Yoga Versus CBT-I for Insomnia in Cancer Survivors and Biobehavioral Mechanisms

摘要： 高达90%的癌症幸存者报告在治疗后失眠或某种形式的睡眠质量损害(SQI) 与昼夜节律失调、身体功能受损、慢性上调共同发生 炎症反应，当病情严重时，增加癌症发病率和死亡率。尽管随处可见 失眠和SQI，在癌症幸存者中被低估了诊断和治疗。瑜伽是一种广为人知的运动 运动干预，具有改善失眠和SQI疗效的有希望的初步证据。我们的 对来自12个社区的410名癌症幸存者进行的先前多中心III期随机对照试验(RCT) 美国的肿瘤学实践表明，我们的标准化瑜伽干预(YOCAS(C)(R)：4周、2x/周、75周 Min/Sess)对失眠和SQI有中等到很大的改善，同时也改善了昼夜节律 活动节律。瑜伽参与者也减少了，而对照组参与者增加了睡眠药物的使用。 YOCAS(C)(R)的依从性良好(80%)，没有与研究相关的不良事件，100%的参与者 发现YOCAS(C)(R)有用，并将其推荐给其他幸存者。下一个符合逻辑的经验步骤，符合 NCI的研究重点是为幸存者开发有效的、基于证据的支持性护理干预措施， 将YOCAS(C)(R)干预与黄金标准治疗(即，认知行为疗法)进行比较 失眠[CBT-I])和时间和注意力安慰剂对照。因此，我们建议进行一项 多中心，三臂，盲法，第三阶段随机对照试验，比较ARM的效果1)我们的YOCAS(C)(R)计划，ARM 2) CBT-I和ARM 3)对630名癌症幸存者进行6-12个月后失眠的健康教育对照 使用有效措施和分析技术进行辅助治疗。YOCAS(C)(R)和CBT-I将于 使用标准有效临床形式的组(即，YOCAS(C)(R)=2x/wk，在4周内75分钟疗程； CBT-I 1x/wk，在8周内进行90分钟的治疗)。健康教育也将以小组形式和 与YOCAS(C)(R)匹配的时间和注意力相等。我们将要求参与者满足DSM-IV失眠症 失眠严重程度指数(ISI)上的失眠标准和临床分界值，评估3-和 失眠益处的6个月可持续性，并检查可能的基于概念的生物学机制 (昼夜活动节律、身体功能和炎症)，可能通过YOCAS(C)(R)影响失眠。 我们假设YOCAS(C)(R)将与CBT-I一样有效，并且在改善方面比健康教育更有效 失眠、SQI、昼夜活动节律、身体功能和炎症；失眠的改善将是 在YOCAS(C)(R)和CBT-I组持续3个月和6个月，而在健康教育组不持续； 昼夜活动节律、身体功能和炎症的变化将调节YOCAS(C)(R)的作用 治疗失眠。这是第一阶段III，盲法随机对照试验，以测试：1)YOCAS(C)(R)与 CBT-I和改善失眠和SQI的健康教育对照，2)3个月和6个月的可持续性 失眠得益于YOCAS(C)(R)，以及3)特定生物介质在YOCAS疗效中的作用。 (C)(R)

ABSTRACT: Up to 90% of cancer survivors report insomnia or some form of sleep quality impairment (SQI) post-treatment which co-occurs with dysregulated circadian rhythm, impaired physical function, chronically up-regulated inflammatory responses, and, when severe, increased cancer morbidity and mortality. Despite the ubiquity of insomnia and SQI, they are under-diagnosed and under-treated in cancer survivors. Yoga is a well-tolerated exercise intervention with promising preliminary evidence for its efficacy in improving insomnia and SQI. Our previous multicenter, phase III, randomized, controlled, trial (RCT) in 410 cancer survivors from 12 community oncology practices in the U.S., showed that our standardized yoga intervention (YOCAS(c)(R): 4 wks, 2x/wk, 75 min/sess) produced moderate to large improvements in insomnia and SQI while also improving circadian activity rhythms. Yoga participants also decreased, while control participants increased, sleep medication use. Adherence to YOCAS(c)(R) was good (80%) with no study-related adverse events, and 100% of participants found YOCAS(c)(R) useful and would recommend it to other survivors. The next logical empirical steps, in line with NCI research priorities to develop effective, evidence-based, supportive care interventions for survivors, are to compare the YOCAS(c)(R) intervention to a gold-standard treatment (i.e., Cognitive Behavioral Therapy for Insomnia [CBT-I]) and a time and attention placebo control. Therefore, we propose to conduct a multicenter, 3-arm, blinded, phase III RCT comparing the effect of Arm 1) our YOCAS(c)(R) program, Arm 2) CBT-I, and Arm 3) a health education control on insomnia in 630 cancer survivors 6-12 months following adjuvant treatment using valid measures and analytical techniques. YOCAS(c)(R) and CBT-I will be delivered in groups using standard effective clinical formats (i.e., YOCAS(c)(R) = 2x/wk in 75-minute sessions over 4 weeks; CBT-I 1x/wk in 90-minute sessions over 8 weeks). Health education will also be delivered in groups and matched for equal time and attention to YOCAS(c)(R). We will require participants to meet DSM-IV insomnia criteria and the clinical cut off score for insomnia of >10 on the Insomnia Severity Index (ISI), assess the 3- and 6-month sustainability of insomnia benefits, and examine possible conceptually based biological mechanisms (circadian activity rhythms, physical function, and inflammation) that may influence insomnia via YOCAS(c)(R). We hypothesize YOCAS(c)(R) will be as effective as CBT-I and more effective than health education for improving insomnia, SQI, circadian activity rhythms, physical function, and inflammation; insomnia improvements will be sustained 3 and 6 months later in the YOCAS(c)(R) and CBT-I groups but not in the health education group; and changes in circadian activity rhythms, physical function, and inflammation will mediate the effects of YOCAS(c)(R) on insomnia. This is the first phase III, blinded RCT to test: 1) the effectiveness of YOCAS(c)(R) compared to CBT-I and a health education control for improving insomnia and SQI, 2) the 3- and 6-month sustainability of insomnia benefits from YOCAS(c)(R), and 3) the role of specific biological mediators in the efficacy of YOCAS . (c)(R)