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.

项目摘要 疲劳是癌症患者经历的最普遍，最令人痛苦的症状之一。治疗 与癌症相关的疲劳的选择有限；其他疗法是研究的重点。安非他酮 自1999年以来，已被确定为癌症相关疲劳的潜在疗法。安非他酮具有多种作用 该靶向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）轴的功能。细胞色素P 450 B6（CYP2B6）对安非他酮的代谢已是 广泛的表征。两项对安非他酮的试点研究表明，有望减少癌症相关 疲劳，但迄今为止尚未进行足够的随机对照试验。目标的目标 当前的研究是进行第一次足够的，随机的，双盲的，安慰剂对照试验 与癌症相关疲劳的安非他酮。由于疲劳在乳腺癌女性中已经很好地表征了 该研究将集中在这一人群上。 422例完成的无病乳腺癌患者的样本 化学疗法和/或放疗12-60个月，并报告将招募严重的疲劳 通过罗切斯特大学癌症中心（URCC）国家癌症研究所肿瘤学 研究计划（NCORP）。参与者将被随机分配1：1，以接收通用的安非他酮XL或安慰剂。 疲劳将在随机进行之前和12周后评估。血液和唾液将被收集到 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 功能）。数据将用于解决以下目的：1）确定安非他酮的功效 安慰剂减少双盲，安慰剂对照的随机临床试验的疲劳 疲劳的幸存者； 2）评估安非他酮在疲劳中乳腺癌幸存者的耐受性，3） 探索安非他酮对癌症相关疲劳的假定机制的影响，4）探索 CYP2B6基因型与安非他酮代谢和疲劳变化的关联。来自 当前的研究可能会彻底改变与癌症相关的疲劳的治疗，因为安非他酮是安全，廉价的， 与当前有限的治疗相比，许多患者的可耐受性和可接受性可能更广泛，可以接受 选项。探索安非他酮对癌症相关疲劳的假定机制的影响可能打开 新的途径，用于其他有效治疗。探索功效的遗传主持人可以帮助 确定哪些患者最有可能受益和量身定制剂量。