Time Limited Eating in Adolescents With Type 2 Diabetes (KT2D)
Phase: NA
Conditions: Pediatric Obesity, Type 2 Diabetes, Time Restricted Eating
Sponsor: Children's Hospital Los Angeles

Title: Impact of Meal Timing on Glycemic Profiles in Adolescents with Type 2 Diabetes 
NCT Number: NCT04536480 
Date of Document: 2/28/2022 
Version: 7 
PI: Alaina Vidmar, MD 
Center for Diabetes, Endocrinology, and Metabolism 
Children’s Hospital Los Angeles 
Los Angeles, CA 90027 
 
 

1. SIGNIFICANCE  
 
1.1. Increased pediatric obesity has been accompanied by a rising incidence of T2D in adolescents, 
specifically among Latino and Black youth.72–74 Because the risk of complications in adults increases with 
both the duration of diabetes and the lack of glycemic control, it is imperative to achieve and sustain metabolic 
control in adolescents.22,23 The Restoring Insulin Secretion Consortium showed that compared to adults, 
adolescents with T2D have higher levels of insulin resistance and rapid, progressive β-cell failure despite early 
treatment with pharmacotherapies.22,75,76 Diet alone can improve glycemic control in adults with T2D, but little is 
known about the impact of dietary interventions in the early stages of T2D in adolescents. 95–103 The American 
Diabetes Association recommends that high-intensity dietary interventions be utilized to achieve a 500–
750 kcal/day energy deficit and maintain >5% weight loss in adults living with T2D.104,105 In adolescents with T2D, 
standard treatment is centered on pharmacotherapies, including insulin and Metformin, with the goal of improving 
glycemic control and preventing glycemic excursions, however minimal weight loss is achieved with these 
methods.105,106 There is a paucity of research evaluating the effectiveness of dietary interventions to reduce body 
fat mass, improve β-cell responsiveness, and prevent insulin dependence in this age group.79,85,89,107,108 
Conventional pediatric obesity treatment comprehensively addresses nutritional, physical activity, and behavioral 
topics with the goal of achieving clinically meaningful weight loss. Adherence to comprehensive lifestyle 
interventions is challenging for adolescents, in part because these approaches require frequent monitoring and 
engaging in multiple behavioral targets continuously. Therefore, there is a growing interest in simplifying 
intervention recommendations to decrease reliance on numeracy (Kilo calories and macronutrients), goal-setting 
and complex skillsets. One simpler approach is based on timing of eating.6–8,13,15,26–37  
 
1.2. Time-based interventions, such as time-limited eating (TLE), have become a promising dietary 
strategy for weight loss, glucose and lipid metabolism improvements, and overall well-being in 
adults.1,6,8–10,113–132 It has been shown in rodent and human studies that misalignment between endogenous 
circadian clock rhythms and rhythms of meal timing and sleep/wake induces weight gain and metabolic 
disruptions.9,109–112 TLE is a dietary approach that involves shortening the eating window to a pre-specified 
number of hours per day and fasting for the remaining hours of the day without necessarily altering diet quality 
and quantity.113 TLE has also been shown to improve fasting glucose and postprandial glucose levels, mean 
daily glucose, and insulin resistance, as well as blood triglyceride, and total cholesterol in adults with obesity and 
T2D. 10,114–116 The results of TLE in adults appear to depend on when eating occur.10,52,117 Previous evidence has 
shown glucose tolerance, skeletal muscle fatty acid oxidation, and diet-induced thermogenesis are higher in the 
morning than in the evening in adults with T2D.  Consumption of an evening meal induces higher postprandial 
glucose concentrations and insulin resistance compared with the same meal consumed in the morning. 118–121 
Many adult trials have thus promoted TLE early in the day because it has been hypothesized to synchronize the 
central and peripheral circadian clocks involved in energy expenditure and fat oxidation and minimizes glycemic 
excursions and endogenous glucose production.10,52,117  
 
1.3. No trial to date has studied the effects of TLE on glycemic control and body composition in 
adolescents with T2D. Because of its simplicity, TLE may represent a more feasible approach for adolescents 
than other caloric restriction regimens because it does not require extensive nutritional knowledge and control 
of food quantity and quality.5,85,86 However, an early eating window may conflict with many adolescents’ shifting 
chronotype, or preference to stay awake later and sleep later.122–127 This shifting chronotype, coupled with 
increasing sex steroids and growth hormone levels overnight, has been shown to cause increased insulin 
resistance in the early morning for this age group, contrary to what is seen in adults.128–131 This age-related 
changing metabolic state may provide an argument for an afternoon/evening eating window for TLE 
implementation in this age group. Our preliminary data, collected in 50 adolescents with obesity without diabetes, 
and 15 adolescents with T2D, shows the feasibility, acceptability, and safety of implementing 8-hour TLE in this 
age group and confirms that when allowed to self-select their eating window, the majority chose an 
afternoon/evening period.14,15 Thus, to further investigate the effect of TLE on cardiometabolic outcomes in 
adolescents with T2D, we aim to determine if late TLE minimizes glycemic excursions, delays β-cell deterioration, 
and reduces body fat mass compared to a prolonged eating period.   
 
2. INNOVATION: The proposed study is theoretically and clinically innovative for the following reasons:  
2.1. This study is the first trial evaluating the effect of TLE in adolescents with T2D on glycemic variability 
and β-cell function in a real-life setting. TLE is an easy-to-use dietary approach for adolescents with T2D that 

does not require additional resources. This study will collect preliminary efficacy data on how TLE effects glucose 
control, β-cell function, and body composition.  In addition, in this study participants will be prescribed an 
afternoon/evening eating window to align with social preference and eating habits. Thus, this data will add to the 
growing literature exploring how the efficacy of TLE is impacted by the timing of the eating window.  
 
2.2. Shift in standard of care.  There is a lack of time-based recommendations in current nutrition standards 
for adolescents with T2D. Results from this study could potentially change the way adolescents with T2D are 
treated in the future by incorporating meal-timing behaviors as part of their medical regimen. 
 
2.3. New insights on progression to β-cell dysfunction. β-cell dysfunction at time of diagnosis may be 
reversible; yet there is a paucity of research evaluating if TLE can delay β-cell loss of function and disease 
progression in adolescents with T2D. By utilizing C-peptide, insulin, and glucose measures over time after the 
MMTT, coupled with data collected from CGM, this study has the potential to show how time-based dietary 
interventions effect insulin secretion and function in adolescents with T2D and delay β-cell deterioration. 
 
3. APPROACH 
3.1. Preliminary, Feasiblity, and Process Measure Data:  
3.1.1. 8-hour TLE + CGM is feasible, acceptable, and safe in adolescents with obesity.14,15   
We conducted a 12-week pilot study to examine the 
feasibility of 8-hour TLE combined with continuous glucose 
monitoring in adolescents with obesity, without diabetes 
compared to a prolonged eating window. Fifty adolescents with 
BMI ≥95th percentile received standard nutritional counseling, 
wore a CGM daily, and were randomized to: (1) Prolonged 
eating window: 12 h eating/12 h fasting + blinded CGM; (2) TLE 
(8 h eating/16 h fasting, 5 days per week) + blinded CGM; (3) 
TLE + real-time CGM feedback. Forty-five participants 
completed the study (16.4 ± 1.3 years, 64% female, 49% 
Hispanic, 75% public insurance, 70% annual household 
income <$50,000). Ninety percent of adolescents in the TLE 
groups selected to start their eating window between 10 AM 
and 12 PM (11AM-8PM, 81%). To monitor the dosage of the 
intervention received, all participants recorded their eating 
windows daily and reviewed those logs with study staff weekly. 
Self-reported eating periods were compared weekly to the 
CGM data to monitor for large glycemic excursions during a 
reported fasting period which might suggest a meal was 
consumed. These excursion periods were then reviewed with 
the participant by the study team to reinforce adherence. 
Overall, there was high adherence to the prescribed eating 
windows (TLE 5.2 d/wk [SD 1.1]; control 6.1 d/wk [SD 1.4]) and 
daily CGM wear (5.9 d/wk [SD 4.8]) across all participants with 
no difference noted between groups. Most of the adolescents 
(90%) assigned to TLE reported that limiting their eating 
window was feasible without negative impact on daily 
functioning or adverse events. Based on adolescents’ responses to the Satisfaction Survey and exit interviews, 
TLE was viewed favorably. Post-intervention, 26% of the TLE + blinded CGM group lost >5% of their baseline 
weight vs. 31% in the TLE + real time CGM and 13% in the control group (no between group difference in mean 
percent weight loss p = 0.5, Figure 1). Consistent with intention-to-treat analysis, across the study period, there 
was a significant decrease in excess percent of the 95th percentile (%BMIp95) across all three groups (Control 
(n=15): −3.27±3.34, TLE + blinded CGM (n=19): −3.76±5.76, and TLE + real time CGM (n=16): −4.85±5.08, with 
no significant difference between groups (p=0.7; Figure 2).  Across all secondary outcomes there were no 
between group difference in terms of energy intake, quality of life, physical activity, or eating behaviors. Thus, 
data from this study indicate that we can reliably recruit and retain adolescents with obesity, without diabetes, to 
participate in a TLE intervention and that decreasing their eating window is acceptable to them. In addition, our 
findings indicate that we can consistently monitor the dosage of the intervention received through a combination 
-10
-8
-6
-4
-2
0
%BMI      change from week 0 (median)
0
4
8
12
Week
12+bCGM
8+bCGM
8+rtCGM
p95
Figure 1. Percent weight loss at week 12 
across study participants. Black: Control, 
Red: TLE + blinded CGM, Blue: TLE + 
real time CGM. 
 
