Breaking up Prolonged Sedentary Behavior to Improve Cardiometabolic Health: An Adaptive Dose-Finding Study

打破长时间久坐行为以改善心脏代谢健康：一项适应性剂量探索研究

• 批准号: 10401933
• 负责人: Ken Cheung
• 金额: $ 75.57万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-05 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10401933
• 关键词: Address; Adult; Advisory Committees; Advocate; Affect; American; American Heart Association; Behavioral trial; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Cohort Studies; Data; Developed Countries; Development; Diastolic blood pressure; Dose; Effectiveness; Elements; Emotions; Epidemic; Exhibits; Fatigue; Foundations; Frequencies; Future; Glucose; Guidelines; Health; Health Benefit; Hour; Hypoglycemia; Interruption; Intervention; Laboratories; Link; Maximum Tolerated Dose; Measures; Methods; Moods; Morbidity - disease rate; Outcome; Participant; Performance; Persons; Phase; Physical activity; Plant Roots; Process; Protocols documentation; Public Health; Randomized; Randomized Controlled Trials; Recommendation; Reporting; Research; Risk; Risk Factors; Safety; Smoking; Standardization; Strenuous Exercise; Suggestion; Testing; Time; Visit; Walking; Work; adverse outcome; base; cardiometabolism; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular risk factor; control trial; dose information; energy balance; evidence base; evidence based guidelines; exhaustion; experimental study; improved; innovation; mortality; phrases; psychological distress; randomized trial; recruit; sedentary; sedentary lifestyle; success; therapy development; uptake; vigorous intensity

Excessive sedentary behavior is highly prevalent in developed nations and is a risk factor for cardiovascular disease (CVD) morbidity and mortality. Evidence suggests sedentary behavior is not simply a form of inactivity that elicits positive energy balance. Instead sedentary behavior itself may be harmful. As such, health agencies have provided general recommendations to “sit less, move more” by interspersing brief periods of activity. However, a lack of empirical evidence describing how often (e.g. every 30 min, every 60 min) and for how long (e.g. 1 min activity bouts, 5 min activity bouts) sedentary time should be interrupted (a “sedentary break”) to yield health benefit has precluded more quantitative, actionable guidelines. To date, rigorous and methodical dose escalation experiments have not been conducted to elucidate efficacious and tolerated sedentary break doses. Without specific targets to provide to the public; public health initiatives targeting sedentary behavior will likely have minimal effectiveness. Critically, without rigorously tested dosing information; randomized controlled trials targeting sedentary behavior may be fruitless; bearing risk of inefficacious or intolerable doses. The objective of the proposed study is to determine the minimally effective dose (e.g. the smallest dose) for two elements of a sedentary break, frequency and duration, that yields improvements in established CVD risk factors. We will also determine the maximally tolerated dose (e.g. the highest dose that does not cause undue physical/psychological distress) for both frequency and duration of sedentary breaks. To address our aims, we will conduct a state-of-the-art dose finding study under well controlled laboratory conditions using an innovative Bayesian adaptive randomization method for dose determination never before applied to behavioral trials. This method will enable us to efficiently test 25 possible frequency/duration combinations in just a single study. We will recruit 324 adults to complete a total of 2 trial conditions in the laboratory (8 hours each), namely a sedentary break (active) condition and an uninterrupted sitting (control) condition, in a randomized order. The sedentary break condition will consist of 1 of 25 possible frequency/duration combinations (e.g. every 30 min for 10 min), selected according to the adaptive randomization protocol. Established CVD risk factors, including blood pressure and glucose, as well as measures of dose tolerability (physical exhaustion/fatigue, affect) and work engagement and performance will be serially assessed during each trial. We view this project as a groundbreaking step towards developing evidence-based guidelines for sedentary behavior that will establish a foundation upon which a successful sedentary behavior intervention development process can be rooted. By identifying the minimally effective and maximally tolerated dose combinations for the frequency and duration of a sedentary break; this study will provide key foundational evidence critical to the success of future Phase III and Phase IV randomized trials and ultimately public health guidelines.

过度久坐行为在发达国家非常普遍，是心血管疾病的危险因素 疾病（CVD）发病率和死亡率。有证据表明久坐行为不仅仅是不活动的一种形式 从而引发正能量平衡。相反，久坐行为本身可能有害。因此，卫生机构 通过穿插短暂的活动时间，提出了“少坐、多动”的一般建议。 然而，缺乏描述频率（例如每 30 分钟、每 60 分钟）和持续时间的经验证据 （例如 1 分钟活动时间、5 分钟活动时间）应中断久坐时间（“久坐休息”） 产量健康效益排除了更定量、可操作的指导方针。迄今为止，严谨、有条理 尚未进行剂量递增实验来阐明有效且可耐受的久坐休息 剂量。没有向公众提供具体目标；针对久坐行为的公共卫生举措将 可能效果甚微。至关重要的是，没有经过严格测试的剂量信息；随机对照 针对久坐行为的试验可能不会有结果；承担无效或无法耐受剂量的风险。这 拟议研究的目的是确定两种药物的最低有效剂量（例如最小剂量） 久坐休息、频率和持续时间等要素，可改善已确定的 CVD 风险 因素。我们还将确定最大耐受剂量（例如，不会引起不当反应的最高剂量） 身体/心理困扰），包括久坐休息的频率和持续时间。为了实现我们的目标，我们 将使用创新的方法在良好控制的实验室条件下进行最先进的剂量探索研究 用于确定剂量的贝叶斯自适应随机化方法以前从未应用于行为试验。这 方法将使我们能够在一项研究中有效地测试 25 种可能的频率/持续时间组合。我们 将招募324名成年人在实验室完成总共2个试验条件（每个8小时），即 久坐休息（活动）条件和不间断坐着（对照）条件，按随机顺序。这 久坐休息条件将包括 25 种可能的频率/持续时间组合中的一种（例如，每 30 分钟 10 分钟），根据自适应随机化协议进行选择。已确定的 CVD 危险因素，包括 血压和血糖，以及剂量耐受性的测量（身体疲惫/疲劳、情绪）和 每次试验期间将连续评估工作投入和绩效。我们将此项目视为 朝着制定基于证据的久坐行为指南迈出了开创性的一步，该指南将建立 成功的久坐行为干预开发过程可以在此基础上扎根。经过 确定针对频率和持续时间的最低有效剂量和最大耐受剂量组合 久坐休息；这项研究将为未来第三阶段的成功提供关键的基础证据 第四阶段随机试验和最终的公共卫生指南。