Impact of Meal Timing on Glycemic Profiles in Adolescents With Type 2 Diabetes
Study Details
Study Description
Brief Summary
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 (aged 14-21 years, all gender expressions, anticipate 60-70% Latinx), diagnosed within the last 6 months, with a hemoglobin A1c < 9%, and on Metformin monotherapy, 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
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 (ages 14-21 years) with T2D, diagnosed within the last 6 months, with hemoglobin A1c (HbA1c) < 9%, on Metformin monotherapy, 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:
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The staff will introduce the study to all eligible participants either in person or virtually and consent interested families for the study.
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All participants and their families will complete baseline study surveys in REDcap.
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All participants and their families will receive training on the use and application of the Dexcom G6 CGM139, 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.
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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.
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The study staff will conduct study assessments with participants at week -1, 0, 1, 4, 8, and 12.
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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.
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To further inform future trials and scalability we will continuously collect recruitment, consent, and retention rates, and barriers to engagement.
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Adverse Event Monitoring (See Human Subject Protection Plan for full details) 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.
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The PI and research team will meet bi-weekly to monitor all study procedures and oversee data management and analysis.
Baseline Screening:
Diabetes Knowledge: We will screen all participants for baseline diabetes knowledge after completing their new onset education process according to standard of care recommendations from the ADA. Per clinical standards and protocols at CHLA, each participant and family member will be required to complete new onset education and achieve 75% competency on administering Metformin daily at full dose, checking blood glucose as recommended (prior to starting the CGM as part of the study protocol), and recommended lifestyle modifications.
Eating Behaviors: Drs. Vidmar and Salvy will screen all participants for disordered eating at baseline to determine eligibility for participation. Any adolescent that has a previous diagnosis of disordered eating (anorexia nervosis, binge eating disorder or bulimia) will not be eligible to participate in the study. Any adolescent that exhibits disordered eating behaviors will be referred to their primary care provider for evaluation of disordered eating and not be eligible to participate in the study.
Feasibility of recruiting economically, racially, and ethnically diverse participants. CHLA's high-volume endocrinology clinic has had 96 patients with new onset T2D > 14 to < 21 years in the past year. Of those, 50 patients had a HbA1c < 9.0% and would have been eligible for the study. Based on our recruitment history in youth with T2D, we anticipate a consent rate of 40%, retention rate of 75%, and recruitment of 30 youth per year to reach our target recruitment of 90 adolescents by year 3. The demographics of our patient population are: mean age 16.9 years, 60% female, mean age of diagnosis 13.2 ± 2.3 years. Sixty-five percent of our patients self-identify as Latinx, compared to 47.5% of the population in Los Angeles.1 Approximately 80% of our patients report a family history of T2D. The mean %BMIp95 at diagnosis was 115% ± 21% and 123% ± 22% for females and males, respectively.
Retention Strategies:
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 either in-person or remotely via a HIPAA-compliant online meeting application. 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 review the adherence data and progress for the month 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, support, and create a specific plan 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. Drs. Vidmar and Salvy will provide the initial training as well as quarterly refresher training to the research staff providing counseling. Drs. Vidmar and Salvy will also provide regular supervision to address challenges and prevent drift. We will telephone participants one week prior and the day before scheduled visits to remind them of the study visit and help address any barriers (e.g., transportation).
Intervention fidelity encompasses integrity (interventions are implemented according to established procedures) and differentiation (interventions are distinct from one another). Our formative work suggest that the following strategies and safeguards are effective in preserving integrity and differentiation: (1) Comprehensive assessment of the standard of care avoids content overlap between intervention arms, (2) asking participants to record the time they started and finished eating every day, (3) frequent contacts with participants to review adherence to meal timing and to problem-solve issues and challenges encountered.
Adverse Event Monitoring: See Human Subjects Protection Plan
Intervention Components Participant and Study Team Interactions
The study team members will be required to have a bachelor's degree and at least one-year experience in clinical trial coordination and complete a structured training program. The study team members will come from a variety of backgrounds and professional experiences. The study team members are not required to have achieved or maintained significant weight loss themselves as previous research on coaching interventions suggests that characteristics such as communication skills and empathy are more crucial to success in this role. To assess intervention fidelity, each month the PI and Dr. Salvy will observe phone conversations and in-person study visits on 5 participants from each intervention group. The study team and adolescent will interact via monthly face-to-face visits (approximately 2 hours each) and 12 weekly phone calls (15 minutes each). Participants will complete validated surveys at each visit via REDcap and the study team will use a qualitative semi-structured interview utilizing motivational interviewing (MI) techniques to elicit both positive and negative impacts on weight management, the TLE approach, and CGM use, and to identify any barriers to adherence and retention and monitor for any unhealthy compensatory eating behaviors.
Each study team member will have a cell phone used solely for the purpose of this study so that participants may directly contact the study team regarding any questions or concerns. Phone calls and text messages will be utilized for appointment reminders, scheduling weekly phone meetings, providing emotional support, and following up on items discussed in a prior visit or phone call. All interactions will be documented in a database created for the study, including date, time, type, and duration of contact, topics discussed, and any relevant notes. The study team delivering the curriculum will receive 10 hours of training over a 4-week period from the PI, Dr. Salvy, and a registered dietitian. The training will cover: 1) the importance, rationale and education about the TLE approach and CGM use, 2) the concept of behavior change, patient-centered approach and MI techniques, and 3) practical advice specific to each stage of the intervention and ways to assist the adolescent with common barriers and triggers. The curriculum will cover active listening, non-judgmental communications, MI techniques, and creating self-management goals. In addition, the study team will be required to demonstrate understanding of the curriculum, TLE approach, and CGM use through simulated role-plays and observations of participant sessions.
