A Combination Therapy to Treat Cancer-Related Fatigue

治疗癌症相关疲劳的联合疗法

基本信息

批准号：
10308673
负责人：
Sriram Yennu
金额：
$ 47.58万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-12-01 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10308673
关键词：
Address Anxiety Area Under Curve Biological Markers Brain C-reactive protein Cancer Etiology Cancer Intervention Cancer Patient Chronic Disease Cognition Cognitive Combined Modality Therapy Data Depressed mood Development Digit structure Dimensions Disease Distress Double-Blind Method Electroencephalography Equipment and supply inventories Etiology Exercise Fatigue Fostering Gait speed Goals Hand Hand Strength Hospitals Individual Inflammation Intervention Level of Evidence Malignant Neoplasms Malignant neoplasm of prostate Measures Mental Depression Modality Modeling Moods Nature Neuraxis Occupational Outcome Measure Patients Pharmacology Study Physical Function Pittsburgh Sleep Quality Index Placebo Control Placebos Population Prevalence Public Health Quality of life Radiation Radiation therapy Randomized Regimen Research Research Design Risk Ritalin Safety Schedule Secondary to Severities Sleep Sleep disturbances Stretching Symptoms Technology Testing Time Treatment-Related Cancer VO2max actigraphy androgen deprivation therapy arm base cancer biomarkers cancer diagnosis cancer risk cancer therapy cancer type cardiorespiratory fitness clinical care compliance behavior cost curative treatments design disabling symptom effective therapy experience improved innovation insight novel marker novel strategies patient population placebo group psychologic psychological distress randomized controlled design randomized controlled study randomized placebo controlled trial responders and non-responders response social standard care

项目摘要

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.

项目概要癌症相关疲劳 (CRF) 是前列腺癌最常见、最令人衰弱的症状治疗期间和之后的患者——放射治疗（RT）和雄激素剥夺治疗（ADT），以及对患者的身体、心理、社会、职业功能和综合素质有影响然而，目前的治疗方案未能令人满意地缓解 CRF 和运动 (EX)。哌醋甲酯 (MP) 是迄今为止研究最多且有益的 CRF 治疗方法，但两者都仅具有初步数据表明 EX 加 MP 的组合是可行的，并且可能会产生适度的效果。为了有效降低 CRF，拟议的研究将解决结合 EX 的指导假设使用随机安慰剂对照试验，加上 MP 将更有效地改善疲劳。主要目标是确定 EX + MP 组合在治疗中是否优于 EX 加安慰剂计划接受雄激素剥夺疗法放疗的前列腺癌患者的 CRF 发生情况持续 12 周（目标 1）将使用功能曲线下面积 (AUC) 进行测量。慢性病治疗疲劳评估 (FACIT-F) 子量表检验以下假设：与运动加安慰剂相比，EX 加 MP 会导致 CRF 更大程度地降低。假设 EX 加 MP 的组合将导致额外 CRF 相关措施的改进， EX 加 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库存）、睡眠/醒来时间活动（体动记录仪）、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 秒椅子站立测试和握力力量）、心肺健康（最大摄氧量）、炎症（C 反应蛋白）和认知测量将进行评估（目标 2）。具有超过单独运动或单独哌醋甲酯降低 CRF 的协同效应， EX 和 MP 的潜在协同效应将通过测量所有四个组中的 FACIT-F AUC 来评估，从而告知模型 EX 和 MP 如何相互作用（目标 3）。将使用以下方法探讨对 EX 加 MP 干预措施的响应者和非响应者之间的差异脑电图 (EEG)（目标 4），以识别 CRF 的新型生物标志物并为新模型提供信息底层整合 CRF 及其维度，以响应 EX 和/或 MP 的创新使用。技术，结合针对特定且明确定义的患者群体的 CRF 新颖方法，可以为 CRF 的安全、可行、有效的治疗提供证据，并将产生新的、高度 CRF 的可解释数据构成了理解和治疗疲劳的重要一步。