Effect and Mechanism of Acupuncture for Cancer-related Cognitive Impairment (ENHANCE)

针灸治疗癌症相关认知障碍（ENHANCE）的效果和机制

• 批准号: 10403490
• 负责人: JUN J MAO
• 金额: $ 71.88万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10403490
• 关键词: Acupuncture Therapy; Address; Affect; Animal Model; Biological Markers; Biometry; Brain-Derived Neurotrophic Factor; Breast Cancer Patient; Breast Cancer survivor; Breast Oncology; Cancer Center; Cancer Control; Cancer Survivor; Chinese; Chinese Traditional Medicine; Clinical Trials; Cognition; Cognitive; Cognitive Therapy; Cognitive aging; Comorbid Insomnia; Data; Etiology; Evaluation; Exercise; Grant; Hippocampus (Brain); Individual; Intervention; Intervention Studies; Knowledge; Long-Term Effects; Longterm Follow-up; Malignant Neoplasms; Measures; Memory; Methodology; Modeling; Needles; Neurocognitive; Oncology Nurse; Patients; Phenotype; Pilot Projects; Process; Public Health; Publishing; Quality of life; Randomized; Reporting; Research; Role; Sample Size; Science; Scientific Advances and Accomplishments; Serum; Severities; Sleep; Sleep disturbances; Sleeplessness; Symptoms; Techniques; Testing; Therapeutic; Time; United States; Verbal Learning; Waiting Lists; Work; Yoga; arm; attentional control; base; cancer prevention; cancer-related cognitive impairment; chemotherapy; cognitive function; cognitive rehabilitation; cognitive training; comparative effectiveness trial; design; efficacious treatment; evidence base; executive function; experience; improved; mindfulness; multidisciplinary; novel; personalized medicine; primary endpoint; primary outcome; programs; recruit; response; secondary analysis; secondary outcome; skills; symptom management; treatment as usual; trial comparing; Acupuncture Therapy; Address; Affect; Animal Model; Biological Markers; Biometry; Brain-Derived Neurotrophic Factor; Breast Cancer Patient; Breast Cancer survivor; Breast Oncology; Cancer Center; Cancer Control; Cancer Survivor; Chinese; Chinese Traditional Medicine; Clinical Trials; Cognition; Cognitive; Cognitive Therapy; Cognitive aging; Comorbid Insomnia; Data; Etiology; Evaluation; Exercise; Grant; Hippocampus (Brain); Individual; Intervention; Intervention Studies; Knowledge; Long-Term Effects; Longterm Follow-up; Malignant Neoplasms; Measures; Memory; Methodology; Modeling; Needles; Neurocognitive; Oncology Nurse; Patients; Phenotype; Pilot Projects; Process; Public Health; Publishing; Quality of life; Randomized; Reporting; Research; Role; Sample Size; Science; Scientific Advances and Accomplishments; Serum; Severities; Sleep; Sleep disturbances; Sleeplessness; Symptoms; Techniques; Testing; Therapeutic; Time; United States; Verbal Learning; Waiting Lists; Work; Yoga; arm; attentional control; base; cancer prevention; cancer-related cognitive impairment; chemotherapy; cognitive function; cognitive rehabilitation; cognitive training; comparative effectiveness trial; design; efficacious treatment; evidence base; executive function; experience; improved; mindfulness; multidisciplinary; novel; personalized medicine; primary endpoint; primary outcome; programs; recruit; response; secondary analysis; secondary outcome; skills; symptom management; treatment as usual; trial comparing

