Clinical trial NCT04469790: Effects of Multi-day Interruptions in Sitting on Type 2 Diabetes-relevant Outcomes in Children
Official title: Testing the Efficacy of Multi-day Interruptions in Sedentary Behaviors on Metabolic, Cognitive, and Affective Outcomes in Youth at Risk for Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sedentary Behavior
Affect
Metabolic Disturbance
Anxiety
Cardiac Autonomic Nervous System Function
Keywords: exercise
cognitive functions
continuous glucose monitoring
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
First posted: 2020-07-14
Enrollment: 188
Sex: ALL
Minimum age (years): 8
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized parallel-arm clinical trial
Primary purpose: PREVENTION

Brief summary: The overall objective of this in-lab randomized controlled trial is to test the efficacy of multi-day interruptions in sedentary behavior vs. single bouts of sustained exercise on metabolic, cognitive, affective, and cardiac autonomic nervous system responses in children with overweight and obesity who are at risk for type 2 diabetes. The use of continuous glucose monitoring will provide insight into the daily and cumulative metabolic effects of each condition that have thus far not been studied. In-lab studies demonstrating sustained efficacy of this approach in ameliorating negative effects of sedentary behaviors in children are necessary for the optimization of field-based interventions. Given the lack of success of interventions to prevent obesity-related diseases and increasing rates of type 2 diabetes in children and its related healthcare costs, this study addresses a critical public health need by testing of novel intervention strategies to reduce obesity-related diseases in children with overweight and obesity.

Detailed description: Rationale: Sedentary behavior (SB) contributes to increased risk for obesity and metabolic disease, cognitive deficits, affect disorders, and cardiovascular disease over the lifespan. These are critical outcomes because children with these risk factors are more likely to develop type 2 diabetes mellitus (T2DM). SB increases T2DM risk by promoting hyperglycemia and greater postprandial glycemic variability as well as via cognitive detriments and depressive symptoms that lead to poor energy balance behaviors, obesity, and worsening insulin resistance. Additionally, prolonged SB may contribute to dominance of the sympathetic nervous system and lead to poor cardiovascular disease outcomes. Physical activity can reduce these risk factors, however less than half of US youth meet guideline recommendations, and physical activity continues to decline throughout adolescence. Thus, there is a critical need to test alternative intervention approaches to sustained bouts of exercise for the prevention of T2DM in children. The investigators were the first to show that interrupting SB with short, 3-minute, bouts of moderate exercise improved glucose tolerance and negative mood in a single 3-hour session. However, it is unknown whether these short-term improvements translate to sustained multi-day benefits to metabolic, cognitive, mood, and cardiac autonomic nervous system outcomes.

Intervention: This phase II randomized controlled trial (RCT) will compare the effects of SB interruptions vs. sustained bouts of exercise to prolonged sitting in 8-11-year-old children with overweight/obesity. Participants (N=150 (50 per group)) will be recruited from the community. The participants will wear continuous glucose monitors for one week and complete pre- and post- experiment 3-hour oral glucose tolerance tests (OGTT). Children will be randomized to 7 consecutive days of one of the following 3-hour experimental conditions: a) continuous sitting (SIT); b) sitting interrupted by 3-minute bouts of moderate-intensity walking every 30 minutes (SIT+WALK); or c) a single 18-minute bout of moderate-intensity walking followed by continuous sitting (EX).

Objectives/Purpose: The overall goal of this study is to test the efficacy of multi-day effects of interrupting SB as a T2DM prevention strategy in youth with overweight/obesity. This proposal will address the following aims: (1) determine the multi-day efficacy of interrupting sitting on glucose homeostasis measured by continuous glucose monitor and oral glucose tolerance tests; (2) determine the multi-day efficacy of interrupting sitting on cognitive function improvements; (3) determine the multi-day efficacy of interrupting sitting on affect and anxiety improvements; and (4) determine the multi-day efficacy of interrupting sitting on cardiac autonomic nervous system improvements measured by heart rate variability.

Study Population: The study population will consist of children with overweight/obesity recruited from the greater Los Angeles area. Children will be screened for eligibility (no evidence of type 2 diabetes, have overweight/obesity, be in good health, and be in early pubertal stages).

