PALS: Prostate Cancer Active Lifestyle Study

PALS：前列腺癌积极生活方式研究

• 批准号: 9282571
• 负责人: Jonathan L. Wright
• 金额: $ 61.06万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9282571
• 关键词: Accounting; Address; Adverse effects; Animal Model; Anxiety; Behavior Therapy; Biological; Biological Markers; Blood Tests; Body Weight; Body Weight decreased; C-Peptide; Cancer Etiology; Cancer Patient; Cancer Survivor; Cessation of life; Clinical; Data; Diabetes Mellitus; Diagnosis; Diet; Disease; Disease Progression; Epithelium; Expenditure; Glucose; Guidelines; Health; Health Benefit; Health Care Costs; Human; Hyperglycemia; Hyperinsulinism; Impairment; In Vitro; Individual; Insulin; Insulin Receptor; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin-Like-Growth Factor I Receptor; Intervention; Knowledge; Lead; Level of Evidence; Life Style; Link; Malignant Neoplasms; Malignant neoplasm of prostate; Monitor; Morbidity - disease rate; Nomenclature; Obesity; Oral; Outcome; Overweight; Participant; Pathologic; Pathway interactions; Patient Monitoring; Patient-Focused Outcomes; Patients; Physical activity; Population; Protocols documentation; Public Health; Randomized; Risk; Risk Factors; Serum; Structure; Testing; Tissues; Tumor Tissue; active method; adiponectin; adverse outcome; alternative treatment; base; blood glucose regulation; cancer diagnosis; cardiovascular disorder risk; clinical practice; diabetes prevention program; diabetes risk; diet and exercise; disorder risk; epidemiologic data; exercise intervention; exercise program; experience; fasting glucose; feeding; follow-up; health related quality of life; healthy weight; high risk; improved; insight; intervention effect; lifestyle intervention; men; modifiable risk; mortality; novel strategies; overexpression; polypeptide C; prevent; prostate biopsy; prostate cancer cell; public health relevance; randomized trial; success; tissue biomarkers; tumor; tumor growth; tumor progression

 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.

 描述（由申请人提供）：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，但确定因果机制一直具有挑战性。肥胖与 PCa 进展之间的一个潜在联系是葡萄糖调节受损，这种机制有多种类型的支持性证据。糖尿病预防计划 (DPP) 是一项既定的生活方式干预措施，取得了长期成功。因此，DPP 提供了一种新策略来测试其改善 PCa 结果的能力，并深入了解肥胖可能改变 PCa 进展的生物学途径。接受主动监测 (AS) 的男性是研究生活方式干预效果的理想人群，通过血液检查、体检和前列腺活检监测来监测患有低风险 PCa 的男性。尽管命名为低风险，但其中 50% 的患者会出现疾病进展，需要积极治疗。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。 我们假设对患有 AS 的 PCa 男性进行生活方式干预将导致血糖调节指标的改善。为了检验这一假设，我们建议对 200 名患有 PCa、选择 AS 的超重/肥胖 (BMI > 25 kg/m2) 男性进行为期 6 个月的随机试验。患者将被随机分配接受生活方式干预（基于 DPP 的结构化饮食/运动计划）；或控制（基于美国一般饮食/身体活动指南的口头和书面信息）。该研究将解决以下具体目标： 1. 测试 DPP 生活方式干预（与对照）是否改善血清空腹血糖； 2. 测试DPP生活方式干预（与对照）是否改善血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-BP3）和脂联素）； 3. 检测后续前列腺活检中DPP生活方式干预是否降低PCa组织上皮中胰岛素受体或胰岛素样生长因子-1受体（IGF-1R）水平； 4. 测试随机接受 DPP 生活方式干预的 PCa 患者是否在干预结束后至少 6 个月内维持生活方式的改变 时期。 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。随着人们越来越认识到许多患有 PCa 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危险因素，以降低这些男性的疾病进展速度。这项研究的结果可能对改善诊断为临床局限性 PCa 的男性的整体结果和疾病特异性结果具有广泛的影响，并提供积极生活方式的治疗替代方案 用于主动监视。