Breaking up prolonged sedentary behavior to improve cardiometabolic health (BREAK2): protocol for a dose-finding adaptive randomization trial

BACKGROUND: Excessive sedentary behavior is highly prevalent in developed nations and is a risk factor for cardiovascular disease (CVD) morbidity and mortality. 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 effective and tolerated sedentary break doses. The objective of the proposed study is to determine the minimally effective dose (e.g., the lowest dose) for two elements of a sedentary break (frequency and duration) that yields improvements in established CVD risk factors. 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 will also be determined. METHODS: This study is a randomized crossover trial conducted under laboratory conditions among 324 adults without chronic medical conditions. Participants complete two trial conditions (8 h each), a sedentary break (intervention) condition and an uninterrupted sitting (control) condition, in a randomized order. The sedentary break condition consists of 1 of 25 possible frequency/duration combinations (e.g. walk every 30 min for 5 min), selected according to a Bayesian adaptive randomization method. Primary outcomes used to inform the adaptive randomization are glucose and blood pressure serially assessed over each trial condition. Constructs of dose toxicity (tolerability, safety, physical exhaustion/fatigue, and affect) are also serially assessed. DISCUSSION: This study will elucidate the minimally effective and maximally tolerated frequency and duration of a sedentary break that yields improvements in established CVD risk factors, information important for the development of quantitative sedentary behavior guidelines. TRIAL REGISTRATION: This trial has been registered with the Clinical Trials Registry maintained by the National Library of Medicine at the National Institutes of Health on April 29, 2022. The registration ID is NCT05353322.