The Bone Trial of the Testosterone Trial

睾酮试验的骨骼试验

• 批准号: 8507119
• 负责人: PETER J. SNYDER
• 金额: $ 52.41万
• 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 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8507119
• 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.

描述(申请人提供)：睾酮试验是一个随机、安慰剂对照的小组，由6个密切协调的试验组成，在800名65岁的男性中进行，他们明确地表明，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。睾丸激素试验已经得到资助，预计将于2010年夏天开始招募受试者。我们建议在参加睾酮试验的200名男性中增加一项骨骼试验。骨试验的理由是，尽管有明确的证据表明，睾酮可以极大地改善因已知的垂体或睾丸疾病而导致性腺功能严重低下的男性的骨小梁密度和强度，但对于睾酮缺乏程度较轻的老年男性，睾酮改善骨骼的证据是模棱两可的。我们建议利用睾酮试验中那些被招募和筛查并被发现血清睾酮浓度明确较低的男性的可用性，并同意参与这项试验，以明确确定睾酮治疗是否会改善他们的骨骼质量。这项试验的总体特定目标是验证这样一种假设，即在血清睾酮浓度为275 ng/dL的65岁男性中，睾酮治疗一年比服用安慰剂更能改善骨骼质量。主要的特定终点是通过定量计算机断层扫描(QCT)测量脊柱的体积骨密度(VBMD)。次要终点是髋部的vBMD；QCT数据通过有限元分析确定的脊柱和髋部的骨强度和强度/密度比；DXA测量的腰椎、髋部近端和桡骨远端的面骨密度；骨转换的血清标志物；以及临床骨折。受试者(200人)将从符合睾丸激素试验其中一项试验条件的男性中招募，这些人没有疾病，也没有服用任何已知会影响骨骼的药物。他们将随机接受睾丸素或安慰剂凝胶的双盲治疗，为期一年。在基线和12个月时进行脊柱、髋部和桡骨远端的QCT和DXA检查。骨标记物将在基线、1、2、3、6和12个月时进行测定。临床骨折将在3、6、9、12、18和24个月进行评估。骨骼试验的意义在于，它将是第一个评估睾酮对睾酮水平较低的男性的体积骨密度的影响的研究，更重要的是，它对骨骼强度的影响。证明睾酮可以改善这些男性的骨骼强度，这将为进行更大、更长时间的试验提供理论基础，以确定睾酮治疗是否也能减少临床骨折。骨试验还将提供有关临床骨折的数据，这将使更大、更长试验的样本量估计成为可能。