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

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 癌症相关的认知障碍（CRCI）是一种毁灭性的疾病，影响着四分之三的乳腺癌幸存者。 非药物干预（如运动、认知训练）对CRCI有初步效果， 但它们的具体功效需要在使用主动/注意力控制的更大、更严格的试验中得到证实。更 重要的是，考虑到CRCI的病因和表现的多方面性， 因此，仍然迫切需要测试新的干预措施和个性化治疗。 针灸在癌症症状管理方面有越来越多的证据基础，但其在治疗CRCI中的作用 仍不清楚在动物模型中，针灸已被证明可以调节海马的表达， 脑源性神经营养因子（BDNF），一种重要的认知生物标志物。一项中国研究（N=80）发现 针灸改善了乳腺癌患者的认知功能， 但由于样本量小和缺乏假手术对照，结果有限，因此排除了 具体疗效评价。在我们最近的比较有效性试验（N=160）的次要分析中， 针灸与认知行为疗法治疗失眠症（CBT-I）相比，针灸显著改善 主观失眠以及感知和客观认知功能，这表明针对睡眠 提高认知能力。针刺还显著增加了血清BDNF，特别是在那些低 基线水平，而CBT-I没有。这表明BDNF是一种特殊的机制， 针灸影响认知，可以帮助识别最有可能对针灸产生反应的个体， 从而使治疗个性化。基于这些数据，我们的中心假设是，针灸是一种有效的治疗方法。 CRCI的治疗通过涉及BDNF和睡眠的机制起作用。在此基础上，我们 联合多学科团队，提出针灸对肿瘤相关性的作用及机制 认知障碍（增强）试验。我们发现，近80%的乳腺癌幸存者与CRCI报告， 失眠症，呼应了越来越多的研究认知和睡眠之间的联系。因此，我们将招募260名 患有CRCI和失眠症的乳腺癌幸存者，并将其随机分配至RCT中的3种情况之一：1） 针灸，2）假针灸（SA），或3）常规护理等待名单对照（WLC）。我们将收集血清BDNF 以及从基线至第26周的患者报告/客观认知和睡眠测量。具体目标 1）确定针刺对感知CRCI和客观认知功能的影响; 2） 通过脑源性神经营养因子（BDNF）评价针刺对感知CRCI和客观认知功能的作用机制; 探讨失眠症在针刺环境下对认知反应认知能力和客观认知功能的影响。 如果成功，我们的研究将扩大CRCI的治疗选择，推进对CRCI机制的理解， 针灸，解开睡眠和认知之间的关系，有助于改变治疗方法， 这是一个基于BDNF谱和失眠症的个性化模型，靶向CRCI表型。