Impact of Meal Timing on Glycemic Profiles in Adolescents With Type 2 Diabetes

Study Overview
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Brief Summary
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Because of its simplicity, TLE may represent a more feasible approach for adolescents than other caloric restriction regimens based on macronutrient composition and kilocalories. Our preliminary data support TLE feasibility, acceptability, and safety in adolescents with obesity, with and without T2D. However, no trial to date has studied the effects of TLE on glycemic control and body composition in adolescents with T2D. Our long-term goal is to determine whether TLE is a beneficial as part of the medical regimen early in diagnosis in adolescents living with T2D, and if so, to identify: 1) participant characteristics associated with positive response, 2) mechanisms by which TLE operates, and 2) the best methods to administer TLE to maximally harness its effects. Therefore, the aim of this study will be to compare cardiometabolic effects of TLE (8-hr eating period/16-hr of daily fasting) versus a prolonged eating period (12+hour eating period) in a randomized pilot study with careful control of timely compliance, dietary composition, calorie intake, and physical activity to accurately capture the dosage of the intervention received. We hypothesize that TLE will minimize glycemic excursions, delay β-cell deterioration, and reduce body fat mass in adolescents with T2D when compared to prolonged eating periods. One-hundred adolescents with T2D will be recruited. All participants will be randomized to one of two meal-timing schedules to be followed for 12 weeks: (1) Control: >12-hour eating period or (2) TLE.

Detailed Description
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Intervention Design This is a prospective, pilot randomized controlled trial testing the efficacy of time-limited eating (TLE) on glycemic control, β-cell function, and body composition among predominantly Latinx adolescents with T2D compared to a prolonged eating period (12+hours). One-hundred adolescents with T2D will be recruited from CHLA. All participants will receive standard nutritional counseling and will be randomized to one of two meal-timing schedules to be followed for 12 weeks: (1) Control: 12-hour or more eating window without mealtime restrictions and (2) TLE: 8-hour eating period (16 hours of daily fasting). The implementation steps of the proposed RCT are as follows: The staff will introduce the study to all eligible participants either in person or virtually and consent interested families for the study. All participants and their families will complete baseline study surveys in REDcap. All participants and their families will receive training on the use and application of the Dexcom G6 CGM, which is FDA approved in patients 2 years and older. All equipment required for the duration of the study will be distributed to the participants in-person. Participants will receive enough sensors to wear the CGM daily for the entire study period. Participants will be instructed to change their sensor every 10 days with the assistance of the study staff. Each participant will be asked to download the CGM app onto their personal smartphone and set up an account with a pseudonym. All participants and their families will receive standard nutritional counseling and be randomized to one of two meal-timing schedules to be followed for 12 weeks: (1) Control: >12-hour eating or (2) TLE (8-hr eating period/16-hr of daily fasting). During the eating window, participants will not be required to count calories or monitor their food intake. Participants will choose and pay for their own food during the intervention. All participants will record their eating window daily and submit it to the study staff via REDcap. All participants will receive standard recommendations for physical activity, screen, and sleep time as per the American Academy of Pediatrics age appropriate recommendations at the first visit140. The study staff will perform weekly phone encounters with the participants to assess barriers to adherence and review the CGM data. If a barrier is identified the study staff will create a solution plan to promote adherence and retention. The study staff will record any medication changes or health issues that have occurred in the last 7 days. To foster treatment adherence, participants will receive weekly calls from the study staff for the duration of the trial. Counseling will be conducted by trained research staff. The sessions will serve three purposes: (1) foster adherence, retention, and accountability; (2) troubleshoot intervention barriers; and (3) monitor safety endpoints. During the sessions, participants will be provided with the support, knowledge, skills, and resources they need to successfully adhere to the protocol. The research staff will analyze the adherence data and progress using multiple-pass methodology. To support participants, the staff will use behavioral techniques, such as stimulus control, goal setting, behavioral contracting, and motivational interviewing. In addition, the staff will assist participants in troubleshooting any adherence issues and give participants additional encouragement and support when adherence problems arise. If a participant adheres to meal timing protocol < 4 days/week, a follow-up call or videoconference will be scheduled to address challenges and to counsel participants. Furthermore, In order to reduce participant burden, if at all possible study procedures will be scheduled to coincide with participants' scheduled clinical visits. (7) To further inform future trials and scalability we will continuously collect recruitment, consent, and retention rates, and barriers to engagement. (8) Adverse Event Monitoring will be monitored. If at any time, the study staff notices any unhealthy compensatory behaviors the PI will be notified and a treatment plan will be created to ensure that the participant receive the appropriate screening, work-up, and diagnosis from their primary care provider and are withdrawn from the study if appropriate. (9) The PI and research team will meet bi-weekly to monitor all study procedures and oversee data management and analysis.

