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 炎症反应，并且当严重时，增加癌症发病率和死亡率。尽管无处不在， 失眠和SQI，他们在癌症幸存者中诊断不足和治疗不足。瑜伽是一种很好的耐受性 运动干预具有改善失眠和SQI的有效性的初步证据。我们 既往在来自12个社区的410名癌症幸存者中进行的多中心、III期、随机、对照试验（RCT） 美国的肿瘤学实践，显示我们的标准化瑜伽干预（YOCAS（c）（R）：4周，2次/周，75 min/sess）对失眠和SQI产生了中度至较大的改善，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。 对YOCAS（c）（R）的依从性良好（80%），无研究相关不良事件，100%的参与者 发现YOCAS（c）（R）很有用，并将推荐给其他幸存者。接下来的逻辑经验步骤， 与NCI的研究重点，为幸存者制定有效的，以证据为基础的支持性护理干预措施， 将YOCAS（c）（R）干预与金标准治疗进行比较（即，认知行为治疗 Inhibition [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、3组、设盲、III期RCT，比较了第1组我们的YOCAS（c）（R）项目，第2组） CBT-I和第3组）630名癌症幸存者6-12个月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 使用标准有效临床格式的组（即，YOCAS（c）（R）= 2次/周，75分钟，持续4周; CBT-I 1x/wk，90分钟，持续8周）。健康教育亦会以小组形式进行， 匹配相同的时间和注意力的YOCAS（C）（R）。我们将要求参与者满足DSM-IV失眠 标准和失眠严重程度指数（ISI）>10的失眠临床截止评分，评估3-和 6-一个月的持续性失眠的好处，并检查可能的概念为基础的生物机制 （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，并且比健康教育更有效地改善 失眠，SQI，昼夜活动节律，身体功能和炎症;失眠的改善将是 YOCAS（c）（R）和CBT-I组在3个月和6个月后持续存在，而健康教育组则没有; 昼夜活动节律、身体功能和炎症的变化将介导YOCAS（c）（R）的作用 关于失眠症这是第一个III期盲法随机对照试验：1）与对照组相比， CBT-I和健康教育控制改善失眠和SQI，2）3个月和6个月的持续性， 失眠受益于YOCAS（c）（R），以及3）特定生物介质在YOCAS功效中的作用。 （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)