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: 10618959
• 负责人: JUN J MAO
• 金额: $ 70.86万
• 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/10618959
• 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; Discipline of Nursing; Etiology; Evaluation; Exercise; Grant; Hippocampus; Individual; Intervention; Intervention Studies; Knowledge; Long-Term Effects; Longterm Follow-up; Malignant Neoplasms; Measures; Memory; Methodology; Modeling; Needles; Neurocognitive; 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; 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; improvement on sleep; mindfulness; multidisciplinary; novel; personalized medicine; primary endpoint; primary outcome; programs; recruit; response; secondary analysis; secondary outcome; skills; symptom management; treatment as usual; trial comparing; verbal

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.

项目概要 癌症相关认知障碍 (CRCI) 是一种毁灭性的疾病，影响着四分之三的乳腺癌幸存者。 非药物干预措施（例如运动、认知训练）对 CRCI 表现出初步效果， 但它们的具体功效需要在使用主动/注意力控制的更大规模、严格的试验中得到证实。更多的 重要的是，考虑到 CRCI 的病因和表现是多方面的，单一疗法不太可能有效。 最适合所有患者；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 与针灸相比，针灸可改善乳腺癌患者的认知功能并增加血清 BDNF 常规护理，但研究结果受到样本量小和缺乏假控制的限制，因此排除了 评价具体疗效。在我们最近的比较有效性试验（N = 160）的二次分析中 针灸与认知行为疗法治疗失眠（CBT-I）相比，针灸显着改善 主观失眠以及感知和客观认知功能，表明以睡眠为目标 提高认知能力。针灸还显着增加血清 BDNF，特别是对于那些低水平的患者 基线水平，而 CBT-I 则没有。这表明 BDNF 是一种特定机制 针灸影响认知，有助于识别最有可能对针灸产生反应的个体， 从而实现个性化治疗。根据这些数据，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 和睡眠的机制发挥作用。在此工作的基础上，我们带来了 联合多学科团队提出针灸治疗癌症相关的效果和机制 认知障碍（ENHANCE）试验。我们发现近 80% 患有 CRCI 的乳腺癌幸存者 失眠，呼应了关于认知和睡眠之间联系的日益深入的研究。因此，我们将招募260名 患有 CRCI 和失眠的乳腺癌幸存者，并将他们随机分配到随机对照试验中的 3 种情况之一：1) 针灸，2) 假针灸 (SA)，或 3) 常规护理等候名单控制 (WLC)。我们将收集血清BDNF 从基线到第 26 周的患者报告/客观认知和睡眠测量。 具体目标 1) 确定针灸对感知 CRCI 和客观认知功能的影响； 2）到 通过BDNF评价针灸对感知CRCI和客观认知功能的机制；和 3) 阐明失眠对针灸背景下感知 CRCI 和客观认知功能的作用。 如果成功，我们的研究将扩大 CRCI 的治疗选择，推进对机制的理解 针灸，理清睡眠与认知之间的关系，有助于转变治疗方法 基于 BDNF 概况和失眠的针对 CRCI 表型的个性化模型的范式。

项目成果

Association of Perceived Benefit or Burden of Research Participation With Participants' Withdrawal From Cancer Clinical Trials.

• DOI: 10.1001/jamanetworkopen.2022.44412
• 发表时间: 2022-11-01
• 期刊: JAMA NETWORK OPEN
• 影响因子: 13.8
• 作者: Ulrich, Connie M.;Ratcliffe, Sarah J.;Zhou, Qiuping;Huang, Liming;Hochheimer, Camille;Gordon, Thomas;Knafl, Kathleen;Miller, Victoria;Naylor, Mary D.;Schapira, Marilyn M.;Richmond, Therese S.;Grady, Christine;Mao, Jun J.
• 通讯作者: Mao, Jun J.

Assessment of Oncology Patient Engagement and Interest in Virtual Mind-Body Programming: Moving Toward Personalization of Virtual Care.

评估肿瘤患者对虚拟身心编程的参与度和兴趣：走向虚拟护理的个性化。

• DOI: 10.1200/op.22.00424
• 发表时间: 2023
• 期刊: JCO oncology practice
• 影响因子: 4
• 作者: Hung,TonyKW;Latte-Naor,Shelly;Li,Yuelin;Kuperman,GiladJ;Seluzicki,Christina;Pendleton,Eva;Pfister,DavidG;Mao,JunJ
• 通讯作者: Mao,JunJ

Effect of acupuncture versus usual care on sleep quality in cancer survivors with chronic pain: Secondary analysis of a randomized clinical trial.

• DOI: 10.1002/cncr.34766
• 发表时间: 2023-07-01
• 期刊: CANCER
• 影响因子: 6.2
• 作者: Yang, Mingxiao;Baser, Raymond E.;Liou, Kevin T.;Li, Susan Q.;Piulson, Lauren;Panageas, Katherine S.;Mao, Jun J.
• 通讯作者: Mao, Jun J.

The relationship between anxiety and vaginal-related sexual health in postmenopausal breast cancer survivors on aromatase inhibitors therapies: a cross sectional study.

接受芳香酶抑制剂治疗的绝经后乳腺癌幸存者的焦虑与阴道相关性健康之间的关系：一项横断面研究。

• DOI: 10.1007/s10549-023-06981-5
• 发表时间: 2023
• 期刊: Breast cancer research and treatment
• 影响因子: 3.8
• 作者: Bryl,Karolina;Chimonas,Susan;Li,Xiaotong;Li,SusanQ;Mao,JunJ
• 通讯作者: Mao,JunJ

Yoga for cancer survivors with chemotherapy-induced peripheral neuropathy: Health-related quality of life outcomes.

• DOI: 10.1002/cam4.4098
• 发表时间: 2021-08
• 期刊: Cancer medicine
• 影响因子: 4
• 作者: Zhi WI;Baser RE;Zhi LM;Talukder D;Li QS;Paul T;Patterson C;Piulson L;Seluzicki C;Galantino ML;Bao T
• 通讯作者: Bao T