A PHASE II, PLACEBO-CONTROLLED, DOUBLE-BLIND, DOSE-RANGING (35MG/D OR 70MG/D)

A 期、安慰剂对照、双盲、剂量范围（35MG/D 或 70MG/D）

• 批准号: 7606180
• 负责人: RONALD Sherwin SWERDLOFF
• 金额: $ 1.44万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606180
• 关键词: Acne; Adult; Adverse effects; Age; Aging; Alcohol consumption; Androgens; Area; Biological Assay; Blood; Blood Tests; Body Composition; Bone Density; Breast; Cancer Etiology; Child; Cholesterol; Cognition; Computer Retrieval of Information on Scientific Projects Database; Consent; DEXA; Daily; Development; Dose; Double-Blind Method; Electrocardiogram; End Point; Endocrine; Enrollment; Erythrocytes; Face; Female; Funding; Gel; Grant; Growth; Hair; Health; Hormones; Hypogonadism; Industry; Institution; Laboratory Research; Leg; Libido; Malignant neoplasm of prostate; Measures; Methods; Moods; Normal Range; Obstruction; PSA level; Patients; Persons; Pharmaceutical Preparations; Phase; Physiological; Placebo Control; Placebos; Pre-study; Prostate; Protective Clothing; Protocols documentation; Quality of life; Questionnaires; Randomized; Range; Reading; Replacement Therapy; Research; Research Personnel; Resources; Screening Result; Screening procedure; Serum; Sex Functioning; Skin; Source; Stanolone; Suggestion; Swelling; Symptoms; Telephone; Testing; Testosterone; Thick; Ultrasonography; United States National Institutes of Health; Urine; Visit; Walking; Weight Gain; Woman; bone; clinically significant; day; desire; diaries; erection; experience; impression; male; men; muscle strength; older men; physical process; prostate enlargement; serum PSA; size; skin irritation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is an investigator initiated, industry sponsored protocol which was conceived with significant input by the investigators at Harbor. This is a multi-center study in male subjects ages 60-80 who have low serum testosterone and symptoms of hypogonadism. There will be approximately 120 patients (40 in each treatment group). They will be given 35 mg/d, 70 mg/d dihydrotestosterone (DHT) gel, or a placebo gel. All subjects will apply the gel once daily. The primary efficacy endpoint in this study is an increase in Lean Body Mass (LBM) as determined by the DEXA (a machine used to measure bone mineral density and total body composition). Secondary endpoints in this study include changes in Libido, muscle strength, sexual function, aging male symptom scale, quality of life, normal testosterone levels, cognition, mood, and clinician's global impression of change. The study will occur over a six-month period. Before the subject is randomized to receive study medications, he will undergo a screening phase, which includes the consent process, physical exam, blood tests, urine tests, and an electrocardiogram (EKG). If all results of the screening are found to be within the normal range, the subject will be randomized to receive either 35 mg/d, 70 mg/d DHT or placebo gel. They will also undergo a prostate ultrasound, blood test, DEXA, muscle strength testing and a six-minute walk test, at the baseline visit. Subjects will return to the GCRC on months 1, 3, and 6, for blood tests (to measure hormone levels), completion of questionnaires, vital sign assessment, and assessment of gel application areas. A seven-day diary will be completed prior to each visit to record sexual desire, erections, and alcohol intake. Physical exam will be done at months 3 and 6. An prostate ultrasound will be repeated at month 6 (end of study). At months 2, 4, and 5, subjects will be telephoned to inquire about their daily gel treatment and any changes in their health and medications. The total amount