Components Common to All Study Arms. 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.
Time Limited Eating. 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. We conducted a cross sectional analysis of a cohort of 100 adolescents with obesity and found that most total calories, carbohydrates, and added sugars were consumed between 11 AM and 7 PM. In addition, in our feasibility trials, most adolescents selected an afternoon/evening eating window consistent with their shifting sleep/wake cycle and timing of social engagements. Therefore, to align with the normal developmental eating patterns seen in adolescents, we will implement an afternoon/evening TLE approach (consumption of all calories between 12:00 and 20:00 seven days per week). Participants will be allowed to consume non-caloric beverages (water, tea, coffee) during the fasting period. No energy restriction will be required.
Control. 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.
Adherence Monitoring: All participants will be asked to record the time they start and finish eating each day and to report their eating windows to the study staff weekly. Each week, the study staff will report the reported time of all food and beverage intake to monitor participant adherence to the designated eating window. To determine the daily eating window, the time interval between the first and last caloric intake of the day will be calculated. These self-reported time windows will be verified by examining the pattern of glucose excursions using the 24-h CGM data.
Continuous Glucose Monitor. All participants will wear a Dexcom G6 continuous glucose monitors (Dexcom, San Diego, CA, USA) continuously for 13 weeks (week -1 to week 12 of the study period). All participants will be blinded to CGM data for seven days for baseline data collection (1 week), and then randomized. Participants will be provided with a transmitter and enough sensors to replace the sensor every 10 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. No glucometer calibration will be required. At each weekly phone meeting, study staff will monitor any adverse events and challenges related to CGM wear, including participant discomfort, skin adherence, and other issues.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Control: 12 hour eating period Control: Habitual daily eating period (no meal time restrictions) |
Behavioral: Components Common to All Study Arms.
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.
Behavioral: Control
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.
Device: Continuous Glucose Monitor
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.
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| Experimental: Time Limited Eating Time Limited Eating: 8-hour eating period (16 hours of daily fasting). |
Behavioral: Time Limited Eating
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. We conducted a cross sectional analysis of a cohort of 100 adolescents with obesity and found that most total calories, carbohydrates, and added sugars were consumed between 11 AM and 7 PM. Participants will be allowed to consume non-caloric beverages (water, tea, coffee) during the fasting period. No energy restriction will be required.
Other Names:
Behavioral: Components Common to All Study Arms.
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.
Device: Continuous Glucose Monitor
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.
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Outcome Measures
Primary Outcome Measures
- Change in percent time in range [Measured at week 0,4, 12]
Change in percent time in range, as measured on CGM over the study period
- Change in Hemoglobin A1c [Week 12 compared to baseline]
Change in hemoglobin A1c at week 12 compared to baseline
- Change in insulinogenic index [Week 12 compared to baseline]
Change in insulinogenic index after mixed meal tolerance test
- Change in total body fat mass (kg) [Week 12 compared to baseline]
Change in total body fat mass as measured by DEXA at week 12 compared to baseline
- Change in liver fat fraction [Week 12 compared to baseline]
Change in liver fat fraction as measured by MRI-PDFF at week 12 compared to baseline
Secondary Outcome Measures
- Nutrient Data System Recall (NDSR) 24 Hour Dietary Recall [Measured at week 0,4, 12]
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.
- International Physical Activity Questionnaire (IPAQ) [Measured at week 0,4, 12]
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.
- Munich Chronotype Questionnaire for children and adolescents (MTCQ) [Measured at week 0,4, 12]
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.
- Pittsburg Sleep Quality Index [Measured at week 0,4, 12]
PSI self-reported sleep scale of quality and quantity
Other Outcome Measures
- Binge eating disorder screen [Measured at week 0,4, 12]
The 7 item Binge-Eating Disorder Screener is a brief screener for BED, can assist physicians in identifying patients who may have BED and making the necessary follow-up decisions related to patient referrals or additional assessment and potential diagnosis of BED.
- Dutch eating behavior Questionnaire [Measured at week 0,4, 12]
The DEBQ will be used to assess participants' approach to food and eating along three dimensions: emotional, external, and restrained eating. There is a high degree of stability for each of these three eating behavior scales. The DEBQ has high internal consistency and validity. We will compare changes in DEBQ scores across study arms to monitor possible iatrogenic effects of TLE.
Eligibility Criteria
Criteria
All adolescents with T2D and referred to the endocrinology clinic at CHLA will be screened. Inclusion criteria are: (1) age 14-21 years; (2) Tanner stage III and above; (3) diagnosis of T2D based on the ADA diagnostic guidelines; (4) hemoglobin A1c < 9% on Metformin monotherapy (based on the ADA and International Society for Adolescent and Pediatric Diabetes recommendations. At CHLA we currently recommend Metformin Monotherapy for any patients with HbA1c <9% at onset and therefore will use this cut off for the study); 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, buproprion, SGLT-2 Inhibitor, insulin etc.); or (7) current participation in other interventional weight loss studies.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital of Los Angeles | Los Angeles | California | United States | 90027 |
Sponsors and Collaborators
- Children's Hospital Los Angeles
Investigators
- Principal Investigator: Alaina Vidmar, MD, Children's Hospital Los Angeles
Study Documents (Full-Text)
More Information
Publications
None provided.- CHLA-102020