Sleep Apnea Treatment with Positive Airway Pressure for Prevention of Diabetes Mellitus

通过气道正压通气治疗睡眠呼吸暂停以预防糖尿病

• 批准号: 9789866
• 负责人: Naresh M Punjabi
• 金额: $ 39.87万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-25 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789866
• 关键词: Adherence; Adult; Adverse effects; Applications Grants; Attenuated; Beta Cell; Bioethics; Biological Assay; Biometry; Blood Glucose; Blood Pressure; Body Weight decreased; Body Weights and Measures; C-reactive protein; Cells; Central obesity; Clinical Research; Clinical Trials; Complex; Data; Data Analyses; Data Coordinating Center; Data Quality; Development; Diabetes Mellitus; Diabetes prevention; Diagnostic; Endocrinology; Ensure; Epidemiology; Equipoise; Ethics; Glycosylated hemoglobin A; Goals; Grant; Health Care Costs; Home environment; Homeostasis; Hypoxemia; Impairment; Incidence; Institution; Institutional Review Boards; Insulin Resistance; Interleukin-6; Intervention; Laboratories; Leadership; Life Expectancy; Lung; Manuals; Medicine; Metabolic; Metabolism; Methodology; Methods; Microvascular Dysfunction; Minnesota; Modeling; Multi-Institutional Clinical Trial; Multicenter Trials; NIH Program Announcements; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Obstructive Sleep Apnea; Onset of illness; Outcome; Oxidative Stress; Pathogenesis; Pennsylvania; Phase; Population; Prediabetes syndrome; Predisposition; Prevalence; Preventive service; Protocols documentation; Psychology; Public Health Schools; Publications; Quality of life; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Reading; Research; Research Personnel; Rest; Risk Factors; Role; Sampling; Sleep; Sleep Apnea Syndromes; Sleep Fragmentations; Source; Sympathetic Nervous System; Symptoms; System; Talents; Testing; Time; Training; Universities; arm; clinical research site; common treatment; data management; diabetes prevention program; efficacy trial; eligible participant; experience; glucose metabolism; high risk; human subject; indexing; inflammatory marker; innovation; insulin secretion; insulin sensitivity; intervention program; lifestyle intervention; macrovascular disease; multidisciplinary; operation; organizational structure; preservation; pressure; prevent; programs; quality assurance; randomized trial; response; screening; sound; trial design; waist circumference; weight loss intervention; weight loss program

ABSTRACT This application is in response to the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) program announcement PAR-18-423 for implementing a multi-center randomized clinical trial to test the hypothesis that treatment of obstructive sleep apnea (OSA) with positive airway pressure (PAP) therapy in people with prediabetes will reduce the progression to type 2 diabetes mellitus (T2DM). For the U34 planning phase, we have established a network of ten clinical sites guided by an experienced team of investigators with an extensive background in conducting multicenter randomized trials. To provide leadership for the trial, we have built a consortium of exceptional investigators and include the following: (a) The Center for Clinical Trials at the Johns Hopkins University Bloomberg School of Public Health to establish a central Data Coordinating Center; (b) The Clinical Research Center for Sleep at the University of Pennsylvania to organize a Sleep Reading Center for home sleep testing; (c) a PAP adherence core; (d) a weight loss core at Brown University; and (e) a bioassay core laboratory at the University of Minnesota. In this application, we describe our record of conducting and managing multi-center research programs; strategies for assembling and managing a complex research network; and the talented team of coinvestigators with expertise in pulmonary and sleep medicine, endocrinology, clinical trials methodology, weight loss interventions, epidemiology, and biostatistics. The Specific Aims for the U34 planning period are to: (1) refine the organizational structure and the leadership plan for the trial; (2) finalize the study protocol and associated source documents, provide clinical site training, and develop a manual of operations for the Sleep Reading Center, the PAP Adherence Core, and the Clinical Sites; (3) construct a data management system, establish methods of data quality assurance, and develop a manual of operations for the DCC; (4) outline plans for data analysis and handling of study-related publications and presentations; and (5) obtain human subjects and regulatory approvals from a central IRB. The U34 consortium will develop a U01 grant application for a multi-center clinical trial on the utility of PAP therapy in preventing T2DM in people with OSA and prediabetes. The Specific Aims of the U01 trial are as follows. Aim 1: To determine whether, in people with prediabetes and moderate-to-severe OSA, the addition of PAP therapy to a lifestyle intervention is associated with lower rate of progression from prediabetes to T2DM. Aim 2: To assess whether, in people with prediabetes and moderate-to-severe OSA, the addition of PAP therapy to a lifestyle intervention program is associated with greater improvements than with lifestyle intervention alone in: (a) insulin sensitivity, as assessed by the homeostasis model assessment index (HOMA-IR); (b) hemoglobin A1c modeled as a continuous variable; (c) sympathetic nervous system activity; (d) inflammatory markers including C-reactive protein (CRP) and interleukin-6 (IL-6); (e) resting blood pressure; (f) body weight and measures of central obesity (i.e., waist circumference); and (g) OSA-related symptoms and quality of life.

摘要 此应用程序是为了响应美国国立糖尿病、消化和肾脏疾病研究所（NIDDK） 计划公告PAR-18-423，用于实施多中心随机临床试验， 气道正压通气治疗阻塞性睡眠呼吸暂停（OSA） 患有前驱糖尿病的人将减少向2型糖尿病（T2 DM）的进展。关于U34规划 在第一阶段，我们建立了一个由十个临床研究中心组成的网络，由经验丰富的研究人员团队指导， 进行多中心随机试验的广泛背景。为了领导审判，我们 建立了一个由杰出的研究人员组成的联盟，其中包括：（a）临床试验中心， 约翰霍普金斯大学彭博公共卫生学院建立中央数据协调中心; (b)宾夕法尼亚大学睡眠临床研究中心将组织一个睡眠阅读中心 用于家庭睡眠测试;（c）PAP坚持核心;（d）布朗大学的减肥核心;以及（e）生物测定 明尼苏达大学的核心实验室。在本申请中，我们描述了我们的记录， 管理多中心研究项目;组装和管理复杂研究网络的策略; 以及在肺部和睡眠医学，内分泌学，临床 试验方法学、减肥干预、流行病学和生物统计学。U34的具体目标 规划期间的主要任务是：（1）完善审判组织结构和领导方案;（2）确定 研究方案和相关源文件，提供临床研究中心培训，并制定 操作的睡眠阅读中心，PAP坚持核心，和临床网站;（3）构建一个数据 管理系统，建立数据质量保证方法，并制定 DCC;（4）概述数据分析和处理研究相关出版物和演示文稿的计划;以及（5） 从中心IRB获得人类受试者和监管批准。U34联盟将开发U 01 一项关于PAP治疗在预防T2 DM患者中的效用的多中心临床试验的资助申请 OSA和前驱糖尿病U 01试验的具体目的如下。目标1：确定是否在人 对于糖尿病前期和中重度OSA患者，在生活方式干预的基础上增加PAP治疗， 与糖尿病前期进展为T2 DM的速率较低相关。目的2：评估是否，在人与 糖尿病前期和中度至重度OSA患者，在生活方式干预计划中加入PAP治疗， 与单独的生活方式干预相比，在以下方面有更大的改善：（a）胰岛素敏感性， 通过稳态模型评估指数（HOMA-IR）;（B）血红蛋白A1 c建模为连续变量; (c)交感神经系统活性;（d）炎性标志物，包括C-反应蛋白（CRP）和 白细胞介素-6（IL-6）;（e）静息血压;（f）体重和向心性肥胖的测量（即，腰 （g）OSA相关症状和生活质量。