的影响， 保持独立。临床上重要的功能下降和髋部骨折后无法恢复， 在骨折后一年多的时间里，即使是在高功能的人中， 事件发生前的水平。女性中与睾酮相关的雄激素缺乏导致肌肉质量不足， 在骨折前，这种患者人群中常见的力量和力量， 之后。一项在老年女性髋部骨折患者中补充睾酮（T）的初步研究， 证明了T治疗在该人群中的可行性，并显示瘦体重（LBM）和 与安慰剂相比，活性药物的肌肉强度。运动对恢复肌肉力量的好处 和身体功能的影响。然而，目前还不清楚T 治疗可以增强运动对活动性和患者报告的功能的影响，或者是否有任何 所观察到的益处在积极治疗期之后持续存在。提出的是一个3组，多中心， 老年女性髋部骨折患者的随机、安慰剂对照、双盲、平行组临床试验 患者将使用客观筛选标准从6个临床研究中心入组300例女性髋部骨折患者 对于T缺乏（血清总睾酮水平< 30 ng/dl）和身体虚弱（改良的身体表现 测试（PPT）得分< 28）。该试验将比较监督运动训练（EX）单独，EX 联合T治疗（EX+T）和无EX+安慰剂T治疗（CON），以确定增加 在老年女性髋部骨折后ET基础上增加T的影响6个月的干预将遵循 为期6个月的无治疗可持续性阶段。主要的结果指标是六分钟步行 距离（6 MWD）。次要结局指标包括：1）双能X线骨密度仪（DXA） 测量全身和关节外LBM以及未骨折近端骨密度 股骨; 2）最大骨骼肌力量（1-RM）在双腿腿伸展; 3）客观的物理 性能指标;和4）自我报告的日常生活活动和生活质量的表现，包括 髋关节评分问卷（HRQ）。我们计划仔细监测睾丸激素水平，不良事件， 生化参数和与坚持干预措施相关的因素。 这项研究的信息有可能改变老年妇女髋部骨折的治疗， 这造成了严重的发病率和死亡率，并对公共卫生产生了巨大影响。拟议 这项研究与NIA的使命高度一致，即确定针对常见老年病的干预措施， 并改善患有多种疾病或风险因素的老年人的治疗选择。