Alternate Therapies for Benign Prostate Symptoms

描述(由申请人提供)： 由良性前列腺增生症(BPH)引起的下尿路症状(LUTS)在老年男性中非常常见，在发病率和医疗资源利用方面都造成了相当大的医疗负担。除了标准的经尿道前列腺电切术(TURP)外，微创手术疗法(MIST)在过去十年中得到了发展，并得到了不同程度的利用。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、5α还原酶抑制剂(5 ARI)和植物治疗药物。阿尔法阻滞剂的使用得到了持续时间长达12个月的随机对照试验和持续时间长达60个月的开放标签延长试验的支持。5个ARI的使用得到持续时间长达48个月的RCT和长达72个月的开放标签延长试验的支持。持续时间。在现有的许多不同的植物治疗制剂中，很少有人在随机安慰剂对照试验中进行研究，这些试验的持续时间通常为6个月或更短。最常用的制剂是锯棕榈提取物，它经过了最广泛的测试，包括随机试验，持续时间长达12个月，直接与阿尔法阻滞剂进行比较，而不是与安慰剂进行比较。鉴于这些药物在场外的广泛使用，迫切需要有关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进行涉及这些化合物的相关临床试验。一项随机、安慰剂对照的试验--SAW帕美托提取物和非洲腐乳，在参与中心招募了大约3000名患者，随访期为4-6年，目的如下：确定SAW棕榈和非洲腐乳与安慰剂在预防LUTS和BPH进展方面的有效性，定义(1)AUA症状指数比基线增加两次，增加4个或更多点，(2)发展为自发性或诱发性急性尿潴留(AUR)，(3)需要雾化或手术治疗BPH，有或没有AUR发作，(4)发展为肾功能不全(由BPH引起)、反复尿路感染(因BPH引起)或尿失禁。(5)从改善AUA指数、其他人文问卷、性功能、总体主观评价和最大尿流率等方面，确定SAW棕榈和非洲腐乳与安慰剂的疗效比较。(7)确定基线参数是否能够预测对不同疗法的反应。(8)确定与安慰剂相比，锯棕榈或非洲鬼臼是否会导致前列腺体积、移行区体积、血清PSA和其他基于血清或组织的BPH生物标志物发生可测量的变化。

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.