The proposal is a response for a research project (cooperative agreement) by the NIH-NIDDK for consideration for one of 14 Clinical Centers in an expanded trial of Medical Therapy in Benign Prostatic Hyperplasia (BPH). This trial is a prospective, multi-center, randomized placebo controlled, double masked clinical study to assess if finasteride and/or doxazosin delays or prevents the progression of BPH. Health Relatedness: BPH is the most common neoplastic condition afflicting men and constitutes a major factor impact Americans. Bladder neck obstruction secondary to BPH can result in renal failure, disruptive bladder symptoms, urinary retention, UTI, bladder stones and hematuria. Current studies estimate 30% of American males will require a surgical procedure to correct this problem sometime in their life. The concept that medical therapy will delay BPH is attractive based on the short term data available. This study will be crucial to answering that question as well as others pertaining to the progression of BPH.
Specific Aims : Alpha receptor blockage (ARB) and finasteride (FIN) are currently used to reduce the smooth muscle tone and prostate mass (respectively) in the pharmacologic management of BPH. The primary aim of this study to address whether ARB and/or FIN alter BPH progression or simply delay the time to surgical therapy. The data accumulated should provide evidence regarding long term effects of these therapies on objective parameters of BPH including the AUA symptom score, maximal urinary flow rates, or prostate size and how these medications compare in their impact on the same. Design and Method: In four treatment arms 200 patients with symptoms of BPH will be assigned to either FIN, FIN and ARB, ARB or placebo and followed for 4-6 years. Progression parameters will include: l) changes in the AUA symptom score, 2) urinary retention, 3) recurrent UTI, 4) renal insufficiency, 5) urinary incontinence or 6) crossover to known therapy. Objective parameters of BPH will include prostate size, maximal urinary flow rates, and AUA symptom score. Secondary Aim: Unique to this submission is whether a chief complaint analysis or global health scale provides reliable or useful information in addition to that obtained from the AUA symptom score. Additionally, the issue of treatment related physiologic changes in the composition of prostatic secretions predicting BPH progression is worthy of investigation.
|Kaplan, Steven A; Lee, Jeannette Y; O'Neill, Edward A et al. (2013) Prevalence of low testosterone and its relationship to body mass index in older men with lower urinary tract symptoms associated with benign prostatic hyperplasia. Aging Male 16:169-72|
|Kaplan, Steven A; Lee, Jeannette Y; Meehan, Alan G et al. (2011) Long-term treatment with finasteride improves clinical progression of benign prostatic hyperplasia in men with an enlarged versus a smaller prostate: data from the MTOPS trial. J Urol 185:1369-73|
|Kaplan, Steven A; Roehrborn, Claus G; McConnell, John D et al. (2008) Long-term treatment with finasteride results in a clinically significant reduction in total prostate volume compared to placebo over the full range of baseline prostate sizes in men enrolled in the MTOPS trial. J Urol 180:1030-2;discussion 1032-3|
|Crawford, E David; Wilson, Shandra S; McConnell, John D et al. (2006) Baseline factors as predictors of clinical progression of benign prostatic hyperplasia in men treated with placebo. J Urol 175:1422-6; discussion 1426-7|
|Kaplan, Steven A; McConnell, John D; Roehrborn, Claus G et al. (2006) Combination therapy with doxazosin and finasteride for benign prostatic hyperplasia in patients with lower urinary tract symptoms and a baseline total prostate volume of 25 ml or greater. J Urol 175:217-20; discussion 220-1|
|McVary, Kevin T; Rademaker, Alfred; Lloyd, Granville L et al. (2005) Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 174:1327-433|
|McConnell, John D; Roehrborn, Claus G; Bautista, Oliver M et al. (2003) The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 349:2387-98|