A Combination Therapy to Treat Cancer-Related Fatigue

项目摘要 癌症相关性疲劳（CRF）是前列腺癌患者最常见的症状， 根治性治疗-放疗（RT）和雄激素剥夺治疗（ADT）期间和之后的患者，以及 对患者的身体、心理、社会、职业功能和整体素质产生不利影响 然而，目前的治疗方案不能令人满意地缓解CRF。练习（EX）和 哌醋甲酯（MP）是迄今为止研究最多和最有益的CRF治疗方法，但两者都只有 适度的影响。根据初步数据表明，EX + MP的组合是可行的， 有效地减少CRF，拟议的研究将解决指导性假设， 使用随机安慰剂对照试验，加MP将导致更稳健的疲劳改善。的 主要目的是确定EX + MP联合治疗是否上级EX+安慰剂 前列腺癌患者接受放疗和雄激素剥夺治疗的CRF 12周（目标1）。CRF将使用功能曲线中的曲线下面积（AUC）进行测量。 慢性疾病治疗-疲劳评估（FACIT-F）子量表，以检验联合用药 与运动加安慰剂相比，EX加MP可导致CRF的更大降低。解决 假设EX + MP组合将导致其他CRF相关指标的改善， EX + MP对生活质量的影响（使用癌症治疗功能评估-一般）， 睡眠障碍（使用匹兹堡睡眠质量指数和多维疲劳症状 清单），睡眠/清醒时间活动（活动记录），焦虑和抑郁情绪（使用医院焦虑和 抑郁量表）、身体功能（使用通常的步态速度、30秒椅子站立试验和握力 强度）、心肺适应性（最大摄氧量）、炎症（C反应蛋白）和认知指标将 评估（目标2）。为了解决哌醋甲酯加运动的组合将 具有协同效应，其超过单独运动或单独哌醋甲酯对CRF的降低， EX和MP的潜在协同作用将通过测量所有四个组中的FACIT-FAUC来评价， 从而告知EX和MP如何一起交互的模型（目标3）。最后，大脑活动的差异 EX + MP干预的应答者和非应答者之间的差异将使用 脑电图（EEG）（目的4），以确定CRF的新生物标志物，并为新模型提供信息 根据执行局和/或《蒙特利尔议定书》，整合通用报告格式及其各个方面。创新利用现有 技术，结合针对特定和明确定义的患者人群的CRF新方法， 可以为CRF的安全，可行和有效的治疗提供证据，并将产生新的，高度的 CRF上可解释的数据构成了理解和治疗疲劳的重要一步。

PROJECT SUMMARY Cancer-related fatigue (CRF) is the most frequent and debilitating symptom experienced by prostate cancer patients during and after curative treatment-radiotherapy (RT) and androgen deprivation therapy (ADT), and has detrimental effects on patients' physical, psychological, social, occupational functioning and overall quality of life; however, current treatment options fail to satisfactorily alleviate CRF. Exercise (EX) and Methylphenidate (MP) are by far the most investigated and beneficial therapies for CRF, but both have only modest effects. Based on preliminary data suggesting that the combination of EX plus MP is feasible and may be efficacious in reducing CRF, the proposed research will address the guiding hypothesis that combining EX plus MP will result in a more robust improvement of fatigue using a randomized placebo-controlled trial. The primary objective is to determine if the combination of EX + MP is superior to EX plus placebo in the treatment of CRF in patients with prostate cancer scheduled to receive radiotherapy with androgen deprivation therapy for 12 weeks (Aim 1). CRF will be measured using the area under the curve (AUC) in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale to test the hypothesis that the combination of EX plus MP will result in a greater reduction of CRF compared with exercise plus placebo. To address the hypothesis that the combination of EX plus MP will result in improvements in additional CRF-related measures, the effects of EX plus MP on quality-of-life (using the Functional Assessment of Cancer Therapy – General), sleep disturbance (using the Pittsburgh Sleep Quality Index and the Multidimensional Fatigue Symptom Inventory), sleep/wake time activity (actigraphy), anxiety and depressed mood (using the Hospital Anxiety and Depression Scale), physical function (using usual gait speed, the 30-second chair stand test, and hand grip strength), cardiorespiratory fitness (VO2 max), inflammation (C-reactive protein), and cognitive measures will be assessed (Aim 2). To address the hypothesis that the combination of methylphenidate plus exercise will have synergistic effects that exceed the reduction in CRF by either exercise alone or methylphenidate alone, potential synergistic effects of EX and MP will be evaluated by measuring the FACIT-F AUC in all four arms, thus informing a model of how EX and MP may interact together (Aim 3). Finally, differences in brain activity between responders and non-responders to the EX plus MP intervention will be explored using electroencephalography (EEG) (Aim 4) in order to identify novel biomarkers of CRF and to inform a new model integrating underlying CRF and its dimensions in response to EX and/or MP. The innovative use of existing technologies, combined with a novel approach to CRF targeting a specific and well-defined patient population, could provide evidence for a safe, feasible, and effective treatment for CRF, and will yield new and highly interpretable data on CRF constituting a significant step forward in the understanding and treatment of fatigue.