PROJECT SUMMARY Cancer-related cognitive impairment (CRCI) is a devastating condition, affecting 3 in 4 breast cancer survivors. Non-pharmacologic interventions (e.g. exercise, cognitive training) demonstrated preliminary effects for CRCI, but their specific efficacies need to be confirmed in larger, rigorous trials using active/attention controls. More importantly, given the multi-faceted etiology and presentation of CRCI, it is unlikely that a single therapy is optimal for all patients; thus, there remains a critical need to test novel interventions and personalize treatment. Acupuncture has a growing evidence base in cancer symptom management, but its role in treating CRCI remains unclear. In animal models, acupuncture has been shown to modulate hippocampal expression of brain-derived neurotrophic factor (BDNF), an important cognitive biomarker. A Chinese study (N=80) found that acupuncture improved cognitive function and increased serum BDNF in breast cancer patients compared to usual care, but findings were limited by small sample size and lack of sham control, thus precluding evaluation of specific efficacy. In secondary analyses of our recent comparative effectiveness trial (N=160) of acupuncture versus cognitive-behavioral therapy for insomnia (CBT-I), acupuncture significantly improved subjective insomnia as well as perceived and objective cognitive functions, suggesting that targeting sleep improves cognition. Acupuncture also significantly increased serum BDNF, particularly among those with low baseline levels, whereas CBT-I did not. This suggests that BDNF is a specific mechanism by which acupuncture influences cognition and could help to identify individuals most likely to respond to acupuncture, thereby personalizing therapy. Based on this data, our central hypothesis is that acupuncture is an efficacious treatment for CRCI that works through a mechanism involving BDNF and sleep. Building on this work, we bring together a multi-disciplinary team to propose the Effect and Mechanism of Acupuncture for Cancer-related Cognitive Impairment (ENHANCE) trial. We found that nearly 80% of breast cancer survivors with CRCI report insomnia, echoing the growing research on connections between cognition and sleep. Thus, we will recruit 260 breast cancer survivors with CRCI and insomnia and randomize them to one of 3 conditions in an RCT: 1) acupuncture, 2) sham acupuncture (SA), or 3) usual-care wait-list control (WLC). We will collect serum BDNF and patient-reported/objective measures of cognition and sleep from baseline to Week 26. The Specific Aims are 1) to determine the effects of acupuncture on perceived CRCI and objective cognitive function; 2) to evaluate the mechanism of acupuncture on perceived CRCI and objective cognitive function via BDNF; and 3) to elucidate the role of insomnia on perceived CRCI and objective cognitive function in context of acupuncture. If successful, our study would expand treatment options for CRCI, advance mechanistic understanding of acupuncture, and disentangle the relationship between sleep and cognition, helping to shift the treatment paradigm towards a personalized model that targets CRCI phenotypes based on BDNF profile and insomnia.

项目摘要 与癌症相关的认知障碍（CRCI）是一种毁灭性的疾病，影响了四分之三的乳腺癌幸存者。 非药物干预措施（例如运动，认知训练）对CRCI表现出初步影响， 但是，在使用主动/注意力控制的更大，严格的试验中，需要确认它们的特定效率。更多的 重要的是，鉴于CRCI的多方面病因和表现，单一疗法不可能 最适合所有患者；因此，仍然需要测试新干预措施和个性化治疗方法。 针灸在癌症症状管理方面具有越来越多的证据基础，但其在治疗CRCI中的作用 仍然不清楚。在动物模型中，针灸已被证明可以调节 脑衍生的神经营养因子（BDNF），一种重要的认知生物标志物。中文研究（n = 80） 该针灸改善了乳腺癌患者的认知功能和血清BDNF的增加 在通常的护理中，但发现受到小样本量和缺乏假控制的限制，因此排除了 评估特定功效。在我们最近的比较有效性试验（n = 160）的次要分析中 针灸与虚假的认知行为疗法（CBT-I），针灸显着改善 主观失眠以及感知和客观的认知功能，表明针对睡眠 改善认知。针灸还显着增加了血清BDNF，特别是在低 基线水平，而CBT-I没有。这表明BDNF是一种特定的机制 针灸会影响认知，并有助于确定最有可能对针灸做出反应的个人 从而个性化疗法。基于这些数据，我们的中心假设是针灸是有效的 通过涉及BDNF和睡眠的机制来工作的CRCI治疗。在这项工作的基础上，我们带来 一个多学科团队共同提出针灸对癌症相关的效果和机制 认知障碍（增强）试验。我们发现近80％的乳腺癌幸存者有CRCI报告 失眠，回应了对认知与睡眠之间联系的日益研究。因此，我们将招募260 患有CRCI和失眠的乳腺癌幸存者，并将其随机为RCT中的3个条件之一：1） 针灸，2）假针刺（SA）或3）通常的护理列表控制（WLC）。我们将收集血清BDNF 从基线到第26周，患者报告的认知和睡眠措施。具体目的 是1）确定针灸对感知的CRCI和客观认知功能的影响； 2）到 通过BDNF评估针灸对感知的CRCI和客观认知功能的机制； 3） 为了阐明失眠对针灸的感知CRCI和客观认知功能的作用。 如果成功，我们的研究将扩大CRCI的治疗方案，提高机械理解 针灸，并解开睡眠与认知之间的关系，有助于改变治疗 针对基于BDNF概况和失眠症的CRCI表型的个性化模型的范式。