Clinical trial NCT05353322: Breaking Up Prolonged Sedentary Behavior to Improve Cardiometabolic Health
Official title: Breaking Up Prolonged Sedentary Behavior to Improve Cardiometabolic Health: an Adaptive Dose-Finding Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sedentary Behavior
Cardiometabolic Risk Factors
Blood Pressure
Glucose
Keywords: Sedentary Behavior
Physical Activity
Blood Pressure
Glucose
Insulin
Dose-finding
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2022-04-29
Enrollment: 324
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: The purpose of this Phase 1 research study is to answer two questions: (1) How frequent should periods of prolonged sedentary time be interrupted? and (2) What is the appropriate duration or length of time of these breaks in sedentary time? To address these questions, this project will conduct a state-of-the-art adaptive dose finding study under controlled laboratory conditions to determine the minimally effective dose (the smallest dose) that yields cardiometabolic benefit for two separate sedentary break elements (frequency and duration). Study findings will ultimately determine how often and for how long people should break up periods of prolonged sedentary time to transiently improve established cardiovascular risk factors; key foundational information critical to the success of future long-term trials and ultimately public health guidelines.

Primary Aim: To determine the minimally effective dose combination(s) of frequency and duration needed to provide cardiometabolic benefit during an 8-hour experimentation period. Specifically, the study will determine:

1a. For each fixed duration, the minimum sedentary break frequency (e.g., every 30 min, 60 min, 120 min) that demonstrates a reduction in systolic BP, diastolic BP, or glucose compared with a sedentary control condition.

1b. For each fixed frequency, the minimum sedentary break duration (e.g., activity breaks of 1 min, 5 min, 10 min) that demonstrates a reduction in systolic BP, diastolic BP, or glucose compared with a sedentary control.

Secondary Aim: It is also critical to public health strategy to assess the acceptability/feasibility of various sedentary break doses as too high a dose will yield poor uptake. To address this need, the maximally tolerated dose (the highest dose that does not cause undue physical/psychological distress) for frequency and duration of sedentary breaks will also be determined via assessment of 4 constructs: physical exhaustion/fatigue, affect (e.g., mood, emotion), tolerability (e.g., completion of dose protocol), and safety (e.g., hypoglycemia). Maximally tolerated dose will be defined as the highest dose where \<20% of participants exhibit an adverse outcome.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 18 years of age or older
* Ability to read, write and speak English or Spanish
* No chronic medical conditions \[examples include but not limited to: CVD, diabetes, high blood pressure/hypertension, chronic obstructive pulmonary disease (COPD), HIV/AIDS\]
* Do not take medication (over-the-counter or herbal) to control blood pressure (such as an antihypertensive medication) or glucose (such as a diabetes control medication)
* Do not currently smoke cigarettes
* No pre-existing musculoskeletal conditions (including but not limited to osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis) that would prevent participation in intermittent physical activity
* No allergies to common food allergens including wheat, eggs, milk or other dairy, gluten, fructose, peanuts or other nuts
* No dietary restrictions such as vegan, gluten free, halal
* Good peripheral veins with high possibility of getting IV access

Exclusion Criteria:

* Unable to provide consent

Primary outcomes:
measure: Change in Systolic Blood Pressure from Baseline
timeFrame: Baseline, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 7.5 hours, 8 hours
measure: Change in Diastolic Blood Pressure from Baseline
timeFrame: Baseline, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 7.5 hours, 8 hours
measure: Net Glucose Incremental Area Under the Curve
timeFrame: Every 15 minutes over 8-hour trial visit
Secondary outcomes:
measure: Proportion of participants that fully completed the sedentary break protocol.
timeFrame: Immediately after completion of experimental (activity break) trial visit (up to 8 hours)
measure: Proportion of participants with hypoglycemia
timeFrame: Baseline, 0.5 hour, 1 hour, 3 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours, 8 hours
measure: Proportion of participants with an exaggerated blood pressure response
timeFrame: Baseline, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 7.5 hours, 8 hours
measure: Proportion of participants in whom a musculoskeletal injury was observed/reported.
timeFrame: End of experimental (activity break) trial visit (up to 8 hours)
measure: Proportion of participants reporting physical exhaustion score greater than or equal to 9
timeFrame: Baseline, 4 hours, 8 hours
measure: Proportion of participants reporting Feeling Scale Score less than 0
timeFrame: Up to 8 hours
measure: Blood Insulin Area Under the Curve
timeFrame: Baseline, 0.5 hour, 1 hour, 3 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours, 8 hours
measure: Blood Glucose Area Under the Curve
timeFrame: Baseline, 0.5 hour, 1 hour, 3 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours, 8 hours
Other outcomes:
measure: Utrecht Work Engagement Scale (UWES-9) Score
timeFrame: 4 hours, 8 hours
measure: Work Performance Score
timeFrame: 4 hours, 8 hours
Locations:
city: New York
country: United States
facility: Center for Behavioral Cardiovascular Health
state: New York
Study officials:
affiliation: Florence Irving Assistant Professor of Behavioral Medicine, CUIMC
name: Keith Diaz, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Professor of Biostatistics, Department of Biostatistics, CUIMC
name: Ying Kuen (Ken) Cheung, PhD
role: STUDY_CHAIR
References: