PALS: Prostate Cancer Active Lifestyle Study

 描述（由申请方提供）：流行病学数据一致表明，肥胖与前列腺癌（PCa）进展风险增加相关，但因果机制的确定具有挑战性。肥胖和PCa进展之间的一个潜在联系是葡萄糖调节受损，这是一种有几种支持性证据的机制。糖尿病预防计划（DPP）是一种长期成功的既定生活方式干预。因此，DPP提供了一种新的策略来测试其改善PCa结局的能力，并对肥胖可能改变PCa进展的生物学途径产生见解。男性主动监测（AS），其中低风险PCa男性通过血液检查，体格检查和监测前列腺活检进行监测，代表了研究生活方式干预效果的理想人群。尽管命名为低风险，但这些患者中有50%会出现需要积极治疗的疾病进展。肥胖可能是导致疾病从低风险向高风险转变的主要因素之一。 我们假设，生活方式干预男性前列腺癌的AS将导致改善标志物的葡萄糖调节。为了验证这一假设，我们在200名选择AS的超重/肥胖（BMI > 25 kg/m2）PCa男性中进行了一项为期6个月的随机试验。患者将随机接受生活方式干预（基于DPP的结构化饮食/运动计划）或对照（基于美国一般饮食/体力活动指南的口头和书面信息）。本研究将针对以下具体目标：1.测试DPP生活方式干预（与对照相比）是否改善血清空腹血糖; 2.测试DPP生活方式干预（相对于对照）是否改善葡萄糖调节的血清生物标志物（胰岛素、C肽、胰岛素样生长因子-1（IGF-1）、IGF结合蛋白3（IGF-BP 3）和脂联素）; 3.检测DPP生活方式干预是否降低了随访前列腺活检时PCa组织上皮中胰岛素受体或胰岛素样生长因子-1受体（IGF-1 R）的水平; 4.检测随机分配至DPP生活方式干预组的PCa患者在干预结束后是否能维持生活方式改变至少6个月 期 我们还将评估DPP生活方式干预对健康相关生活质量和监测前列腺活检病理特征的影响。这项研究将解决当今男性最常见的两种诊断：肥胖和前列腺癌。随着越来越多的人认识到，许多患有前列腺癌的男性可能不需要积极治疗，而是可以通过AS方案进行监测，因此必须确定可改变的风险因素，以降低这些男性的疾病进展率。这项研究的结果可能对改善临床诊断为局部PCa的男性的总体和疾病特异性结局具有广泛的意义，并提供了积极生活方式的治疗选择 进行主动监视

 DESCRIPTION (provided by applicant): Epidemiologic data have consistently shown that obesity is associated with an increased risk of prostate cancer (PCa) progression, but identification of causal mechanisms has been challenging. One potential link between obesity and PCa progression is impaired glucose regulation, a mechanism for which there are several types of supportive evidence. The Diabetes Prevention Program (DPP) is an established lifestyle intervention with long-term success. Thus, the DPP offers a novel strategy to test its ability to improve PCa outcomes and yield insights on biological pathways through which obesity may modify PCa progression. Men on Active Surveillance (AS), where men with low risk PCa are monitored with blood tests, physical exams and surveillance prostate biopsies represent an ideal population to study the effects of a lifestyle intervention. Despite the nomenclature of low risk, 50% of these patients will experience disease progression requiring active treatment. Obesity may be one of the major factors leading to disease conversion from low to high risk. We hypothesize that a lifestyle intervention in men with PCa on AS will lead to improved markers of glucose regulation. To test this hypothesis we propose a 6-month randomized trial in 200 overweight/obese (BMI > 25 kg/m2) men with PCa who have elected AS. Patients will be randomized to either a lifestyle intervention (structured diet/exercise program based on the DPP); or control (oral and written information based on U.S. general dietary/physical activity guidelines). The study will address the following specific aims: 1. To test whether the DPP lifestyle intervention (vs. control) improves serum fasting glucose; 2. To test whether the DPP lifestyle intervention (vs. control) improves serum biomarkers of glucose regulation (insulin, C-peptide, insulin-like growth factor-1 (IGF-1), IGF binding protein 3 (IGF-BP3) and adiponectin); 3. To test whether the DPP lifestyle intervention decreases the levels of insulin receptor or insulin-like growth factor-1 receptor (IGF-1R) in PCa tissue epithelium on follow-up prostate biopsy; 4. To test whether PCa patients randomized to the DPP lifestyle intervention sustain the lifestyle changes for at least 6 months after the end of the intervention period. We will also evaluate the DPP lifestyle intervention effects on health-related quality of life and on pathologic features of the surveillance prostate biopsies. This study will address two of the most common diagnoses in men today: obesity and prostate cancer. With the growing recognition that many men with PCa may not require active treatment and can rather be monitored through AS protocols, it becomes imperative to identify modifiable risk factors for reducing the rate of disease progression in these men. Findings from this study may have wide reaching implications in improving both the overall and disease-specific outcomes in men diagnosed with clinically localized PCa, and provide a treatment alternative of an active lifestyle for active surveillance.