Randomized Placebo Controlled Trial of Bupropion for Cancer Related Fatigue

安非他酮治疗癌症相关疲劳的随机安慰剂对照试验

• 批准号: 10166792
• 负责人: HEATHER S.L. JIM
• 金额: $ 58.27万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-12 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10166792
• 关键词: Address; Adherence; Adopted; Affect; Aftercare; Alleles; Antidepressive Agents; Behavior Therapy; Biological; Blood; Breast Cancer Patient; Breast Cancer survivor; Bupropion; Cancer Center; Cancer Patient; Clinical Trials; Cognitive Therapy; Common Terminology Criteria for Adverse Events; Community Clinical Oncology Program; Cytochrome P450; Cytochromes; Data; Disease; Distress; Dopamine Uptake Inhibitors; Double-Blind Method; Exercise; Fatigue; Genes; Genetic; Genotype; Goals; Hydrocortisone; Incidence; Inflammation; Knowledge; Malignant Neoplasms; Measures; Mediating; Mental Depression; Metabolism; Modafinil; National Cancer Institute; Norepinephrine; Paroxetine; Participant; Pathway interactions; Patient Self-Report; Patients; Pharmacotherapy; Pilot Projects; Placebos; Population; Quality of life; Radiation therapy; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Reporting; Research; Research Priority; Ritalin; Saliva; Sampling; Selective Serotonin Reuptake Inhibitor; Sertraline; Sleeplessness; Survivors; Symptoms; TNF gene; Testing; Therapeutic Agents; Toxic effect; Treatment-Related Cancer; Universities; Variant; Woman; Work; cancer therapy; chemotherapy; dosage; double-blind placebo controlled trial; efficacious treatment; experience; hypothalamic-pituitary-adrenal axis; improved; malignant breast neoplasm; placebo group; programs; randomized placebo controlled trial; recruit

PROJECT SUMMARY Fatigue is one of the most prevalent and distressing symptoms experienced by cancer patients. Treatment options for cancer-related fatigue are limited; additional therapies are a high priority for research. Bupropion has been identified as a potential therapy for cancer-related fatigue since 1999. Bupropion has diverse actions that target pathways associated with cancer-related fatigue, including inflammation and hypothalamic pituitary adrenal (HPA) axis functioning. Metabolism of bupropion by cytochrome P 450 B6 (CYP2B6) has been extensively characterized. Two pilot studies of bupropion have shown promise in reducing cancer-related fatigue but to date no adequately-powered, randomized controlled trials have been conducted. The goal of the current study is to conduct the first adequately-powered, randomized, double-blinded, placebo-controlled trial of bupropion for cancer-related fatigue. Because fatigue is well-characterized in women with breast cancer, the study will focus on this population. A sample of 422 disease-free breast cancer patients who completed chemotherapy and/or radiotherapy 12-60 months previously and report significant fatigue will be recruited through the University of Rochester Cancer Center (URCC) National Cancer Institute Community Oncology Research Program (NCORP). Participants will be randomized 1:1 to receive generic bupropion XL or placebo. Fatigue will be assessed prior to randomization and 12 weeks later. Blood and saliva will be collected to measure bupropion metabolites, inflammation, CYP2B6 genotype, and cortisol (a marker for HPA axis functioning). Data will be used to address the following aims: 1) to determine the efficacy of bupropion versus placebo in reducing fatigue in a double-blinded, placebo-controlled, randomized clinical trial of breast cancer survivors with fatigue; 2) to assess the tolerability of bupropion in breast cancer survivors with fatigue, 3) to explore the effects of bupropion on putative mechanisms of cancer-related fatigue, and 4) to explore associations of CYP2B6 genotype with bupropion metabolism and changes in fatigue. Positive results from the current study could revolutionize the treatment of cancer-related fatigue, as bupropion is safe, inexpensive, widely-available, and may be more tolerable and acceptable for many patients than current, limited treatment options. Exploration of the effects of bupropion on putative mechanisms of cancer-related fatigue could open new avenues for additional efficacious treatments. Exploration of genetic moderators of efficacy could help identify which patients are most likely to benefit and tailor dosage.

项目概要 疲劳是癌症患者最普遍和最痛苦的症状之一。治疗 癌症相关疲劳的选择有限；额外的疗法是研究的重中之重。安非他酮 自 1999 年以来，安非他酮已被确定为治疗癌症相关疲劳的潜在疗法。安非他酮具有多种作用 针对与癌症相关疲劳相关的途径，包括炎症和下丘脑垂体 肾上腺 (HPA) 轴功能。安非他酮通过细胞色素 P 450 B6 (CYP2B6) 的代谢已被证实 广泛表征。安非他酮的两项试点研究显示出在减少癌症相关疾病方面的前景 疲劳，但迄今为止尚未进行足够有力的随机对照试验。的目标 目前的研究是进行第一个充分动力、随机、双盲、安慰剂对照试验 安非他酮用于治疗与癌症相关的疲劳。因为疲劳是乳腺癌女性的一个明显特征， 该研究将重点关注这一人群。 422 名无病乳腺癌患者的样本完成了 12-60 个月前接受过化疗和/或放疗并报告明显疲劳的患者将被招募 通过罗彻斯特大学癌症中心 (URCC) 国家癌症研究所社区肿瘤学 研究计划（NCORP）。参与者将以 1:1 的比例随机分配接受通用安非他酮 XL 或安慰剂。 将在随机分组前和 12 周后评估疲劳情况。血液和唾液将被收集以 测量安非他酮代谢物、炎症、CYP2B6 基因型和皮质醇（HPA 轴的标记物） 运作）。数据将用于实现以下目标：1) 确定安非他酮与 在乳腺癌双盲、安慰剂对照、随机临床试验中安慰剂可减轻疲劳 疲劳的幸存者； 2) 评估疲劳的乳腺癌幸存者对安非他酮的耐受性，3) 探索安非他酮对癌症相关疲劳的假定机制的影响，以及 4) 探索 CYP2B6 基因型与安非他酮代谢和疲劳变化的关联。积极的结果来自 目前的研究可能会彻底改变与癌症相关的疲劳的治疗，因为安非他酮安全、廉价， 广泛可用，并且对于许多患者来说比目前有限的治疗更容易耐受和接受 选项。探索安非他酮对癌症相关疲劳的推定机制的影响可能会开启 额外有效治疗的新途径。探索功效的遗传调节因素可能会有所帮助 确定哪些患者最有可能受益并调整剂量。