of blood drawn for the study will be less than a pint. The patient may benefit from the effects of androgen replacement therapy including improvement in sexual function and an increase of lean body mass and bone thickness. The anticipated total male hormone (DHT plus testosterone) levels achieved after DHT application will be within the physiologic range of the total androgen level in adult men. It is unlikely that the subjects will experience any clinically significant side effects, except for mild weight gain, oiliness of skin, acne, and skin irritation. Other possible side effects include: increase in red blood cells, breast tenderness, leg swelling, changes in cholesterol levels, increase in prostate size and symptoms of obstruction to urine flow. There is no clear evidence that shows that male hormones cause cancer of the prostate. Men will be followed with serum PSA levels and prostate ultrasound will be done at baseline and end of study. Men with pre-study symptoms of difficulty in urinating will not be eligible to participate. Prolonged skin contact by the female partner where DHT is applied may result in some slight increase of facial hair in the partner. Patients will wear protective clothing or showered before close contact with females and children. It must be kept out of reach from women, children, and persons with inability to read and understand. As mentioned above, we anticipate screening and enrolling 120 subjects and randomizing no more than 40 subjects here at Harbor-UCLA. However, this study will be done at two other centers, besides Harbor-UCLA, and all hormone assays from the 120 subjects randomized from all three centers will be done at the GCRC or the Endocrine Research Laboratory of the investigators. This study will help develop a new transdermal method for androgen replacement for aging, hypogonadal men. Although DHT is the most abundant male hormone within the prostate, there is no evidence that administration of exogenous DHT will increase the DHT levels in the prostate. On the contrary there have been suggestions that as DHT cannot be converted to the female hormone and as both male and female hormones are required for the development of prostate enlargement in older men, DHT has been suggested to have less prostate growth promoting effect than testosterone itself.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 这是一项研究人员发起的行业赞助协议，港口调查人员的大量投入构想。 这是一项多中心的研究，对血清睾丸激素低的60-80岁男性受试者和性交症状。 大约有120名患者（每个治疗组中有40例）。 它们将获得35 mg/d，70 mg/d二氢睾丸激素（DHT）凝胶或安慰剂凝胶。 所有受试者将每天应用一次凝胶。 这项研究中的主要功效终点是由DEXA（用于测量骨矿物质密度和总体组成的机器）确定的瘦体重（LBM）的增加。 这项研究的次要终点包括性欲，肌肉力量，性功能，男性症状量表，生活质量，正常睾丸激素水平，认知，情绪和临床医生对变化的全球印象。 该研究将在六个月内进行。 在受试者被随机接受学习药物之前，他将进行筛查阶段，其中包括同意过程，体格检查，血液检查，尿液检查和心电图（EKG）。 如果发现所有筛选结果都在正常范围内，则将随机分配受试者以接收35 mg/d，70 mg/d DHT或安慰剂凝胶。 他们还将在基线访问时进行前列腺超声检查，血液测试，DEXA，肌肉力量测试和六分钟的步行测试。 受试者将在第1、3和第6个月返回GCRC，进行血液检查（测量激素水平），问卷的完成，生命体征评估以及凝胶施用区域的评估。 每次访问之前将完成七天的日记，以记录性欲，勃起和酒精摄入量。 身体检查将在第3和第6个月进行。将在第6个月（研究结束）重复前列腺超声检查。在第2、4和5个月，将打电话给受试者，以询问他们的日常凝胶治疗以及其健康和药物的任何变化。 研究的总血液量将小于品脱。 患者可能会受益于雄激素替代疗法的影响，包括改善性功能以及瘦体重和骨骼厚度的增加。 DHT应用后达到的预期雄性激素（DHT加睾丸激素）水平将在成年男性总雄激素水平的生理范围内。 受试者不太可能会出现任何临床上显着的副作用，除了轻度的体重增加，皮肤油脂，痤疮和皮肤刺激。 其他可能的副作用包括：红细胞的增加，乳房压痛，腿部肿胀，胆固醇水平的变化，前列腺大小的增加以及尿液流动的阻塞症状。 没有明确的证据表明雄性激素会导致前列腺癌。 男性将在基线和研究结束时进行血清PSA水平，前列腺超声将进行。在尿液中出现困难症状的男性将没有资格参加。 应用DHT的女性伴侣长时间的皮肤接触可能会导致伴侣的面部毛发略有增加。在与女性和儿童密切接触之前，患者将穿防护服或淋浴。妇女，儿童和无法阅读和理解的人必须远离妇女，儿童和人。 如上所述，我们预计在Harbour-Ucla将进行筛查和注册120名受试者，并随机对40名受试者进行随机化。 但是，这项研究将在其他两个中心（除港口 - 乌加克拉岛）外进行，所有三个中心随机的120名受试者的激素测定法将在GCRC或研究人员的内分泌研究实验室进行。 这项研究将有助于开发一种用于衰老的雄激素替代的新的透皮方法。尽管DHT是前列腺中最丰富的雄性激素，但没有证据表明外源DHT的给药会增加前列腺中的DHT水平。相反，有人建议，由于DHT不能转化为雌性激素，并且由于男性和女性激素在老年男性中的发展需要雄性和女性激素，因此，DHT被认为比睾丸激素本身具有较少的前列腺增长促进作用。