Figure 2. Change in 
%BMIp95 between groups. 
Black: Control, Red: TLE 
+ blinded CGM, Blue: TLE 
+ real time CGM. 

of daily logs, dietary intake, and evaluation of glycemic excursions on CGM. These preliminary data provide a 
strong premise for the study design of our proposed trial in adolescents with T2D.  
 
3.1.2. 8-hour TLE + CGM is feasible, acceptable, and safe in adolescents with T2D.   
We have been conducting a 12-week feasibility study (funded by the Pediatric Endocrine Society Clinical 
Scholar Award) to substantiate the feasibility, acceptability, and safety of TLE in adolescents with T2D. To date, 
fifteen adolescents with T2D (mean age 16.35 +1.26 years 70% female, 79% Latinx, 75% public insurance), 
diagnosed within the last 6 months, with a hemoglobin A1c < 9%, and on Metformin monotherapy have been 
recruited and randomized to one of two meal-timing schedules for 12 weeks: (1) Control: >12-hour eating period 
or (2) TLE. All participated record their eating window daily and submit it to the study staff via REDcap survey.  
Since open enrollment September 2021, 41 participants have been screened, 23 met eligibility criteria, and of 
those 15 were enrolled, which achieved a recruitment rate of 65% for those who were contacted about the study. 
No participants have withdrawn from the study to date. To monitor the dosage of the intervention received, 
participants recorded their eating windows daily and reviewed those logs with study staff weekly. Overall, there 
has been high adherence to the prescribed eating windows (TLE 6.4 d/wk [SD 1.1]; control 6.6 d/wk [SD 1.4]) 
and daily CGM wear (6.4 d/wk [SD 4.8]) across all participants with no difference noted between groups. All eight 
participants assigned to TLE reported that limiting their eating window and wearing a CGM was feasible without 
negative impact on daily functioning or adverse events. To monitor safety, weekly CGM data was reviewed for 
episodes of hypoglycemia (defined as glucose level <70 mg/dL). For all participants to date, there have been no 
episodes of hypoglycemia captured on CGM. Thus, data from this study indicate that we can reliably recruit and 
retain adolescents with T2D to participate in a TLE intervention, monitor treatment adherence closely, and that 
decreasing their eating window is acceptable to them. Our findings indicate that TLE is a feasible and safe 
intervention for adolescents with T2D. These preliminary data provide a strong premise for the feasibility of our 
proposed trial. 
 
3.2. Overview of Proposed Study Design:  
The aim of this study will be to compare cardiometabolic effects of TLE (8-h eating period/16-h of daily 
fasting) versus a prolonged eating period (12+h eating period) in a randomized pilot study with careful control of 
continuous adherence to prescribed eating window.  The implementation steps of the proposed study are as 
follows (See Table 3): (1) The staff will introduce the study to all eligible participants either in person or virtually 
and consent interested families for the study; (2) All participants and their families will complete baseline study 
surveys in REDcap; (3) All participants will be trained to wear a blinded CGM using manufacturer educational 
materials under the supervision of research staff. Participants will be asked to change the CGM sensor every 14 
days 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. All equipment required for the duration of the study will be distributed 
to the participants at consent. Participants will receive enough sensors to wear the CGM daily for the entire study 
period. (4) 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 or (2) TLE. 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 visit132;  (5) 
The study staff will conduct study assessments with participants at week 0, 4, and 12; (6) The study staff will 
perform weekly phone encounters with the participants to assess barriers to adherence including diabetes 
specific components (Metformin side-effects, adjustment to diagnosis, etc.) and eating practices (responding to 
hunger cues, managing fasting periods in social situations, etc.). 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. The PI will review CGM downloads collected at each study visit to 
ensure no diabetes treatment escalation is required. Per clinical protocol at CHLA for adolescents with T2D on 
Metformin monotherapy, adolescents will check blood glucose with a glucometer twice weekly and be instructed 
to notify the clinical diabetes team for any blood glucose levels out of target range; (7) To further inform future 
trials and scalability we will continuously collect recruitment, consent, and retention rates, and barriers to 
engagement; (8) Adverse events (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. (9) The PI and research team will meet 
bi-weekly to monitor all study procedures and oversee data management and analysis. 
 
3.3. Participants: We will recruit 100 adolescents (age 14-21 years at enrollment, all gender expressions), with 
T2D. Inclusion criteria are: (1) age 14-21 years; 
(2) Tanner stage III and above; (3) diagnosis of 
T2D based on the ADA diagnostic guidelines104; 
(4) hemoglobin A1c < 9% on Metformin 
monotherapy (At CHLA, based on the ADA and 
International 
Society 
for 
Adolescent 
and 
Pediatric Diabetes recommendations104,105,133,  
we 
currently 
recommend 
Metformin 
monotherapy for any patients with HbA1c <9% at 
onset and therefore will use this cut off for the 
study); (5) participant must be willing and able to 
adhere to the assessments, visit schedules, and 
eating/fasting periods; and (6) baseline eating 
window greater than 10 hours. To limit 
confounding 
factors, 
individuals 
will 
be 
considered ineligible to participate if they meet 
any of the following exclusion criteria: (1) 
diagnosis of Prader-Willi Syndrome, brain tumor 
or hypothalamic obesity; (2) serious 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; 
(5) previous bariatric surgery; (6) current use of 
an anti-obesity or other diabetes medication (e.g., phentermine, topiramate, orlistat, glucagon-like-peptide-1 
agonist, naltrexone, buproprion, SGLT-2 Inhibitor, or insulin); or (7) current participation in other interventional 
weight loss studies. A random block stratified randomization scheme will be used. Participants will be 
randomized 1:1 via stratified, blocked randomization to ensure the groups are balanced in terms of number of 
participants and distribution of potential confounding variables including sex and age.  
 
3.4. Feasibility of recruiting economically, racially, and ethnically diverse participants. The CHLA 
endocrinology clinic has seen 160 patients with new onset T2D (> 14 to < 21 years old) in the past year. Of 
those, 60 patients had an HbA1c < 9.0% and would have been eligible for the study. We will also recruit from 
affiliate hospitals and pediatric clinics in the area. 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 Latino, compared to 47.5% of the population in Los Angeles.134 At CHLA, we have a long history of conducting 
investigator-initiated studies in youth with T2D, including large consortium studies such as the Treatment of 
Diabetes in Adolescents and Youth (TODAY) trial25, SEARCH for diabetes in youth18,71 and Prevent Diabetes 
Consortium (PDC).135 At CHLA, the recruitment rate in this population is between 50-60% with a retention rate 
of 60-80%. Based on the recruitment history from our feasibility trials, we anticipate a consent rate of 50-60%, 
retention rate of 75-80%, and recruitment of 35 adolescents per year to reach our target recruitment of 100 
adolescents by year 3.  
 
3.5. 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. The sessions will serve 
three purposes: (1) foster adherence, retention, and accountability; (2) troubleshoot intervention barriers; and 
(3) monitor safety endpoints. To support participants, the staff will use behavioral techniques, such as stimulus 
control, goal setting, behavioral contracting, and motivational interviewing. In order to reduce participant burden, 
if at all possible study procedures will be scheduled to coincide with participants’ scheduled clinical visits. 
 
3.6. Intervention Arms:  
Table 3: Study Procedures and Measures 
 
 
 
Weeks  
0 
4 
 12 
Consent Completed 
x 
 
 
Medical history 
x 
 
 
Demographic Data 
x 
 
 
CGM Education and equipment  
x 
 
 
CGM (sensor change every 14 d, 12 w wear time) 
x 
x 
x 
Randomized 
x 
 
 
Primary Outcomes 
 
 
 
Glycemic Control 
 
 
 
Percent Time in Range 
x 
x 
x 
Hemoglobin A1c 
x 
 
x 
Mixed Meal Tolerance Test  
 
 
 
Insulinogenic Index  
x 
 
x 
Body Composition  
 
 
 
DEXA Scan: Total body fat (Kg) 
x 
 
x 
MRI-PDFF: Total liver fat fraction 
x 
 
x 
Secondary Outcomes 
 
 
 
Nutrient Data System Recall: 24-hour dietary recall 
x 
 
x 
International Physical Activity Questionnaire 
x 
x 
x 
Pittsburg Sleep Quality Index and Chronotype Questionnaire 
x 
x 
x 
Monitoring for Adverse Events 
 
 
 
Dutch Eating Behavior Questionnaire 
x 
x 
x 
Binge Eating Disorder Screen 
x 
x 
x 

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 8 
PM.136 In addition, in our feasibility trials, most adolescents selected an afternoon/evening eating window for 
both week days and weekend days, consistent with their shifting sleep/wake cycle and timing of social 
engagements.14 Therefore, to align with the normal developmental eating patterns seen in adolescents, we will 
assign an afternoon/evening TLE approach (consumption of all calories between 12:00 and 20:00 [plus or minus 
1 hour] 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-hour or more 
eating window. They will be free to divide their food and beverage intake into as many meals or snacks as desired 
during the 12-hour period. No energy restriction will be required.  
 
Adherence Monitoring and Intervention Fidelity: To ensure differentiation between the intervention arms all 
participants will be asked to record the time they start, and finish eating each day and provide their eating logs 
to the study staff weekly. Each week, study staff will determine the daily eating window for each participant by 
reviewing the time interval between the first and last caloric intake of the day. These self-reported time windows 
will be verified by examining the pattern of glucose excursions using the 24-h CGM data. If a participant adheres 
to meal timing protocol < 4 days/week, a follow-up call or videoconference will be scheduled to address 
challenges, give participants additional encouragement, support, and create a specific plan to promote 
adherence.  
 
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. 
 
3.7. Measurements: The study team will conduct all assessments at week 0, 4, and 12. All data will be collected 
and stored in REDCap. 
 
