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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这是一项由调查人员发起、由行业赞助的协议，它是由港湾的调查人员提供大量投入而构思的。这是一项针对60-80岁的男性受试者的多中心研究，这些受试者有低血清睾酮和性腺功能减退的症状。将有大约120名患者(每个治疗组40名)。他们将被给予35毫克/天、70毫克/天的双氢睾丸酮(DHT)凝胶或安慰剂凝胶。所有受试者每天都要涂一次凝胶。这项研究的主要疗效终点是瘦体重(LBM)的增加，这是由DEXA(一种用于测量骨密度和全身成分的机器)确定的。本研究的次要终点包括性欲、肌力、性功能、老年男性症状量表、生活质量、正常睾酮水平、认知、情绪以及临床医生对变化的总体印象。 这项研究将在六个月内进行。在随机接受研究药物之前，受试者将经历一个筛选阶段，其中包括同意过程、体检、血液测试、尿检和心电图(EKG)。如果所有筛查结果都在正常范围内，受试者将被随机接受35 mg/d、70 mg/d DHT或安慰剂凝胶。在基线访问中，他们还将接受前列腺超声、血液测试、DEXA、肌肉力量测试和6分钟步行测试。 受试者将在1、3和6个月返回GCRC进行血液测试(测量激素水平)、完成问卷调查、生命体征评估和凝胶应用领域的评估。在每次探视之前，将完成一份为期七天的日记，记录性欲、勃起和酒精摄入量。在3个月和6个月进行体格检查。在6个月(学习结束)时重复进行前列腺超声检查。在2个月、4个月和5个月时，受试者将被打电话询问他们每天的凝胶治疗情况以及他们的健康和药物治疗的任何变化。 这项研究的总抽血量将不到一品脱。 患者可能受益于雄激素替代治疗的效果，包括改善性功能，增加瘦体重和骨厚度。 在应用DHT后达到的预期总雄激素(DHT加睾酮)水平将在成年男性总雄激素水平的生理范围内。受试者不太可能经历任何临床上显著的副作用，除了轻微的体重增加、皮肤油性、粉刺和皮肤刺激。其他可能的副作用包括：红细胞增加，乳房压痛，腿部肿胀，胆固醇水平变化，前列腺增大和尿流障碍症状。没有明确的证据表明男性荷尔蒙会导致前列腺癌。男性将接受血清PSA水平的跟踪，并在基线和研究结束时进行前列腺超声检查。研究前出现排尿困难症状的男性将没有资格参加。在使用DHT的情况下，女性伴侣长时间的皮肤接触可能会导致伴侣面部毛发轻微增加。患者在与女性和儿童近距离接触之前将穿上防护服或洗澡。它必须放在妇女、儿童和不识字、不理解的人够不到的地方。 如上所述，我们预计在港湾-加州大学洛杉矶分校筛选和招募120名受试者，随机选择不超过40名受试者。然而，这项研究将在除港湾-加州大学洛杉矶分校之外的另外两个中心进行，从所有三个中心随机抽取的120名受试者的所有激素分析将在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新的经皮途径，用于老年性腺功能低下男性的雄激素替代。虽然DHT是前列腺中含量最丰富的男性激素，但没有证据表明外源性DHT会增加前列腺中的DHT水平。相反，有人认为，由于DHT不能转化为女性激素，而且老年男性的前列腺肥大发展需要男性和女性激素，所以DHT对前列腺生长的促进作用不如睾酮本身。