Interventions for Cognitive Impairment in Colorectal Cancer Patients

结直肠癌患者认知障碍的干预措施

• 批准号: 8879608
• 负责人: Michelle C Janelsins
• 金额: $ 20.03万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8879608
• 关键词: Address; Adjuvant Chemotherapy; Adult; Aerobic; Aftercare; Analysis of Covariance; Anti-Inflammatory Agents; Anti-inflammatory; Area; Attention; Attention Concentration; Biological Assay; CCL2 gene; Cancer Patient; Clinical; Clinical Trials; Cognition; Cognition Disorders; Cognitive; Colorectal Cancer; Cytokine Receptors; Data; Dose; Education; Enzyme-Linked Immunosorbent Assay; Etiology; Exercise; Goals; Health education; Home environment; IL8 gene; Ibuprofen; Impaired cognition; Individual; Inflammation; Inflammatory; Interleukin-10; Interleukin-6; Intervention; Intervention Studies; Link; Measures; Mediating; Memory; Nerve Degeneration; Neurodegenerative Disorders; Neuropsychological Tests; Oral; Paper; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Phase III Clinical Trials; Pilot Projects; Placebos; Population; Preparation; Public Health; Quality of life; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Reporting; Research; Resistance; Risk; Role; Serum; Survivors; TNF gene; Testing; Time; Trail Making Test; Verbal Learning; Visual; Walking; Work; arm; base; cancer therapy; capsule; chemobrain; chemotherapy; cognitive function; colon cancer patients; computerized; cytokine; design; effective therapy; executive function; experience; improved; innovation; intervention effect; malignant breast neoplasm; neuropsychological; novel; programs; public health relevance; satisfaction; strength training; trial comparing; visual memory

 DESCRIPTION (provided by applicant): A majority of colorectal cancer patients (78%), as demonstrated by our research and the research of others, experience chemotherapy-related cognitive impairment (CRCI); however, interventions to address CRCI in this population are lacking. Main problem areas include difficulty in memory, concentration, attention and executive function. CRCI impairs many facets of quality of life; these effects can last for years in up to 35% of survivors. The etiology of CRCI is not clearly understood, and there are no effective management approaches. Our preliminary work, and that of others, has shown that chemotherapy increases proinflammatory cytokines and that these changes are linked with cognitive impairments in cancer patients during chemotherapy, suggesting that inflammation may contribute to CRCI. If so, interventions that reduce inflammation might alleviate CRCI. Ibuprofen targets many of the same inflammatory cytokine pathways found to be increased in cancer patients, and it can delay the onset or reduce the effects of cognitive impairments in healthy individuals as well as in those at risk for cognitive diseases. Evidence suggests that exercise, which also reduces inflammation, can improve cognitive functioning in healthy adults, in patients with neurodegenerative disease, and those at risk for cognitive decline. Very preliminary research suggests exercise may improve CRCI in cancer patients. Reduction of inflammation with exercise and low-dose ibuprofen is a promising target to alleviate CRCI, particularly during chemotherapy; however, this hypothesis has not yet been tested in colorectal cancer patients. In preparation for this proposal, we conducted a small feasibility randomized clinical trial of an exercise intervention (aerobic and resistance training) and low-dose ibuprofen (200 mg twice daily) for 6 weeks in colorectal cancer patients receiving chemotherapy and showed that both of these interventions are feasible, patients can complete all measures, and that the study evokes high satisfaction. Pilot results from this study suggest that both interventions independently are promising for alleviating CRCI. This innovative R21 proposal builds upon our feasibility trial and includes a three-arm randomized controlled clinical trial comparing the influence of ibuprofen + health education (Arm 1), placebo + exercise (Arm 2) and placebo + health education (control; Arm 3) on CRCI in 84 colorectal cancer patients undergoing adjuvant chemotherapy and experiencing CRCI. The exercise and ibuprofen arms will each be compared to the control (Arm 3) with the primary goal of assessing the preliminary efficacy of each intervention for alleviating CRCI in colorectal cancer patients receiving chemotherapy. We are also assessing whether these interventions influence levels of cytokines and receptors, and whether intervention effects are mediated by inflammation. The study proposal herein is designed to provide critical preliminary information and data to inform an anticipated R01. This study would be one of the first, if not the first, clinical trial to assess interventions for CRCI in colorectal cancer patiets receiving chemotherapy. The benefit of improving CRCI as a result of this study could be considerable.

 描述（由申请人提供）：正如我们的研究和其他人的研究所证明的那样，大多数结直肠癌患者（78％）都会经历化疗相关的认知障碍（CRCI），但是，缺乏针对该人群的 CRCI 的干预措施；主要问题领域包括记忆力、注意力、注意力和执行功能方面的困难；这些影响可能会在高达 35% 的幸存者中持续数年。CRCI 的病因尚不清楚。我们和其他人的初步工作表明，化疗会增加促炎细胞因子，并且这些变化与化疗期间癌症患者的认知障碍有关，这表明炎症可能会导致 CRCI。因此，减少炎症的干预措施可能会减轻 CRCI 的靶点，这些炎症细胞因子途径与癌症患者中增加的炎症细胞因子途径相同，并且它可以延缓健康个体以及高危人群的认知障碍的发作或减轻其影响。有证据表明，对于认知疾病。运动还可以减少炎症，可以改善健康成年人、神经退行性疾病患者和有认知能力下降风险的人的认知功能。非常初步的研究表明，运动可以改善癌症患者的 CRCI。布洛芬是缓解 CRCI 的一个有希望的靶点，特别是在化疗期间；然而，这一假设尚未在结直肠癌患者中得到检验。为了准备该提案，我们进行了一项运动干预（有氧训练和阻力训练）的小型可行性随机临床试验。 ） 和小剂量布洛芬 （200 mg，每天两次）在接受化疗的结直肠癌患者中进行 6 周，结果表明这两种干预措施都是可行的，患者可以完成所有措施，并且该研究引起了很高的满意度，该研究的试点结果表明这两种干预措施独立有效。这项创新的 R21 提案基于我们的可行性试验，包括一项三组随机对照临床试验，比较布洛芬 + 健康教育（第 1 组）、安慰剂 + 运动（第 2 组）和安慰剂 + 健康的影响。对 84 名接受辅助化疗并经历 CRCI 的结直肠癌患者进行 CRCI 教育（对照组；第 3 组），将运动组和布洛芬组与对照组（第 3 组）进行比较，主要目标是评估每种干预措施的初步疗效。我们还在评估这些干预措施是否会影响细胞因子和受体的水平，以及干预效果是否是由炎症介导的。本文的研究提案旨在提供重要的初步信息和数据。告知预期的 R01 研究将是其中之一。 第一个（如果不是第一个的话）临床试验评估对接受治疗的结直肠癌患者的 CRCI 干预措施 这项研究对改善 CRCI 的益处可能是相当大的。