Alternate Therapies for Benign Prostate Symptoms

描述（由申请人提供）： 由良性前列腺增生（BPH）引起的下尿路症状（LUTS）在老年男性中非常常见，并且在发病率和卫生保健资源利用方面都带来了相当大的卫生保健负担。除了标准的经尿道前列腺切除术（TURP）外，在过去十年中还开发了微创手术治疗（MIST），并在不同程度上使用。此外，目前有三类药物用于治疗LUTS和BPH：α肾上腺素能受体阻滞剂、5 α还原酶抑制剂（5 ARI）和植物治疗剂。持续时间长达12个月的RCT和持续时间长达60个月的开放标签扩展试验支持使用α受体阻滞剂。持续时间长达48个月的RCT和长达72个月的开放标签扩展试验支持使用5种ARI。持续时间在许多不同的植物治疗制剂中，很少有在随机安慰剂对照试验中进行研究，通常持续时间为6个月或更短。最常用的制剂是锯棕榈提取物，它已经经历了最广泛的测试，包括长达12个月的随机试验，直接与α受体阻滞剂进行比较，但不是与安慰剂进行比较。鉴于这些非处方制剂的广泛使用，迫切需要关于最常用化合物的相对安全性和有效性的数据。该联盟的目的是开发和开展涉及这些化合物的相关临床试验。拟在参与中心进行一项为期4 - 6年的随机、安慰剂对照试验，研究锯木提取物和非洲臀果木，入组约3，000例患者，目的如下：确定锯棕榈和非洲臀果木与安慰剂相比在预防定义的LUTS和BPH进展方面的疗效（1）作为AUA症状指数较基线增加4分或更多分的两次验证，（2）作为自发性或突发性急性尿潴留（AUR）的发生，（3）作为BPH需要MIST或手术治疗伴或不伴既往AUR发作，（4）由于肾功能不全（由于BPH）、复发性尿路感染（UTI）（由于BPH）或尿失禁的发展。(5)确定锯棕榈和非洲臀果木与安慰剂相比在改善AUA SI、其他人文问卷、性功能、总体主观评估和从基线至研究结束的最大尿流率方面的疗效。(7)确定基线参数是否能够预测对不同治疗的反应。(8)确定与安慰剂相比，锯棕榈或非洲臀果木是否诱导前列腺体积、移行区体积、血清PSA和其他基于BPH的血清或组织生物标志物的可测量变化。

DESCRIPTION (provided by applicant): Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) are very common findings in aging men and present a considerable health care burden both in terms of morbidity as well as health care resource utilization. Aside from the standard therapy transurethral resection of the prostate (TURP), minimally invasive surgical therapies (MIST) have been developed over the past decade, which are utilized to varying degrees. In addition, three classes of medications are currently being utilized for the treatment of LUTS and BPH: alpha adrenergic receptor blocker, 5 alpha reductase inhibitors (5 ARI), and phytotherapeutic agents. The use of alpha blocker is supported by RCTs of up to 12 mo duration and open label extension trials up to 60 mo duration. Use of the 5 ARI is supported by RCTs of up to 48 mo duration and open label extension trials up to 72 mo. duration. Of the many different phytotherapeutic preparations available, few have been studied in randomized placebo-controlled trials usually 6 mo or shorter in duration. The most commonly used preparation is saw palmetto extract, which has undergone the most extensive testing including randomized trials of up to 12 mo duration in direct comparison to an alpha blocker, however, not against placebo. Given the widespread use of these over the counter preparation data regarding the relative safety and efficacy of the most commonly used compounds are urgently needed. The purpose of the consortium is to develop and carry out a relevant clinical trial involving these compounds. A randomized, placebo-controlled trial of saw pametto extract and pygeum africanum with a 4 to 6 yrs follow-up period is proposed enrolling approx 3,000 patients at the participating centers with the following objectives: Determine the efficacy.of saw palmetto and pygeum africanum compared with placebo in preventing the progression of LUTS and BPH defined (1) as a twice validated increase in the AUA Symptom Index by four or more points from baseline, (2) as the development of either spontaneous or precipitated acute urinary retention (AUR), (3) as the need for MIST or surgical therapy for BPH with or without a preceding episode of AUR, (4) as the development of renal insufficiency ( due to BPH), recurrent urinary tract infection (UTI) (due to BPH), or incontinence. (5) Determine the efficacy of saw palmetto and pygeum africanum compared with placebo in terms of improving the AUA SI, other humanistic questionnaires, sexual functioning, global subjective assessment and maximum urinary flow rate from baseline to end of study. (7) Determine whether baseline parameters are able to predict response to the different therapies administered. (8) Determine whether saw palmetto or pygeum africanum compared to placebo induce measurable changes in prostate volume, transition zone volume, serum PSA and other serum or tissue based biomarkers of BPH.