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: 10394730
• 负责人: HEATHER S.L. JIM
• 金额: $ 59.04万
• 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 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10394730
• 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; Placebo Control; 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.

项目总结 疲劳是癌症患者最普遍和最痛苦的症状之一。治疗 治疗癌症相关性疲劳的选择有限；其他治疗方法是研究的高度优先事项。安非他酮 自1999年以来一直被确定为治疗癌症相关疲劳的一种潜在疗法。安非他酮有多种作用 靶向与癌症相关的疲劳的通路，包括炎症和下丘脑脑垂体炎 肾上腺(HPA)轴功能。细胞色素P450 B6对安非他酮的代谢 具有广泛的特征。安非他酮的两项初步研究显示，它有望减少与癌症相关的疾病 疲劳，但到目前为止还没有进行动力充足的随机对照试验。的目标是 目前的研究是进行第一个充分有效、随机、双盲、安慰剂对照的试验 用于治疗癌症相关疲劳的安非他酮。因为疲倦是乳腺癌女性的显著特征， 这项研究将重点放在这一人群上。完成调查的422名无病乳腺癌患者样本 化疗和/或放射治疗前12-60个月，并报告严重疲劳将被招募 通过罗切斯特大学癌症中心(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的随机比例接受非专利安非他酮XL或安慰剂治疗。 疲劳将在随机化之前和12周后进行评估。血液和唾液将被收集到 测量安非他酮代谢物、炎症、CYP2B6基因和皮质醇(HPA轴的标记物 功能)。数据将被用来解决以下目标：1)确定安非他酮与 安慰剂在乳腺癌双盲、安慰剂对照、随机临床试验中减轻疲劳的作用 疲劳症幸存者；2)评估乳腺癌疲劳症幸存者对安非他酮的耐受性；3) 探索安非他酮对癌症相关性疲劳的可能机制的影响，以及4)探索 CYP2B6基因与安非他酮代谢和疲劳改变的关系。积极的结果来自 目前的研究可能会给癌症相关性疲劳的治疗带来革命性的变化，因为安非他酮是安全、廉价的， 可广泛获得，而且可能比目前的有限治疗更容易被许多患者耐受和接受 选择。探讨安非他酮对癌症相关性疲劳的可能机制的影响 寻找其他有效治疗方法的新途径。探索疗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，并量身定制剂量。