Aim 1: Test the effect of TLE on glucose control and β-cell function in youth with T2D.  
Quantifying glycemic control (%TIR): Using a CGM, we will capture glucose readings every 5 minutes and 
obtain the weekly %TIR (defined as glucose levels from 70 mg/dL to 180 mg/dL104) over the course of the study. 
Vigersky et al. demonstrated that a 10% change in the %TIR is equivalent to a 0.8% change in HbA1c.137 
Hemoglobin A1c: HbA1c will be measured from whole blood collected at the CHLA laboratory at week 0 and 
12. HbA1c will be measured using a DCA 2000 (Bayer Corporation, Elkhart, IN). 
Quantifying change in β-cell function: Change in Insulinogenic index (IGI) after MMTT: The MMTT provides 
a simultaneous estimate of insulin secretion and sensitivity.137–142 To improve participant burden and decrease 
project cost, the modified MMTT will be utilized.  Previous adult TLE trials have utilized the IGI as a surrogate 
marker of β-cell function in TLE trials.10 Therefore, we will evaluate the effect of TLE on changes in IGI measured 
after MMTT. The MMTT will be performed at weeks 0 and 12. Participants will be instructed to not take their 
Metformin for 48 hours prior to their MMTT. Following baseline sampling (0 min), one 8-fluid-ounce Boost 
nutrition supplement drink (Nestlé Health Science) will be consumed. C-peptide, glucose, and insulin 

concentrations will be measured in duplicate from plasma samples using YSI 2900 analyzer (YSI Life Sciences, 
Yellow Springs, OH, USA). Insulin and C-peptide concentrations will be measured using plasma with a 
commercially available ELIZA (Alpco Ltd, Windham, NH, USA), in duplicate. Total area under the cure (AUC) 
will be calculated for venous glucose, insulin, and c-peptide concentrations using the trapezoid methods using 
GraphPad Prism (Version .01, GraphPad Software Inc, San Diego, CA, USA).  
 
Statistical Consideration (For Full Plan See Statistical Analysis Section): The sample size estimates, and 
analytical plans were developed under the guidance of Dr. Ramon Durazo-Arvizu. Descriptive statistics, including 
graphical depictions, will be utilized to assess the degree of symmetry/normality of continuous outcomes and 
identification of outliers. The statistical approach will be implemented with and without transformations in addition 
to generalized linear mixed models, when appropriate.  All regression models will be adjusted for baseline levels, 
as this adjustment increases power.143,144 A false discovery rate (FDR=10%)145 approach will be applied to 
assess the effect of multiple testing. Statistical analyses will be performed using STATA 17.0 (STATA Corp, 
College Station, TX). Statistical analyses will be crafted under three different mechanisms, namely missing 
completely at random, missing at random, and other missing data patterns to account for missing data.146–149 
Our first approach to statistical analysis with missing data will follow common practice, such as last value carried 
forward, and multiple imputations.150–153 Last value carried forward and multiple imputation will be carried out to 
generate complete data prior to analyzing data under the intention-to-treat (ITT) principle. A per-protocol analysis 
will also be performed and compared to results obtained under ITT. 154 Intervention adherence for all participants 
will be continuously monitoring and accounted for in the analysis process. To account for partial compliance, we 
will also complete an as treated approach to compare intervention arms by the actual intervention dosage they 
received. For participants with partial compliance, the treatment effect will be estimated by regressing the degree 
of compliance on the outcome in a logistic regression model. Participants will be compliers if they have complied 
with at least 80% of the intervention according to protocol.155–159 No studies in the literature specifically addressed 
all our aims. Nevertheless, we were able to extract reasonable effect size information from several intervention-
based studies, including some TLE studies conducted in adults.10,47,49,50,160 The primary outcomes for Aim 1 are 
the difference between TLE and control in: a) average %TIR overtime, b) HbA1c at week 12 compared to 
baseline, and c) average IGI after MMTT at week 12 compared to baseline.  
 
a) Percent Time in Range (%TIR): A two-step analysis plan will be executed starting with: 1) A change variable 
(%TIR at week 12 minus %TIR at week 0) will be generated for each study participant and average values 
adjusted for baseline %TIR and confounders compared via multivariable linear regression; 2) The previous 
analysis techniques do not take full advantage of the repeated measures in each individual.  A multivariable 
linear mixed effect model with random intercept (LME) will be fit to compare the two treatment arms. Extracting 
from adult data, and data from youth with type 1 diabetes, a change in %TIR of greater than 5% is considered 
clinically significant, this correlates with an estimated change in HbA1c of -0.4%. Because we targeted 
improvements in %TIR, a one-sided at a 5% significance level to detect a benefit of TLE compared to control 
was used for each comparison, with a conservative within-subject correlation of 0.6. The required sample size 
to detect a pre-specified effect size (Cohen’s d) of 0.34 with 80% power using an LME models (adjusting for 
baseline %TIR) with three %TIR determinations at weeks 0, 4, and 12 results in 40 subjects per group (80 
total).161 A 20% attrition rate was observed in our preliminary data thus the attrition-adjusted total sample size is 
100 (80/0.8) participants. Furthermore, data extracted from adult studies suggests that the standard deviation of 
%TIR is between 16 and 25%.137 Thus, a 0.34 effect size and a standard deviation of about 20% (midpoint 
between 16 and 25) amounts to a difference in %TIR of about 6.8% (0.34*20% = 6.8%).  
b) Change in HbA1c: As above a two-step approach will be implemented. First, a two-sample, one sided, 5%-
significance t-test to test the mean difference in HbA1c from baseline to week 12 between TLE and control. 
Second, a multivariable regression model will be fit. Calculations are based on the latter model. Carter et al. 
examined the impact of intermittent energy restriction compared to continuous energy restriction in adults with 
T2D and found that there was a between group difference of -0.2% with an SD of 0.1%.14 On the other hand, 
Toledo-Corral, et. al. estimates the mean and standard deviation of HbA1c among children aged 8-17 years of 
about 5.75% and 0.2%, respectively.162 An application of a one-sided, two-sample, 5%-significance t-test with 
50 participants per intervention group (40 prior to attrition adjustment) will detect an effect size (mean HbA1c 
change) of -0.12% with 85% power, assuming a correlation between week 0 and week 12 HbA1c determinations 
of about 0.6.   
c) Insulinogenic Index after MMTT:  To evaluate the difference in β-cell function between TLE and control we 
will measure the difference in IGI change following MMTT at week 12 compared to baseline utilizing a two-

sample, one-sided, 5%-significance t-test. A multivariable linear regression model will be fit to the data to 
compare mean IGI change adjusting potential confounders, including baseline IGI values. A recent pilot study of 
TLE in an adult cohort without diabetes, showed TLE increased the IGI by 14 ± 7 U/mg compared to control at 
week 6 compared to baseline.10 A total sample size of 100 participants (80 before adjusting for attrition) will thus 
detect a difference in IGI change of 4.2 with 85% power using the 5%-significance, one-sided, two-sample t-test. 
Additional power is gained by adjusting for baseline IGI and unbalanced participant characteristics. 
 
Aim 2: Test the effect of TLE on obesity and liver fat in recently diagnosed youth with T2D.  
Quantification of body composition: Total Body Fat: Using a Hologic QDR 5400 densitometer (Hologic, Inc., 
Bedford, MA) DEXA scan, we will measure the change in TBF at week 12 compared to baseline between TLE 
and control. Liver Fat Fraction: Change in liver fat will be measured by magnetic resonance imaging proton 
density fat fraction (MRI-PDFF). Participants will undergo MRI screening examinations at baseline and week 12 
using an advanced magnitude-based spoiled-gradient-echo MRI-PDFF estimation technique previously 
validated to measure hepatic steatosis in children.163–167 Key MRI-PDFF scanning parameters will be: 3T MRI 
scanner (GE 3T 750, and Siemens 3T TrioTim), 2D axial spoiled-gradient-echo breath hold acquisitions, TR > 
100 ms, six TE values evenly spaced from 1.15 to 6.9 ms, flip angle 10 degrees, number frequency-encoding 
steps between 140 and 192, number phase-encoding steps between 128 and 140, no filters, no saturation, slice 
thickness 6 to 10 mm (contiguous), and rectangular field-of-view to accommodate body habitus. 163 
 
Statistical Consideration: We will utilize multivariate linear regression model to adjust for potentially 
unbalanced variables across group, in particular baseline values. A recent systematic review of the impact of 
TLE on cardiometabolic outcomes, showed that in adults TLE has variable effect on total body fat mass with 
some studies showing a decrease of up to 4 kg compared to control and others showing no change in TBF and 
liver fat fraction compared to control.168–170 A previous study estimated the mean and standard deviation of Liver 
Fat Fraction among youth with obesity (ages 12-18 yrs.), is about 8%+ 8%, respectively. A between-group mean 
change difference in liver fat fraction as large as 3.25 will be detected with 81% power.  
 
Aim 3: Test the effect of TLE on sleep, physical activity, and dietary intake.   
Secondary Outcomes: Twenty-four-hour dietary recalls will be conducted for all participants pre- and post-
intervention via the Nutrient Data System Recall (NDSR) 24 Hour Dietary Recall171. One weekday and one 
weekend day will be collected for all participants. Physical activity will be measured with the International Physical 
Activity Questionnaire (IPAQ).172–177 The IPAQ has been developed to estimate physical activity across different 
countries and socio-cultural environments and will be collected at 5 time points. Adult trials of TLE have reported 
sleep improvement upon shortening daily eating windows and so to analyze sleep we will collect the Munich 
Chronotype Questionnaire for children and adolescents (MTCQ)178,179 and Pittsburg Sleep Quality Index (PSI)180–
182 at five time points. The MCTQ is a self-rated scale used to estimate an individual’s circadian preference by a 
single phase-reference point, the mid-sleep point on free days. The PSI evaluates seven components of sleep 
architecture, sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of 
sleeping medication, and daytime dysfunction.  
 