Study Methodology: This study is a phase II RCT with 3 study arms. Participants (N=150) will complete one screening visit to determine eligibility, complete a fitness test, and body composition analysis via dual x-ray absorptiometry (DEXA). All participants will complete two 3-hour in-lab oral glucose tolerance tests (spaced 6 days apart). Participants will wear an activity monitor on the right thigh and an electrocardiogram (ECG) monitor on the chest 7 days to determine baseline activity levels and heart rate variability, respectively. Then, participants will complete 7 consecutive in-lab sessions (SIT, SIT+WALK, or EX), with a 3-hour OGTT on Days 1 and 7. Participants will wear activity monitors, continuous glucose monitors, and ECG monitors during these 7 days of experimental sessions. Questionnaires will assess dietary intake, affect, anxiety, and mood, and the NIH Toolbox will assess executive cognitive function.

Study Arms: Participants will be randomized to 7 consecutive days of one of the following 3-hour experimental conditions in the lab: a) continuous sitting (SIT); b) sitting interrupted by 3-minute bouts of moderate-intensity walking every 30 minutes (SIT+WALK); or c) a single 18-minute bout of moderate-intensity walking followed by continuous sitting (EX).

Endpoints/Outcomes: The primary endpoints are: insulin, C-peptide, and glucose area under the curve (AUC) in the in-lab experiments, and glucose AUC from the continuous glucose monitor. Secondary endpoints are positive and negative affect, anxiety, executive cognitive function, and heart rate variability metrics.

Follow-up: Study duration is estimated as 14 days minimum and 30 days maximum, to allow for a 7-21 day period between the screening and experimental visits.

Statistical Analyses: The populations for analyses include the full analytical dataset which consists of all randomized study participants; the investigators will employ per protocol and intent to treat analyses.

Eligibility criteria: Inclusion Criteria:

1. Age 8-11 years-old
2. Good general health
3. BMI≥85th percentile

Exclusion Criteria:

1. Significant cardiac or pulmonary disease likely to or resulting in hypoxia or decreased perfusion
2. Diagnosis of T2DM and/or presence of other endocrinologic disorders leading to obesity (e.g., Cushing Syndrome)
3. Current or past anti-psychotic drug use that would affect metabolism
4. Non-diet treatment for hypertension or dyslipidemia
5. Precocious puberty and/or receiving androgen and estrogen therapy
6. Medication use known to affect body composition/weight

Primary outcomes:
measure: In-Lab glucose area under the curve (AUC)
timeFrame: 3 hours (-10, 0, 30, 60, 90, 120, 150, 180 minutes) AUC change from Day 1 to Day 7
measure: In-Lab insulin area under the curve (AUC)
timeFrame: 3 hours (-10, 0, 30, 60, 90, 120, 150, 180 minutes) AUC change from Day 1 to Day 7
measure: In-Lab c-peptide area under the curve (AUC)
timeFrame: 3 hours (-10, 0, 30, 60, 90, 120, 150, 180 minutes) AUC change from Day 1 to Day 7
measure: Continuous glucose monitor measures
timeFrame: 7 days
Secondary outcomes:
measure: Cognitive function measures
timeFrame: change from Day 1 to Day 7
measure: Positive and Negative Affect Scale for Children
timeFrame: change from Day 1 to Day 7
measure: State-Trait Anxiety Inventory for Children (STAIC)
timeFrame: change from Day 1 to Day 7
measure: Cardiac autonomic nervous system measures
timeFrame: 7 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Britni Ryan Belcher, PhD, MPH
state: California
Study officials:
References:
citation: Belcher BR, Berrigan D, Papachristopoulou A, Brady SM, Bernstein SB, Brychta RJ, Hattenbach JD, Tigner IL Jr, Courville AB, Drinkard BE, Smith KP, Rosing DR, Wolters PL, Chen KY, Yanovski JA. Effects of Interrupting Children's Sedentary Behaviors With Activity on Metabolic Function: A Randomized Trial. J Clin Endocrinol Metab. 2015 Oct;100(10):3735-43. doi: 10.1210/jc.2015-2803. Epub 2015 Aug 27.
citation: Broadney MM, Belcher BR, Berrigan DA, Brychta RJ, Tigner IL Jr, Shareef F, Papachristopoulou A, Hattenbach JD, Davis EK, Brady SM, Bernstein SB, Courville AB, Drinkard BE, Smith KP, Rosing DR, Wolters PL, Chen KY, Yanovski JA. Effects of Interrupting Sedentary Behavior With Short Bouts of Moderate Physical Activity on Glucose Tolerance in Children With Overweight and Obesity: A Randomized Crossover Trial. Diabetes Care. 2018 Oct;41(10):2220-2228. doi: 10.2337/dc18-0774. Epub 2018 Aug 6.