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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一个研究者发起的，行业赞助的协议它是由Harbor的研究者们大量投入构思出来的。这是一项多中心研究，研究对象为60-80岁血清睾酮水平低且性腺功能减退的男性。大约有120名患者（每个治疗组40名）。他们将被给予35毫克/天，70毫克/天的双氢睾酮凝胶，或安慰剂凝胶。所有受试者每天使用一次凝胶。本研究的主要疗效终点是瘦体质量（LBM）的增加，这是由DEXA（一种用于测量骨矿物质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、肌肉力量、性功能、衰老男性症状量表、生活质量、正常睾酮水平、认知、情绪和临床医生对变化的总体印象的变化。这项研究将持续六个月。在受试者被随机分配接受研究药物之前，他将经历一个筛选阶段，包括同意过程、体检、血液检查、尿液检查和心电图（EKG）。如果所有筛查结果都在正常范围内，受试者将被随机分配接受35mg /d、70mg /d DHT或安慰剂凝胶。在基线检查时，他们还将接受前列腺超声、血液检查、DEXA、肌肉力量测试和6分钟步行测试。受试者将于第1、3和6个月返回GCRC进行血液检查（测量激素水平）、完成问卷、生命体征评估和凝胶应用领域评估。在每次访问前完成一份为期七天的日记，记录性欲、勃起和酒精摄入量。体检将在第3个月和第6个月进行。前列腺超声检查将在第6个月（研究结束）再次进行。在第2个月、第4个月和第5个月，研究对象将通过电话询问他们的日常凝胶治疗以及他们的健康和药物的任何变化。为这项研究抽取的血液总量将少于一品脱。患者可能受益于雄激素替代疗法的效果，包括改善性功能和增加瘦体重和骨厚度。应用二氢睾酮后预期达到的总雄性激素（DHT +睾酮）水平将在成年男性总雄激素水平的生理范围内。除了轻微的体重增加、皮肤油腻、痤疮和皮肤刺激外，受试者不太可能出现任何临床显著的副作用。其他可能的副作用包括：红细胞增多、乳房胀痛、腿部肿胀、胆固醇水平改变、前列腺增大和尿流阻塞症状。没有明确的证据表明男性荷尔蒙会导致前列腺癌。研究人员将对男性进行血清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。研究前有排尿困难症状的男性不符合参加研究的资格。使用DHT的女性伴侣长时间的皮肤接触可能会导致伴侣面部毛发的轻微增加。患者在与女性和儿童密切接触前应穿防护服或淋浴。它必须放在妇女、儿童和没有阅读和理解能力的人拿不到的地方。如上所述，我们预计筛选和招募120名受试者，并在加州大学洛杉矶分校海港分校随机抽取不超过40名受试者。然而，除了Harbor-UCLA之外，这项研究还将在另外两个中心进行，并且从这三个中心随机抽取的120名受试者的所有激素检测都将在GCRC或研究者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方法雄激素替代老化，性腺功能低下的男性。虽然DHT是前列腺内最丰富的男性激素，但没有证据表明外源性DHT会增加前列腺内DHT水平。相反，有观点认为，由于DHT不能转化为雌性激素，而且老年男性前列腺肥大的发展需要雄性激素和雌性激素，因此DHT对前列腺生长的促进作用不如睾丸激素本身。

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.