Statistical Consideration: All outcome variables (sleep, physical activity, and dietary intake) will be treated as 
continuous. The ladder of transformations approach150,151 will be implemented to improve symmetry and/or 
approximate normality of their distribution. The study was not powered to assess mediation or moderation of 
each secondary outcome; however, we will estimate direct and indirect effects of the interaction between the 
outcomes. Given the estimated sample size, and desired statistical power, the minimal effect size (Cohen’s d) is 
estimated, under the assumption of 0.6 correlation of each of the outcome variables between baseline (week 0) 
and follow-up (week 12). A 5%-significance, one-sided, two-sample t-test with the operating characteristics 
described above will detect an effect size as large as 0.5 (mean difference in standard deviation units). As an 
alternative to hypothesis testing, we will determine 95% confidence intervals in response to the interventions.183–
186 Confidence intervals not only allow for a better interpretation of effect estimates and their variability but could 
also be used to discriminate between group differences. Although results from this study will be evaluated using 
traditional techniques, such as p-values, we will rely on interpretation via confidence intervals. As a result, 
parameter estimates (e.g., mean difference, change and trends) will be used to aid scientific reasoning.183  
 
  
 
 

PROTECTION OF HUMAN SUBJECTS 
1) RISKS TO HUMAN SUBJECTS:  
a) Human Subject Involvement, Characteristics and Design: This study is a prospective, two-parallel-
arm, randomized pilot trial comparing Time Limited Eating (TLE) to a standard 12+hour eating window 
(Control). We will enroll 100 economically, ethnically, and racially diverse adolescents of all gender 
expressions,  diagnosed with type 2 diabetes (T2D), aged 13-21 years, with a BMI > 95th percentile from 
Children’s Hospital Los Angeles (CHLA, Los Angeles, CA). Randomization to the two groups (1:1 
allocation) will be blocked and stratified by age and sex. Participant allocation will be concealed from the 
study staff until after all randomization has occurred.  
i) Inclusion Criteria: Participants must meet all of the following criteria to be enrolled in the trial: 
(1) Age 13-21 years 
(2) Tanner stage III and above 
(3) Diagnosis of T2D based on the American Diabetes Association diagnostic guidelines 
(4) Hemoglobin A1c < 9% and on monotherapy with Metformin monotherapy (This criterion is based 
on the ADA and International Society for Pediatric and Adolescents Obesity recommendations for 
treatment of T2D in adolescents who receive insulin for HbA1c >9%. 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). 
(5) Participant and/or parent/guardian or family member must have a personal smartphone that is 
compatible with a continuous glucose monitor (CGM)  
(6) Willing and able to adhere to the assessments, visit schedules, and eating/fasting windows 
ii) Exclusion Criteria: Participants will not be eligible to participate if they meet any of the following 
criteria:  
(1) Previous diagnosis of Prader Willi Syndrome, brain tumor or hypothalamic obesity 
(2) Serious developmental or intellectual disability 
(3) Previous diagnosis 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 be in the imaging modality without sedation) 
(5) Previous or planned bariatric surgery 
(6) Current planned use of an anti-obesity or T2D medication (e.g. phentermine, topiramate, orlistat, 
glucagon like peptide-1 agonist, naltrexone, bupropion, SGLT-2 Inhibitor, etc.) or insulin 
(7) Current participation in other interventional weight loss studies.  
(8) Currently eats for less than 10 hours a day.  
iii) Inclusion of Women: We will enroll adolescents of all gender expressions,  diagnosed with T2D. We 
expect approximately 60% of the study participants will be female.  
iv) Inclusion of Minorities: The study site will make it possible to recruit an ethnically and racially 
diverse sample, with CHLA serving Latinx and Black adolescents. The anticipated racial and ethnic 
composition of the study reflects the T2D population at CHLA. 
v) Inclusion of Children: Children constitute the target population for this study as we aim to evaluate 
the impact of TLE on adolescents with T2D. In our experience, children younger than 13 years of age 
and older than 21 years would require different intervention/counseling strategies. Therefore, we can 
develop a more consistent “age-neutral” approach if we limit the age range to 13-21 years. In addition, 
based on our ongoing experience, this age range incorporates the general window of late pubertal 
development and we will limit recruitment to participants who are Tanner stage 3 or greater to exclude 
the potential confounding effects of early pubertal transition. Puberty will be determined by Tanner 
staging during examination by a physician and included as a co-variate. The IRB has strict regulations 
for the approach to and documenting of assent by minors and consent by their parents/guardians. 
Documentation of assent/consent is done via IRB-approved study-specific forms. 
2) Study Procedures, Materials, and Potential Risks: 
a) Study Clinical Sites: The study will be conducted at CHLA. The Clinical Trial Office (CTO) at CHLA will 
be the primary regulatory unit for the study, with oversight for human protection from the CHLA 
Institutional Review Board (IRB). The CHLA IRB will be the IRB of record. Data protection will be ensured 
by storing on an IS-approved university database on encrypted servers. All participants will be issued a 
study ID with data entered in de-identified manner. All databases will be password-protected with access 

only to the study team. All paper/documentation/research charts will be maintained in locked locations 
accessible only to the study team.  
b) Sources of Material. Data sources include questionnaires, blood samples, and anthropometric data. 
Privately identifiable information will therefore be collected. All data will be kept confidential and used 
only for research purposes. 
c) Questionnaires, and Medical Chart Abstractions. Participants will be asked to complete 
standard/validated questionnaires data using web-based (Research Electronic Data Capture, REDCap) 
or paper-based forms. Demographic variables include age, race, ethnicity, marital status, education, and 
income level. The baseline questionnaire will also ascertain data on a variety of potential risk factors, 
including family history, medical history, supplement use, medication use, and lifestyle factors. We will 
measure weight and height. Clinical variables will be extracted from medical records, i.e., date of 
diagnosis and treatment (start date and dose). NIH PROMIS short forms, validated in pediatric 
populations, will be used to assess symptoms of anxiety, and depression. For lifestyle behaviors, we 
focus on four activities of interest: (1) physical activity; (2) sleep; (3) dietary intake; and (4) attitudes 
towards food and eating because intermittent fasting could positively or negatively affect these areas. 
Diet intake will be assessed using 24-hour recalls, while attitudes around food and eating will be assessed 
using the Dutch Eating Behavior Questionnaire (DEBQ) and the Binge Eating Disorder Screener (BED-
S). Questionnaires will be used to measure sleep and physical activity. The Pittsburgh Sleep Quality 
Index (PSQI) and Munich ChronoType Questionnaire (MCQ) will be used to assess subjective sleep 
quality and disturbance. Assessments will be conducted at baseline, weeks 4, 8, and 12.   
d) Blood Collection: We will collect, process, and store blood according to standard protocols for the 
hemoglobin A1c, C-peptide, insulin, Insulin-Like Growth Factor (IGF-1), and glucose levels. Blood will be 
collected at onboarding and week 12 and stored at -70°C. 
e) Intervention Compensation: Each youth participant, regardless of the group they are assigned to, will 
receive compensation in the form of gift cards. Each youth participant will receive $50 at each study visit 
they attend (5 visits in total, for a total of $250 per participant). Parents/guardians/family members will 
also receive a $20 gift card for each study visit they attend for a total of $100 for participation in the study 
to account for time and effort required to support their participant. Parking validation will be provided. All 
families who do not have a car will be offered free ride-sharing transportation via UBER to- and from 
study visits upon request. 
f) Potential Risks/Adverse Events Monitoring and Procedures Used to Minimize the Risks: 
Participants will be queried about adverse events at each phone call and study visit and will additionally 
be instructed to report adverse events as they occur. Participants will be provided with (A) a phone 
number and email address to report non-urgent adverse events to the research coordinator; and (B) a 
phone number to directly reach the study physician, in case of serious adverse events. In addition, all 
participants will be provided with our diabetes hotline number. This hotline is covered 24 hours per day 
by rotating certified diabetes educators during the day and on-call endocrinologist at night. The study 
physicians will immediately refer participants to the appropriate medical care (e.g., urgent care or non-
urgent care) should any pressing concerns arise during the study period. In case of emergency, 
participants will be instructed to call 911 before calling the study physician. Should a participant require 
urgent or emergency care, the study physician will follow up with the participant’s healthcare provider to 
determine whether it is safe for the participant to continue in the trial. 
g) Adverse events will be subsequently documented and reported as described above. The severity of the 
event is graded as follows: 
i) Mild (Grade 1): the event causes discomfort without disruption of normal daily activities. 
ii) Moderate (Grade 2): the event causes discomfort that affects normal daily activities. 
iii) Severe (Grade 3): the event makes the patient unable to perform normal daily activities or significantly 
affects his/her clinical status. 
iv) Life-threatening (Grade 4): the patient is at risk of death at the time of the event. 
v) Fatal (Grade 5): the event causes death. 
h) Risks Related to Time Limited Eating (TLE): Adverse events are unlikely as a result of participation in 
this study. The PI, co-investigators, and study team will monitor participants for mild symptoms 
associated with TLE, such as thirst, headaches, and gastrointestinal issues, as well as the potential risk 
for significant weight loss or malnutrition. All participants are on Metformin and will complete a standard 
Metformin titration plan in which they will be instructed to increase the dose by 500 mg per week to a 
goal dose of 1000 mg twice daily. This titration plan will prevent gastrointestinal side effects. Participants 