Official Title
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Impact of Meal Timing on Glycemic Profiles in Adolescents With Type 2 Diabetes

Conditions
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Pediatric Obesity, Type 2 Diabetes, Time Restricted Eating

Intervention / Treatment
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* Behavioral: Time Limited Eating
* Behavioral: Components Common to All Study Arms.
* Behavioral: Control
* Device: Continuous Glucose Monitor


Participation Criteria
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Eligibility Criteria
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All adolescents with T2D and referred to the endocrinology clinic at CHLA will be screened. Inclusion criteria are: (1) age 12-21 years; (2) Tanner stage III and above; (3) diagnosis of T2D based on the ADA diagnostic guidelines; (4) hemoglobin A1c < 9%; and (5) participant must be willing and able to adhere to the assessments, visit schedules, and eating/fasting periods. To limit confounding factors, individuals will be considered ineligible to participate if they meet any of the following exclusion criteria: (1) previous diagnosis of Prader-Willi Syndrome, brain tumor or hypothalamic obesity; (2) serious developmental or intellectual disability; (3) previous diagnosis or subthreshold symptoms of an eating disorder (anorexia nervosa, bulimia nervosa, binge-eating disorder); (4) parent/guardian-reported physical, mental of other inability to participate in the assessments (e.g., inability to wear CGM, inability to undergo imaging testing without sedation); (5) previous or planned bariatric surgery; (6) current planned use of an anti-obesity or other diabetes medication (e.g., phentermine, topiramate, orlistat, glucagon-like-peptide-1 agonist, naltrexone, or bupropion); or (7) current participation in other interventional weight loss studies.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control: 12 hour eating period<br>Control: Habitual daily eating period (no meal time restrictions) | Behavioral: Components Common to All Study Arms.<br>* All participants will receive two hours of standard nutrition counseling recommended for adolescents living with T2D. No specific caloric restriction will be recommended. All participants will maintain their usual lifestyle, including physical activity and sleep patterns. Physical activity and sleep recommendations consistent with the American Academy of Pediatrics guidelines for adolescents will be encouraged but not formally prescribed.<br>Behavioral: Control<br>* Participants assigned to the control arm will be instructed to consume food over a 12-h or more eating window. No energy restriction will be required.<br>Device: Continuous Glucose Monitor<br>* All participants will be trained to wear a blinded continuous glucose monitor sensor using manufacturer educational materials under the supervision of research staff. Participants will be asked to wear the CGM for the duration of the study. During each study visit, the CGM reader will be connected to the site database to create an individual participant report. Participants will be provided enough sensors to replace the sensor every 14 days. The participants and guardians will be educated on how to use the CGM and receive 1:1 coaching on how to change the sensor, which will be completed either independently or under study team guidance. At each weekly phone meeting, study staff will monitor any challenges related to CGM wear, including participant discomfort, skin adherence, and other issues.<br>|
| Experimental: Time Limited Eating<br>Time Limited Eating: 8-hour eating period (16 hours of daily fasting). | Behavioral: Time Limited Eating<br>* The TLE intervention arm will involve instructing participants to consume their usual kind and amount of food and beverages (all calories) within a pre-specified 8-hour period, fasting for the remaining 16-hours. They will be free to divide their food and beverage intake into as many meals or snacks as desired during the 8-hour period. Participants will be allowed to consume non-caloric beverages (water, tea, coffee) during the fasting period. No energy restriction will be required.<br>* Other names: TLE;Behavioral: Components Common to All Study Arms.<br>* All participants will receive two hours of standard nutrition counseling recommended for adolescents living with T2D. No specific caloric restriction will be recommended. All participants will maintain their usual lifestyle, including physical activity and sleep patterns. Physical activity and sleep recommendations consistent with the American Academy of Pediatrics guidelines for adolescents will be encouraged but not formally prescribed.<br>Device: Continuous Glucose Monitor<br>* All participants will be trained to wear a blinded continuous glucose monitor sensor using manufacturer educational materials under the supervision of research staff. Participants will be asked to wear the CGM for the duration of the study. During each study visit, the CGM reader will be connected to the site database to create an individual participant report. Participants will be provided enough sensors to replace the sensor every 14 days. The participants and guardians will be educated on how to use the CGM and receive 1:1 coaching on how to change the sensor, which will be completed either independently or under study team guidance. At each weekly phone meeting, study staff will monitor any challenges related to CGM wear, including participant discomfort, skin adherence, and other issues.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in percent time in range | Change in percent time in range, as measured on CGM over the study period | Measured at week 0,4, 12 | 
| Change in Hemoglobin A1c | Change in hemoglobin A1c at week 12 compared to baseline | Week 12 compared to baseline | 
| Change in insulinogenic index | Change in insulinogenic index after mixed meal tolerance test | Week 12 compared to baseline | 
| Change in total body fat mass (kg) | Change in total body fat mass as measured by DEXA at week 12 compared to baseline | Week 12 compared to baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ASA 24 Dietary Recall | Twenty-four-hour dietary recalls will be conducted for all participants pre- and post-intervention. One weekday and one weekend day will be collected for all participants. | Measured at week 0,4, 12 | 
| International Physical Activity Questionnaire (IPAQ) | The International Physical Activity Questionnaire (IPAQ) has been developed to estimate levels of habitual physical activity across different countries and socio-cultural environments and will be collected at 5 time points. | Measured at week 0,4, 12 | 
| Munich Chronotype Questionnaire for children and adolescents (MTCQ) | The Munich ChronoType Questionnaire (MCTQ) is a self-rated scale to assess sleep structure, patterns, duration, and quality and will be collected at 5 time points. | Measured at week 0,4, 12 | 
| Pittsburg Sleep Quality Index | PSI self-reported sleep scale of quality and quantity | Measured at week 0,4, 12 | 
| Change in BMI in excess of the 95th percentile (%BMIp95) | Change in %BMIp95 | Measured at week 0,4, 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Time Restricted Feeding, Time Limited Eating, Pediatric Obesity, Type 2 Diabetes, Continuous Glucose Monitor