The Bone Trial of the Testosterone Trial

睾酮试验的骨骼试验

• 批准号: 8108871
• 负责人: PETER J. SNYDER
• 金额: $ 73.94万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8108871
• 关键词: Affect; Age; Anemia; Area; Bone Density; Clinical; Clinical Trials; Cognition; Control Groups; Data; Disease; Distal; Dual-Energy X-Ray Absorptiometry; Elderly; Elderly man; Enrollment; Finite Element Analysis; Fracture; Funding; Gel; Hip Fractures; Hip region structure; Hypogonadism; Incidence; Institute of Medicine (U.S.); Measures; Methods; Morphologic artifacts; Osteoporosis; Pharmaceutical Preparations; Physical Function; Pituitary Diseases; Placebo Control; Placebos; Play; Public Health; Qualifying; Radial; Randomized; Recruitment Activity; Reporting; Risk; Role; Sample Size; Schedule; Serum; Serum Markers; Sex Functioning; Spinal Fractures; Testicular Diseases; Testing; Testosterone; United States National Institutes of Health; Vertebral column; Woman; X-Ray Computed Tomography; bone; bone quality; bone strength; bone turnover; calcification; cardiovascular risk factor; density; falls; human old age (65+); improved; men; older men; response; substantia spongiosa

DESCRIPTION (provided by applicant): The Testosterone Trial is a randomized, placebo-controlled group of six closely coordinated trials in 800 men >65 years old who have unequivocally low serum testosterone of the effect of testosterone treatment for one year on physical function, sexual function, vitality, cognition, anemia and cardiovascular risk. The Testosterone Trial has been funded and is expected to begin enrolling subjects in the summer of 2010. We propose adding a Bone Trial in a subset of 200 men who enroll in The Testosterone Trial. The rationale for The Bone Trial is that although the evidence is clear that testosterone greatly improves trabecular bone density and strength in men who are severely hypogonadal due to known pituitary or testicular disease, the evidence that testosterone improves bone in elderly men who have more modest degrees of testosterone deficiency is equivocal. We propose taking advantage of the availability of men in The Testosterone Trial who have been recruited and screened and found to have unequivocally low serum testosterone concentrations and have agreed to participate in this trial to determine definitively if testosterone treatment will improve their bone quality. The overall specific aim of this trial is to test the hypothesis that testosterone treatment for one year will improve bone quality more than placebo in men >65 years who have serum testosterone concentrations <275 ng/dL. The primary specific end point is volumetric bone mineral density (vBMD) of the spine by quantitated computed tomography (QCT). Secondary end points are vBMD of the hip; bone strength and strength-to-density ratio in the spine and hip by finite element analysis determined from the QCT data; areal BMD of the lumbar spine, proximal hip and distal radius by DXA; serum markers of bone turnover; and clinical fractures. Subjects (200) will be recruited from among men who have qualified for one of the trials in The Testosterone Trial and who have no diseases and are taking no medications known to affect bone. They will be randomized to receive testosterone or placebo gel double blindly for one year. QCT and DXA of the spine, hip and distal radius will be performed at baseline and 12 months. Bone markers will be determined at baseline, 1, 2, 3, 6, and 12 months. Clinical fractures will be assessed at 3, 6, 9, 12, 18 and 24 months. The significance of The Bone Trial is that it would be the first study to assess the effect of testosterone on volumetric BMD in men >65 with low testosterone and, more importantly, on bone strength. Demonstration that testosterone improves bone strength in these men would provide the rationale for a larger, longer trial to determine if testosterone treatment reduces clinical fractures as well. The Bone Trial will also provide data on clinical fractures that will allow sample size estimation for a larger, longer trial. PUBLIC HEALTH RELEVANCE: The significance of The Bone Trial is that it would be the first study to assess the effect of testosterone on volumetric BMD in men >65 with low testosterone and, more importantly, the first to assess the effect of testosterone on bone strength in these men. Demonstration that testosterone could improve bone strength in these men would be a major impetus to a long-term trial to determine if testosterone treatment would reduce clinical fractures as well. The Bone Trial could therefore be the first major step in determining if testosterone treatment could ameliorate the increasing public health burden of fractures in older men.

描述（由申请人提供）：Tequillo试验是一项随机、安慰剂对照组的6项密切协调的试验，在800名年龄>65岁的男性中进行，这些男性血清睾酮明显较低，睾酮治疗一年对身体功能、性功能、活力、认知、贫血和心血管风险的影响。Tehran试验已获得资金，预计将于2010年夏季开始招募受试者。我们建议在200名男性中增加一项骨试验，这些男性参加了Tehran试验。骨试验的基本原理是，尽管有证据表明，睾酮大大改善了由于已知的垂体或睾丸疾病而严重性腺功能减退的男性的骨小梁密度和强度，但睾酮改善中度睾酮缺乏的老年男性骨的证据是不明确的。我们建议利用在Tehran试验中招募和筛选的男性的可用性，并发现血清睾酮浓度明显较低，并同意参加这项试验，以明确确定睾酮治疗是否会改善他们的骨质量。本试验的总体具体目的是检验以下假设：在血清睾酮浓度<275 ng/dL的>65岁男性中，睾酮治疗一年将比安慰剂更能改善骨质量。主要的特异性终点是通过定量计算机断层扫描（QCT）测量脊柱的体积骨矿物质密度（vBMD）。次要终点是髋关节vBMD;通过QCT数据确定的有限元分析确定的脊柱和髋关节骨强度和强度-密度比;通过DXA确定的腰椎、髋关节近端和桡骨远端的区域BMD;骨转换的血清标志物;和临床骨折。受试者（200例）将从符合Tehran试验中一项试验的资格且无疾病且未服用已知影响骨骼的药物的男性中招募。他们将随机接受睾酮或安慰剂凝胶双盲一年。将在基线和12个月时对脊柱、髋关节和桡骨远端进行QCT和DXA。将在基线、1、2、3、6和12个月时测定骨标志物。将在3、6、9、12、18和24个月时评估临床骨折。骨试验的意义在于，它将是第一项评估睾酮对65岁以上低睾酮男性的体积BMD影响的研究，更重要的是，对骨强度的影响。证明睾酮可以改善这些男性的骨强度，这将为更大规模、更长时间的试验提供依据，以确定睾酮治疗是否也能减少临床骨折。骨试验还将提供临床骨折的数据，这将允许更大、更长试验的样本量估计。 公共卫生关系：骨试验的意义在于，它将是第一项评估睾酮对65岁以上低睾酮男性体积BMD影响的研究，更重要的是，第一项评估睾酮对这些男性骨强度影响的研究。证明睾酮可以改善这些男性的骨强度，这将是一个长期试验的主要动力，以确定睾酮治疗是否也会减少临床骨折。因此，骨试验可能是确定睾酮治疗是否可以减轻老年男性骨折日益增加的公共卫生负担的第一个重要步骤。