will be instructed to take the medication with the first and last meal of the day during their eating window. 
At a minimum, the study staff will talk with study participants weekly to monitor for adverse events. To 
reduce the risks of increased thirst, headaches, and gastrointestinal issues, participants will be 
encouraged to stay hydrated by drinking water. Significant weight loss is defined as a 2% reduction in 
body weight in a week, a 5% change in one month or a 7.5% change within three months. Weight change 
will be closely monitored at every study visit to avoid triggering any hazardous medical conditions. In the 
event that a participant loses too much weight or loses weight too rapidly, the PI will counsel the 
participant and design a nutrition plan to increase daily caloric intake as needed.  
i) Attitudes and practices around food and eating: None is anticipated. We will continuously monitor for 
unforeseen or unanticipated events and risks. If a participant report unhealthy compensatory eating 
behavior (i.e., binge eating, excessive restraint, purging, etc.) during the weekly phone calls or research 
visits, we will refer them to their primary provider to have an official psychological evaluation. If we suspect 
that the adolescent is purging or placing themselves in immediate medical danger, we will contact their 
parent or guardian and create a safety plan and instruct them to go the local emergency room for 
evaluation. In addition, the PI will contact the primary care provider to ensure appropriate referrals for 
psychiatric support are obtained. Adolescents who experience psychiatric emergencies will be withdrawn 
from the study. Dr. Salvy is a clinical behavioral psychologist and will provide oversight, monitoring and 
guidance to the PI regarding the monitoring of any adverse events related to behavior changes that may 
occur during the study period.  
j) Progression of diabetes requiring escalation of care: The current International Society for Pediatric 
and Adolescents Diabetes (ISPAD) clinical practice guidelines for the management of T2D in adolescents 
recommend monotherapy with Metformin if the hemoglobin A1c (HbA1c) is < 9% and to escalate 
treatment should the HbA1c trends > 10%. To monitor glycemic control during the 12-week study period, 
all participants will wear a CGM. The study team will review the data weekly for each participant. If the 
data reveal average blood glucose levels > 240 mg/dL, consistent with an HbA1c level >10%, then the 
participant will be instructed to contact his/her primary endocrinologist to determine if insulin initiation is 
required. Participants who experience progression of their diabetes and require insulin initiation will be 
allowed to remain in the study.  
k) Risk associated with DEXA: The participants will be exposed to a small amount of radiation during their 
DEXA scan (radiation dose of 0.001 mSv), which is equivalent to 3 hours of natural background radiation 
and less than a coast-to coast round trip airline flight, which is about 0.03 mSv and poses minimal risk to 
the youth.  
l) Risk associated with MRI: MRI images are obtained without using any ionizing radiation; thus, 
participants will not be exposed to the harmful effects of radiation. There are very few known health 
concerns from temporary exposure to the MRI environment; however, the MR environment does involve 
strong, static magnetic fields that carry specific safety concerns including: may attract magnetic objects 
which could damage the scanner or injure the participants if those objects become projectile, loud 
knocking noises which may harm hearing if adequate ear protection is not used, enclosed space which 
could induce anxiety or feelings of claustrophobia, and peripheral muscle or nerve stimulation and 
overheating of the body.  
m) Risk associated with CGM use: There are risks for developing pain, bleeding, or burning at the insertion 
site of the CGM. In rare cases, there is a risk an infection may develop. There are risks of skin irritation 
to the adhesive tape. We have a process to address skin irritation, which involves evaluation by the PI 
with recommendations for topical treatments as needed, which may include over-the-counter 
hydrocortisone ointment or barrier creams.  
n) Risks Related to Blood Draws: A small minority of participants will likely experience transient 
discomfort, pain, bleeding, and/or bruising from the needle insertion and/or IV. This poses minimal risk. 
Infection is also possible in rare cases. This risk will be minimized by having trained nursing and 
phlebotomy staff use sterile techniques to draw blood. 
o) Psychological Risks: Though none of the questionnaires contain items that are particularly sensitive, 
personal, or potentially upsetting, it is possible that a participant may become upset thinking about some 
of the questions or topics in this study. Trained research coordinators will be conducting the assessments 
to address any potential incidents. All participants will be informed that they are free to refuse to answer 
any questions or questionnaires. They will also be informed that they can withdraw from the study at any 
time without penalty.  

p) Social Risks: Some participants in the TLE group may spend less time engaged with family and friends 
while eating and may feel socially disconnected. Social functioning will be monitored as part of the weekly 
phone calls. Social risks will be minimized by requiring that participants adhere to TLE an average of 6 
days per week (minimum of 5 days per week, 7 days prescribed). Dr. Salvy will also be available to 
counsel participants and help problem-solve social conflicts around meal-timing.  
q) Risks Related to Biohazards: All staff will follow the Code of Federal Regulations on the handling of 
biospecimens (29 CFR Part 1910-1030) and hazardous chemicals (29 CFR Part 1910-1450). Human 
biospecimens (serum blood collected to measure: HbA1c, C-Peptide, Insulin, and Glucose) will be 
collected by doctors, nurses, or other trained personnel, and the collected samples will be processed and 
analyzed by trained technicians. All blood samples and reagents will be handled in approved areas using 
established guidelines set by Children’s Hospital Los Angeles Occupational Health and Safety Offices. 
The collected blood specimens will be documented and stored in monitored and locked facilities. Blood, 
chemicals, and any materials that encounter biospecimens will be disposed of in designated biohazard 
waste receptacles, following federal and local biohazard regulations. All staff members who will encounter 
blood samples and chemical reagents are trained to safely handle these biospecimens and are retrained 
annually.  
r) Risks Related to Privacy and Confidentiality: To protect privacy, each study participant will be 
assigned a unique identification (ID) number. Data forms, participant information, and biological 
specimens will be coded using these ID numbers. Personal, identifiable information will not appear on 
these materials; instead, the key linking the participant’s identity to their unique identification number will 
be stored separately in a secure location. Records that identify study participants will be kept confidential 
as required by law, and every effort will be made to maintain the confidentiality of participants’ study 
records. Except when required by law or if necessary, to protect their rights or welfare, study participants 
will not be identified by name or any other identifying characteristics in records disclosed outside of the 
investigational team. To manage study data, we will use REDCap, a secure web application that meets 
both HIPAA and 21 CFR Part 11 requirements. REDCap leaves a pristine audit trail by documenting all 
changes to data, and data access is strictly controlled with password authentication and user controls. 
Data from the medical chart and clinical outcomes and adverse events will be electronically uploaded to 
the database, and all questionnaires will be coded into and administered through REDCap. Such 
electronically stored data will be protected through stringent security measures assured by Children’s 
Hospital Los Angeles technical departments and through the use of coded ID numbers and electronic 
security systems required by HIPAA. Paper documents will be scanned and saved on each site’s secure 
network and also stored in locked cabinets in locked offices. Biological specimens will be stored and 
analyzed in locked areas with restricted access. Access to participants’ data and biological specimens 
will be limited only to the study’s investigators, clinical support staff for this study, the overseers of clinical 
facilities, and the study sponsor—all on a need-to-know basis. The study team has significant experience 
with the operation of clinical trials and safeguarding confidentiality 
s) Trauma, Bullying, and Domestic Violence Risks: None anticipated. We will continuously monitor 
unforeseen or unanticipated events and risks. If trauma and/or domestic violence is suspected, either 
through completion of the questionnaires or through participants’ report or staff observation, we will 
implement the following procedures: (1) we will make participants aware of resources available to them 
in their communities, such as shelters; (2) we will work with participants to develop a safety plan for 
addressing violence and seeking shelter; and (3) we will ascertain risk to the child(ren) in the household. 
If we suspect that the child(ren) has/have been abused or witnessed domestic violence, we will report 
the incident to child protective services. Participants who are victims of domestic violence will be allowed 
to remain in the study if they wish to do so. 
t) Suicidal Behavior Risks: None anticipated. We will continuously monitor for unforeseen or 
unanticipated events and risks. We follow the Substance Abuse and Mental Health Services 
Administration SAFE-T: Suicide Assessment Five-Step Evaluation and Triage approach to determine risk 
and the appropriate clinical response. The five steps are Identify Risk Factors, Identify Protective Factors, 
Conduct Suicide Inquiry, Determine Risk Level/Intervention, and Document (which includes intervention 
and follow-up).  As per practice guidelines, we will estimate suicide risk as low, moderate, or high. All 
potentially suicidal participants will be given an emergency plan with numbers to call (e.g., local hospital 
emergency rooms, suicide hotlines, staff, and study physicians). Each plan will be individually tailored to 
the needs and resources of the participants. Family members will be incorporated into the plan. 

