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. The investigator 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 the aims, the investigator 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. The study 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.

This project is 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 Phase I/II study will provide key foundational evidence critical to the success of future Phase III and Phase IV randomized trials and ultimately public health guidelines.