2/2 Cognitive Behavioral Therapy and Trazodone Effects on Sleep and Blood Pressure in Insomnia Phenotypes Based on Objective Sleep Duration: A Sequential Cohort/Randomized Controlled Trial

2/2 认知行为疗法和曲唑酮对基于客观睡眠持续时间的失眠表型的睡眠和血压的影响：一项序贯队列/随机对照试验

• 批准号: 10581992
• 负责人: Wendy C King
• 金额: $ 44.59万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10581992
• 关键词: Adult; Age; Blood Pressure; Cardiovascular system; Characteristics; Classification; Clinical; Clinical Trials; Cognitive Therapy; Cohort Studies; Collaborations; Communication; Data; Data Coordinating Center; Decision Making; Disease; Disease remission; Double-Blind Method; Down-Regulation; Drug Prescriptions; Electrocardiogram; Ensure; Evidence based treatment; Functional disorder; Funding; Genetic; Goals; Guidelines; Health; Health Care Costs; Home Blood Pressure Monitoring; Hydrocortisone; Hypertension; Impairment; Individual; Knowledge; Laboratories; Measures; Mediating; Mental Health; Metabolic; Monitor; Occupational Health; Outcome; Participant; Patient Self-Report; Patients; Pharmaceutical Preparations; Phenotype; Physiological; Physiology; Placebo Control; Placebos; Polysomnography; Preparation; Process; Protocols documentation; Publications; Quebec; Randomized; Randomized, Controlled Trials; Recommendation; Recording of previous events; Research Design; Research Personnel; Risk; Salivary; Sampling; Severities; Site; Sleep; Sleeplessness; Statistical Data Interpretation; Symptoms; Testing; Time; Training; Trazodone; United States National Institutes of Health; Validity and Reliability; actigraphy; base; blind; blood pressure elevation; blood pressure reduction; cardiovascular disorder risk; clinical phenotype; clinical practice; clinical research site; cohort; comparative efficacy; data management; data sharing; efficacy evaluation; hypothalamic-pituitary-adrenal axis; improved; indexing; off-label use; post intervention; precision medicine; predicting response; primary outcome; protocol development; randomized placebo controlled trial; recruit; response; secondary outcome; sex; side effect; treatment effect; treatment guidelines; treatment response

Insomnia is a prevalent health problem associated with adverse cardiovascular, metabolic, and mental health outcomes. Previously proposed subtypes, based on traditional clinical measures, have poor reliability and validity and have not proven useful for guiding insomnia treatment decisions. Based on a large base of preliminary data from various domains and several investigative groups, we have identified a particular phenotype, insomnia with short sleep duration (ISS), that is associated with increased risk for adverse health outcomes, greater physiological hyperarousal as indicated by hypothalamic-pituitary-adrenal (HPA) axis activation, and worse response to Cognitive-Behavioral Treatment for Insomnia (CBT-I). The proposed study represents the next logical extension of our previous observations: To determine the efficacy of CBT-I in individuals with ISS vs. Insomnia with normal sleep duration (INS) among adults with elevated blood pressure (BP), and to examine the efficacy of trazodone among non-remitters to CBT-I. CBT-I is recommended as first-line treatment for insomnia, and trazodone is a widely-prescribed but grossly understudied medication for insomnia. In addition, our pilot data demonstrate differential efficacy of CBT-I and trazodone in ISS and INS: trazodone, but not CBT-I, increases objective total sleep time (TST), and lowers BP and evening cortisol in ISS. We will conduct a 4-site cohort study followed by a placebo-controlled RCT in 600 adults (≥18y) with insomnia. The cohort study will examine the efficacy of CBT-l among individuals with ISS vs. INS phenotypes (n=300 each), defined by polysomnographic (PSG) TST. The subsequent RCT will compare the efficacy of trazodone vs. placebo among CBT-I non-remitters. Investigators at the 4 study sites (Hershey, Denver, Pittsburg, and Quebec) have a long history of collaboration and successful completion of NIH-funded mechanistic and clinical trial studies. Our primary outcome will be the insomnia remission at 8 weeks, defined as Insomnia Severity Index (ISI) <8; ISI is the gold-standard self-report measure of insomnia symptoms. Secondary outcomes will include ISI (continuous), objective (i.e., PSG and actigraphy) measures of sleep efficiency (in the CBT-I cohort study) and TST, HBP, and evening cortisol (in the trazodone-placebo RCT). In exploratory analyses, we will test whether changes in evening cortisol mediate the effect of trazodone on objective TST and HBP. Outcomes will be assessed at 8 weeks and 6 months following the end of treatment to evaluate the durability of treatment effects. Demonstrating a differential efficacy of CBT-I as a function of insomnia phenotype would aid the goals of precision medicine, which directs therapy on the basis of clinical phenotypes and physiology as well as genetics. Although CBT-I is recommended as first-line treatment for all adults with insomnia, finding a worse response in the ISS phenotype will lead to reconsidering this current guideline in lieu of matching patients' phenotype to treatment. Demonstrating the efficacy of trazodone among CBT-I non-remitters will fill an obvious and important knowledge gap in insomnia treatment l as it pertains to its current wide-spread off-label use.

失眠是一种普遍的健康问题，与不利的心血管、代谢和心理健康有关