Adolescents who experience psychiatric emergencies such as suicidal behavior will be withdrawn from 
the study. 
u) Alternative Treatments: Participants will be informed that the alternative option is not to enroll in the trial 
and their decision whether to enroll will not affect the quality or extent of medical care that they receive. 
v) Handling Incidental Findings: If any clinically abnormal result or illness is uncovered, or if participants 
exhibit signs of depression or mental illness, the affected participant will be notified and referred to his/her 
physician or an appropriate health professional for treatment. Participants will be offered copies of any 
tests or incidental findings. 
w) Stopping Rules: The Data Safety Monitoring Board (DSMB) will stop the trial if there is sufficient 
evidence of harm from TLE, as determined by adverse event reporting and/or safety monitoring of 
malnutrition diagnoses, or in the unlikely event that it appears the study cannot be conducted 
successfully. If there are statistically significant cases of negative compensatory eating behaviors or 
negative mental health with a difference in rates between groups is >30%, then the trial will be stopped. 
These endpoints will be assessed on a quarterly basis by the independent safety monitors and Drs. 
Vidmar and Salvy, to monitor intervention fidelity. However, these possibilities are considered unlikely, 
given the low adverse event rate, evidence of benefits in our pilot studies. 
3) ADEQUACY OF PROTECTION AGAINST RISK 
a) Informed Consent: Participants will be recruited from Children’s Hospital Los Angeles (Los Angeles, 
CA). The typical approach will be through direct involvement with the treating physician. In their clinics, 
they will introduce the study to their patients and connect interested participants with the study staff. 
Research staff will carefully review the full consent form with the participant and parent or guardian in 
person or via phone, answering the participant’s questions about the study. Participants will be allowed 
to electronically sign consent forms online using DocuSign, REDCap, or printed forms in-person. 
Alternativley, research staff will review medical records of potential participants in order to identify 
participants who may be eligible. CHLA has natural language processing algorithms that allows for rapid 
searches of electronic medical records to identify patients with specified criteria for recruitment into 
studies. Research staff will first discuss potential participants with the PI and treating physician before 
making contact. After the initial recruitment process, a follow-up phone call will be made by a trained 
recruiter within one week to answer questions and solicit participation. Consent can be withdrawn from 
at any time. Potential participants will have the following carefully explained: (1) the investigational nature 
of the research; (2) the objectives of the research; (3) the procedures involved in the research; (4) any 
and all risks and discomforts due to participation; and (5) alternative options to participation that are 
currently available. Clarification questions will then be elicited from the potential participants and their 
parents/guardians. Only after the above will an IRB-approved document recording informed consent be 
signed as per institutional guidelines with a copy to be given to the participant and the original stored with 
the research record in a secure location.  
b) Protection Against Risk: 
i) Safety Reviews: The PI (Vidmar) and Primary Mentors (Goran, Raymond), and Advisory Committee 
(Salvy, Espinoza and Durazo-Arvizu) will review this protocol on a continuing basis for participant 
safety. The IRB will review this protocol on an annual basis for subject safety, and we will include 
results of the review in the annual progress reports submitted to NIH. The annual reports will include 
a list of adverse events and will address: (1) whether adverse event rates are consistent with pre-
study assumptions; (2) reasons for dropouts from the study; (3) whether all participants met entry 
criteria; and (4) whether continuation of the study is justified on the basis that additional data are 
needed to accomplish the stated aims of the study. 
ii) Monitoring plan: Data monitoring will focus on performance (participant follow-up and retention, 
participant privacy and confidentiality, protocol adherence, and data quality) and safety (adverse 
events and required action/response). The PI and Mentoring team will be responsible for the regular 
monitoring of data and safety issues and will maintain the record of any reported adverse events and 
other concerns. The study data safety and monitoring plan will entail several components, overseen 
by the PI: 
(1) All CHLA IRB policies and continuous reporting requirements will be followed in conducting the 
study. Any actions taken by the IRB as part of its continuing review will be immediately reported 
to the NIH. 
(2) The PI will implement procedures to ensure that each participant provides informed consent and 
that all data remain confidential. This will also include a rigorous data management protocol to 

optimize data entry, accuracy/checking, and retrieval. Data will be stored in password-protected 
files accessible only to the investigators and staff under their supervision. In the database, only 
an ID code number will identify subjects. A list linking names and other identifiers with their ID 
codes will be stored in a separate file with a separate password. All original paper surveys and 
case report forms will be stored in locked file cabinets. The PI will review all data collection forms 
for completeness and accuracy and for protocol compliance. In the case of a breach of 
confidentiality or other adverse event, the PI will report the event to the IRB and the appropriate 
NIH officials, and appropriate procedural changes will be implemented to prevent future breaches 
or adverse events.  
(3) An internal committee comprised of the PI, Mentoring team, and consultants will meet quarterly 
to assess participant recruitment, accrual, and retention; data quality and timeliness; participant 
risk versus benefit; and the development of external conditions that could potentially affect the 
study.  
(4) Data Safety Monitoring Board (DSMB):  Although this is an early-phase clinical trial, the study will 
nevertheless enlist an external DSMC.  A data monitoring plan has been filed with the DSMC and 
IRB at time of study submission for IRB consideration.  The DSMC will meet every 6 months and 
as needed to review study progress. Adherence to the protocol, Good Clinical Practices (GCP), 
and institutional policy will also be monitored by the DSMC. The safety monitor will also be 
responsible for: a) Reviewing and approving the protocol and consent documents; b) Providing 
input on protecting the safety of participants; c) Approving the data and safety monitoring plan; d) 
Considering any major changes to the protocol, consent, and data and safety monitoring plans 
after enrollment has started; e) Reviewing all adverse event data; f) Providing an independent, 
objective review of participant safety and study progress, in conjunction with the quarterly reports; 
g) Considering new findings that may affect participant safety or the ethics of the study; h) 
Stopping the trial, if merited 
(a) DSMB Members: 
(i) TBD: Pediatric endocrinologist (Potential candidates: Steven Mittelman, MD, PhD, 
Division Chief Pediatric Endocrinology, Mattel Children’s Hospital, University of California 
at Los Angeles, Los Angeles, CA; Omar Ali, MD, Pediatric Endocrinologist, Valley 
Children’s Hospital, Fresno, CA). 
(ii) TBD: Occupational therapist or psychologist (Potential candidates, Beth Pyatak, OTD, 
Associate Professor, Chan School of Occupational Therapy, University of Southern 
California, Los Angeles, CA). 
(iii) Brittany Belcher, PhD: Health Behaviors Researcher who conducts clinical research 
related to physical activity and sedentary behavior measurement, and their relationships 
with disease outcomes.  
(5) All personnel who will interact with subjects will receive training on adverse event reporting. In 
response to any adverse event, forms will be completed promptly and returned to the study 
physicians for review and implementation of an appropriate action plan.   
(6) Quarterly safety reports will begin with a brief statement of the purpose of the study and a 
summary of the study design, including an organizational chart of all study personnel, as well as 
the projected timetable and targeted numbers for participant recruitment, intervention, and 
assessment. The study progress will be summarized, including enrollment, status, and retention 
of each cohort. In addition, a cumulative summary of the demographic breakdown of the sample 
will be summarized. Interim analyses will then be summarized. We will provide a detailed 
summary of any SAEs that have occurred since the previous Safety Report, including the 
participant name, nature of the event, date reported, action taken, resolution or ongoing 
complication(s) from the serious event, and whether the serious event was likely or unlikely 
related to participation in the study. In addition, any major issues or problems encountered, and 
steps taken to correct or address them will be summarized. Finally, in the latter stages of the study 
when it becomes relevant, the Safety Reports will also include a study summary, including a 
summary of the main findings, and procedures for preparing a report of study findings. Interim 
analyses of change in weight will be conducted, and the results summarized in the Safety Report. 
4) POTENTIAL BENEFITS OF THE PROPOSED RESEARCH TO HUMAN SUBJECTS AND OTHERS 
a) Benefits to Individual: 

i) Potential benefits of the proposed research to human participants and others: This study will help 
researchers and professionals understand how TLE impacts β-cell function and body composition in 
adolescents with T2D with the potential that the intervention will improve glycemic control and delay 
disease progression. Thus, the benefits of this project to the individual and society greatly outweigh 
the risks. 
ii) Importance of the knowledge to be gained: Research participants may expect benefits from learning 
about their health. All participants will be offered copies of test results from procedures performed 
during the study. In the case of an abnormal test result of other incidental finding, participants will be 
instructed to visit their physician or other appropriate health care providers. Finally, participants may 
benefit from better understanding nutritional strategies. Overall, this clinical trial may inform future 
interventions for adolescents with T2D.  
iii) Risk-to-benefit ratio: As the known risks to participants from the intervention (i.e., increased thirst, 
headaches, gastrointestinal issues) and procedures like blood draws (e.g., bruising, temporary pain) 
are minor, we believe that these benefits outweigh the risks, as the risks to participants are minimal 
and will be monitored by regularly assessing participant safety 
5) CLINICAL TRIALS REGISTRATION: This trial is currently registered at clinicaltrials.gov with the identifier 
NCT04536480 
 
 

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Crose A, Alvear A, Singroy S, Wang Q, Manoogian E, Panda S et al. Time-restricted eating improves quality of 
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CHILDREN’S HOSPITAL LOS ANGELES 
INFORMED CONSENT/PARENTAL PERMISSION/ASSENT TO PARTICIPATE IN A RESEARCH STUDY 
 
 
 
Subject’s 
Name: 
 
 
 
 
     Birth 
Date:  
 
  
 
 
CHLA MRN#  
 
 
 
 
 
 
A person who takes part in a research study is called a research subject or research participant. If you are 
reading this consent form as a parent/legal guardian, “you” also refers to “your child” (the research 
participant) and/or the research participant, as applicable. 
 
KEY INFORMATION  
You are being asked to participate in a research study. This section describes the key information that we 
believe most people need to decide whether to take part in this research. Later sections of this document will 
provide the details of the research.  
 
What should I know about this research? 
• Taking part in this research is voluntary. Whether you take part is up to you. 
• If you don’t want to take part, it won’t be held against you. 
• You can take part now and later drop out, and it won’t be held against you. 
• If you don’t understand, ask the research team questions. 
• Ask all the questions you want before you decide. 
 
How long will I be in this research? 
Participation will last up to 16 weeks. 
 
Why is this research being done? 
This research is being done to find the effectiveness of a diet plan (Time Limited Eating or TLE) on glycemic 
control, β-cell function, body fat and body mass index (BMI) in adolescents with Type 2 Diabetes (T2D). 
 
What happens to me if I agree to take part in this research?  
Study procedures for this research are:  
• You will be randomized into 1 of 2 groups.  
o Group 1: Non-TLE (Non Time Limited Eating) - 12-hour or more eating window without 
mealtime restrictions 
o Group 2: TLE (Time Limited Eating) – 8-hour eating window 7 days per week 
• You will attend 5 visits at CHLA and have follow-up phone calls. 
• You will be trained and wear a continuous glucose monitor every day for 12 weeks. 
• You will have weight and height measured, research blood draws and Mixed Meal Tolerance Testing.  
Research imaging which will include a DEXA and MRI scan will be done. 
• You will be asked to completing surveys. 
 
Could being in the research hurt me? 
The most important risks or discomforts that you may expect from taking part in the research are: 

• Feeling uncomfortable answering some of the questions. 
• Mild discomfort (pain), bruising and swelling where the needle is placed in your arm, and dizziness or 
fainting from blood draws. 
• Small radiation exposure from scans. 
• Headache or dizziness after not eating for prolonged periods if you’re in the time limited eating group.  
• Mild discomfort (pain), bruising or irritation at the insertion site from wearing a continuous glucose 
monitor.  
Please see the POSSIBLE RISKS AND DISCOMFORTS section below for a complete list of expected risks. 
 
Will being in this research benefit me? 
The most important benefits that you may expect from taking part in this research are:  
• Learning new skills for healthy eating and weight management. 
• Improving glycemic control. 
• Delaying disease progression. 
 
What other choices do I have besides taking part in this research? 
Instead of being in this study, your choices may include: 
• Get routine care or treatment for your condition. 
• Join another clinical research study. 
 
 
INTRODUCTION 
You are invited to join a research study led by Dr. Alaina Vidmar, MD from the Endocrinology Department at 
Children’s Hospital Los Angeles (CHLA).  The study is paid for by the Pediatric Endocrine Society. 
 
You are invited to join this study because you have Type-2 Diabetes. Participation in this study is voluntary. 
Please read the information below and ask questions about anything you do not understand before deciding 
whether or not to be in the study. 
 
PURPOSE OF THE STUDY  
This research is being done to find the effectiveness of a diet plan (Time Limited Eating or TLE) on glycemic 
control, β-cell function, body fat and body mass index (BMI) in adolescents with Type 2 Diabetes (T2D). 
 
NUMBER OF PARTICIPANTS 
Up to 100 adolescents and 100 family members will be invited to join the study at CHLA. 
 
LENGTH OF PARTICIPATION 
Participation in this research will last 16 weeks with up to 5 in-person study visits at CHLA. 
 
PROCEDURES 
If you volunteer to be in this study, we will ask you to do the following things:  
 
You will be randomized into 1 of 2 groups below. A computer program will randomly (like flipping a coin) 
assign you to one of the following groups after 1 week of wearing a continuous glucose monitor (CGM):  
 
Group 1: Non-TLE (Non Time Limited Eating) - 12-hour or more eating window without mealtime 
restrictions 
Group 2: TLE (Time Limited Eating) – 8-hour eating window 7 days per week 

 
During the research study you will be asked to do the following things (each of these items is specific for the 
research study and not considered standard of care for your condition): 
 
▪ Follow the dietary guidelines provided to you by the study team: 
o TLE (Group 2 only): only eat during an 8-hour window i.e.  11 AM – 7 PM 7 days per week.  
▪ Continuous glucose monitor (both groups): You will wear a continuous glucose monitor called the Dexcom 
G6 Mobile CGM system every day to monitor your blood sugar level. The study team will create a Dexcom 
research account on your behalf using a research email. The study team will review your blood sugar levels 
with you over the phone each week. We will provide you with the device to use for 12 weeks. You will be 
trained on the use of this device. The Dexcom app will be downloaded to your or family member’s 
personal smart phone. If you, your parent, legal guardian family member does not own a Dexcom 
compatible smart phone, you will use the Dexcom receiver. Please see appendix B for information about 
this device.  
▪ Phone Follow Up (both groups): A member of the research team will call you once a week to discuss any 
barriers you may be experiencing. These conversations will be audio-recorded for educational purposes 
and should last approximately 15-30 minutes. A code name of your choice will be used during these 
conversations.  
▪ Follow-up plan (both groups): At the end of the intervention, your participation in this study will be 
complete. 
 
In addition to the above, the following research procedures will be done to all subjects in both groups through 
the end of the study: 
▪ Weight and height checks: At every visit, we will weigh you and measure your height. This will be done in 
a private area. 
▪ Surveys: You will complete several surveys at every visit. These surveys collect information such as your 
eating behaviors, how well you cope with stress, and satisfaction with the intervention. Each survey will 
take approximately 5-10 minutes to complete. You also have the option of completing the surveys virtually 
via WebEx or over the phone.  
▪ Dietary Recall: You will complete a dietary recall of all the food and beverages you consumed over 2 days 
(48 hours) prior to the day of the visit. This will take approximately 45 minutes to complete and will occur 
at Visit 2 and 5. The dietary recalls will take place at your in-person visits or virtually via WebEx or over the 
phone. Daily Eating Log: You will complete eating logs every day. These logs will collect the time you 
started eating and the time you stopped eating each day for 16 weeks. A member of the research team 
will record your logs once a week. 
▪ Medical record review: If you are a patient at CHLA, as part of your regular care, you may have blood work 
done every year to evaluate for your health. We will review your medical record and collect the results of 
your blood work if they occurred in the last 8 weeks from the consent date. 
▪ Research blood draws (fasting blood tests are considered standard of care at baseline for anyone 
entering into a weight management program): Approximately 9 mL (2 teaspoon) of blood will be collected 
by sticking a needle in a vein of your arm for each blood draw. You will have to fast (not eat anything for at 
least 6 hours) before each blood draw. Blood draws will occur at visit 1 and 5. 
▪ Research images (during Onboarding [visit 1] and at day 84 [Visit 5]):  
o DEXA scan: this will take a picture of your entire body and will take 30 minutes to obtain the image. 
o MRI scan: this will take a picture of your entire body and will take 30 minutes to obtain the image. 
▪ Mixed Meal Tolerance Testing (during Onboarding [visit 1] and day 84 [Visit 5]): In preparation for the 
test, you will eat a high carbohydrate diet for the three days leading up to the test and fast the morning of 
the test. During the test, you will drink a liquid meal. You will have an IV placed in your arm and have a 

small blood sample drawn at 0, 60, 90, and 120 minutes after consuming the liquid meal. Approximately 9 
mL (2 teaspoons) of blood will be collected from the IV for mixed meal tolerance testing at each visit. 
 
FOR YOUR PARENT/GUARDIAN OR OTHER FAMILY MEMBER 
Your participation is optional if your child is over the age of 18 years.  
▪ Surveys: Your family member will be asked to complete several surveys. These surveys will collect 
information such as age, job, health insurance, and ethnicity. Each survey will take about 5-10 minutes to 
complete. Your parent/legal guardian or family member will spend approximately 1 hour completing 
surveys. They will have the option to complete at in person visits or virtually via WebEx or over the phone.  
▪ Weight and Height: Your family members’ height and weight will be measured.  
 
Your family member will need to travel to CHLA with you for your in-person study visits and/or to complete in 
person study procedures.  
 
RESULTS OF TESTS PERFORMED FOR THE STUDY 
The results of the following research tests and research information will be shared with you and your doctor 
upon request:  
• Lab Testing: hemoglobin A1c, glucose level, liver function tests (AST&ALT), insulin, lipid panel, c-
reactive protein (CRP), c-peptide, Insulin-Like Growth Factor (IGF-1) and mixed meal tolerance tests. 
• Research image studies – DEXA scans and MRI scans 
• Weight trends over the study period  
 
Any abnormal lab test results from this study will be sent to your doctor as they may be important to your 
safety.   
 
POSSIBLE RISKS AND DISCOMFORTS 
Surveys: You may feel uncomfortable answering some of the questions. You can choose to skip or stop 
answering questions at any time. Surveys that will be completed by you and your family member ask about 
anxiety and depression. If you report extreme anxiety, binge eating disorder, or depression, we will refer you 
to a healthcare provider for immediate evaluation and a referral for mental health services if appropriate. This 
may result in additional costs to you if you require additional procedures, tests and/or treatments as 
determined by your healthcare providers.  
 
Research blood draws: Having blood taken may cause pain, swelling, bruising, redness, and/or minor bleeding 
at the site of the needle stick. In rare cases, an infection or small blood clot may happen. 
 
Imaging:  
Risk associated with DEXA: You will be exposed to a small amount of radiation during your DEXA scan 
(radiation dose of 0.001 mSv) which is equivalent to 3 hours of natural background radiation and less 
than a coast-to-coast round trip airline flight which is about 0.03 mSv and poses minimal risk. 
Risks associated with MRI: There are no known risks of physical harm associated with MRI. However, 
MRI machines produce loud banging noises, which cause some people to become stressed or upset. 
You may also feel uncomfortable inside the magnet if you do not like to be inside small places or have 
difficulty lying still.  The MRI magnet is always on and attracts certain metal objects. Any metal objects 
on or inside of your body may heat up, move, and/or not function properly within the scanning room. 
Metal objects in the room can fly through the air toward the magnet and hit those nearby. There are 
many safety measures in place to reduce these risks. The staff will screen all persons and materials 
entering the scanning room for metal. When the study begins, the door to the room will be closed to 
minimize the risk of someone accidentally bringing a metal object into the scanner room. 

Unexpected (incidental) Findings: It is possible that unexpected findings may be discovered from the 
research DEXA or MRI which you may find upsetting. You will be notified by the principal investigator if 
any unexpected findings are discovered. The principal investigator will advise you as to the nature of 
the findings and provide recommendations regarding appropriate follow-up with your physician. These 
findings may result in the need for you to have additional procedures, testing, and/or treatments as 
determined by your physician. This may result in additional costs to you and/or your health insurance. 
 
Time Limited Eating: There are risks and discomforts associated with calorie restricted diet, such as hunger, 
anxiety, drowsiness, dizziness, headache, muscle aches, fatigue, low blood pressure and, in rare cases, 
fainting. These diet interventions may also cause abnormal heart rhythms, short-term nutrient deficiency, and 
a weakened immune response.  
 
Continuous Glucose Monitor: While wearing the Continuous Glucose Monitor, you are at risk for developing 
pain, bleeding, or burning at the insertion site. In rare cases, an infection may develop.  
 
Psychological risks: It is possible that you may become upset thinking about some of the questions or topics in 
this study.  
 
Bullying or violence: If we suspect that you are a victim of bullying or violence at home or in your 
neighborhood, either through completion of the questionnaires, we will implement the following procedures: 
1) we will make you are aware of resources available in your community; 2) we will work with you to develop 
a safety plan for addressing bullying or violence; 3) we will ascertain the risk to you. If we suspect that you 
have been abused or witnessed domestic violence, we will make a report to child protective services. 
Children/adolescents who are victims of bullying or domestic violence will not be dropped from the study, 
unless they ask to drop out.  
 
Suicidal Behavior: If we suspect that you are suicidal, we will follow the Substance Abuse and Mental Health 
Services Administration SAFE-T: Suicide Assessment Five-Step Evaluation and Triage approach to determining 
risk and clinical response. The five steps are Identify Risk Factors, Identify Protective Factors, Conduct Suicide 
Inquiry, Determine Risk Level/Intervention, and Document (which includes intervention and follow-up).  
Adolescents who experience psychiatric emergencies such as suicidal behavior will not be dropped from the 
study, unless they request to terminate their participation.  
 
Binge Eating Behavior: If we suspect that you are developing any binge eating behaviors either assessed in the 
screening questionnaires or reported by you to a research staff during a weekly phone meeting, we will 
implement the following procedure: (1) we will make you aware of resources available in your community, (2) 
we will encourage you to contact your primary care physician for an evaluation and determination is 
psychiatric referral is warranted, (3) we will ascertain risk to you and (4) the PI will contact your primary care 
provider to ensure you receive the appropriate evaluation and referrals for treatment. If we suspect that you 
are purging or placing yourself in immediate medical danger, we will contact your parent or guardian and 
instruct you to go the local emergency room for evaluation. 
 
Mixed Meal Tolerance Test: You may experience discomfort with the IV placement or blood draw which 
should resolved with rest and laying down. You may experience dizziness, nausea, lightheadedness during the 
test.  
 
Privacy Risks (for both youth and the parent/legal guardian/family member subjects): As this study involves 
the use of your identifiable, personal information, there is a chance that a loss of confidentiality may occur. 

The researchers have procedures in place to lessen the possibility of this happening (see the CONFIDENTIALITY 
section below for details). 
 
There may be additional risks to participation in this research that we do not know about and therefore 
cannot describe. 
 
POSSIBLE BENEFITS TO SUBJECTS 
You may benefit from participating in this study by 
• learning new skills for healthy eating and weight management. 
• improving glycemic control. 
• delaying disease progression. 
 
Your parent/legal guardian/family member will not have direct benefits from participating in this study. 
 
POSSIBLE BENEFITS TO SOCIETY 
Your participation in this study may allow us to learn more about how adolescents can lose weight and 
develop healthier eating habits in the future by limiting the time during the day in which they eat. Hopefully 
this information will help in the treatment of future patients with obesity and Type-2 Diabetes. 
 
YOUR OPTIONS IF YOU CHOOSE NOT TO BE IN THIS STUDY 
The alternative to being in this research is to get the standard of care. The standard of care is to receive care 
at a multi-disciplinary weight management clinic which includes meeting with several doctors to develop a 
weight loss program and techniques to help you lose weight and maintain your weight loss. You can also 
choose not to participate in this study.  
 
COSTS TO YOU FOR BEING IN THIS STUDY 
Participants and their families are not responsible for any of the costs involved in this study.  The CGM will be 
provided to you at no cost while you take part in the study.  Neither you nor your insurance company will be 
billed for your participation in this research. However, participants will continue to be responsible for their 
phone and service plans. 
 
Parking validation will be provided on an as needed basis, upon request. All families who do not have a car will 
be offered ride share options (UBER or Lyft) for travel to and from CHLA for the study visits. 
 
RESEARCH INJURY  
If you think you have been hurt by taking part in this study, tell the doctor in charge of this research study as 
soon as possible. The research doctor’s name and phone number are provided in this consent form. CHLA will 
offer you the care needed to treat injuries directly resulting from taking part in this research. This care will be 
billed to you or your insurance company. You will be responsible for deductible and co-payments, or any costs 
not paid by your insurer.  
 
CONFIDENTIALITY 
The telephone sessions will be audio-recorded; therefore, the audio-recordings are considered “directly 
identifiable” since they will contain your voice. The audio-recordings will be kept in a secure location and only 
the research team will have access to them. These recordings will be listened to by people on the research 
team.  
 

If audio recordings of you will be used for educational purposes, your identity will be protected or disguised. 
The recordings will be listened to at 1.5 times speed to disguise the voices. You have the right to review the 
tapes if you desire.  
 
The data collected as part of this study will be “coded.” Coded means that the data collected for this study will 
be assigned a unique code or Study ID. Your research data will not include your name or any other identifying 
information about you. The code that could be linked back to your identifying information will be kept separate 
from your research data and specimens.  Only the members of the study team will be able to see the link or the 
information that can identify you. 
 
People on the research team and your doctors and nurses will know that you are in this research study. All 
results will be kept confidential. 
 
You will be asked to sign a separate form authorizing access, use, creation, or disclosure of health information 
about you. Your private information, data and medical records will be shared with individuals and organizations 
that oversee this research, including: 
• Government agencies, such as the Food and Drug Administration (FDA), and the Department of Health 
and Human Services. 
• Pediatric Endocrine Society 
• The CHLA Institutional Review Board (IRB) that reviewed this research, and authorized representatives 
of CHLA. 
 
Because this study involves medical procedures, a copy of this consent form will be placed in your medical 
record. This will allow the doctors that are caring for you to obtain information about any medications and/or 
procedures you are receiving in the study and treat you appropriately. 
 
We will take steps to keep your personal information private, but we cannot guarantee complete secrecy. All 
identifiable information about you will be replaced with a unique code or study ID. A list linking the code and 
your identifiable information will be kept separate from the research data. All research data and records will 
be stored electronically on a secure network with encryption and password protection to help prevent 
unauthorized access to your personal information.  
 
We will not release information about you to others not listed above, unless required or permitted by law. For 
instance: 
• if we learn of child or elder abuse, harm to self or others, or  
• if you have certain infectious diseases; or  
• you are injured and need emergency care. 
 
The results of the research may be presented or published. We will keep your name and other identifying 
information confidential. 
 
FUTURE RESEARCH USE OF DATA AND/OR SPECIMENS  
The data and specimens collected as part of this study will not be used for future research, even if all 
identifiers are removed. 
 
STUDY WITHDRAWAL 

The researchers may end your participation in this study for a number of reasons, such as if your safety and 
welfare are at risk, if you do not follow instructions or if you miss scheduled visits. The researchers might also 
decide to stop the study at any time. 
 
If you decide to stop being in the study, or are removed from the study, or the study is stopped, the 
data/specimens collected before you leave will be used but no more data will be collected. 
 
QUESTIONS ABOUT THE STUDY  
If you have questions, concerns, or complaints about the study, or think this research has hurt you or made 
you sick, talk to the CHLA research team: 
 
Daytime, Monday through Friday, 8:00 A.M. through 4:30 P.M. you may call the CHLA Principal Investigator, 
Dr. Alaina Vidmar at 323-361-3385. 
 
Evenings, nights, weekends or holidays you may call the hospital number, (323) 660-2450 and ask for the 
Endocrinology Service doctor on-call. 
 
ClinicalTrials.gov is a Web site that provides information about federally and privately supported clinical trials. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This 
Web site will not include information that can identify you. At most, the Web site will include a summary of the 
results. You can search this Web site at any time. 
 
This research is being overseen by the CHLA Institutional Review Board (“IRB”). An IRB is a group of people who 
perform ethical review of research studies. You may talk to them at (323) 361-2265, or hspp@chla.usc.edu if: 
• You have questions, concerns, or complaints that are not being answered by the research team. 
• You are not getting answers from the research team. 
• You cannot reach the research team. 
• You want to talk to someone else about the research. 
• You have questions about your rights as a research subject. 
 
FINANCIAL INTEREST OF THE INVESTIGATOR  
If your doctor is an investigator for this study, he/she is interested in both your healthcare and the conduct of 
this research.  You are not under any obligation to participate in a research study conducted by your doctor.  
 
RIGHTS OF RESEARCH SUBJECTS 
You can agree to take part in this study and stop your participation in the study anytime. You should not sign 
this form if you have any questions that have not been answered or if you are unclear about any information 
in this form.  
 
Your participation in the study is entirely voluntary. If you choose not to take part in the study or decide to 
stop your participation in this study at any time, there will be no penalty or loss of benefits to which you are 
otherwise entitled. If you wish to leave the study after agreeing to participate, you should let the Principal 
Investigator know. You are not under any obligation to participate in a research study conducted by your 
doctor. 
 
You will be told about any new information found during the course of the study that may affect your health, 
welfare, or choice to stay in the research. If this happens, you might be asked to sign a new consent form.  
 

• You have a right to have all of your questions answered before deciding whether to take part. 
• Your decision will not affect the medical care you receive from CHLA. 
• If you decide not to take part, you can still receive medical care from CHLA. 
• You will be given a copy of this signed and dated consent form and the “Experimental Subject’s Bill of Rights” 
to keep.  
• You will be asked to sign a separate CHLA HIPAA Research Authorization form authorizing the access, use, 
creation, and/or disclosure of your health information. 
 
SIGNATURE OF RESEARCH SUBJECT  
(For adults who are capable of providing consent; children ages 14 to 17 years old who are capable of 
providing assent) 
 
Your signature below indicates: 
• You have read this document and understand its meaning;  
• You have had a chance to ask questions and have had these questions answered to your satisfaction;  
• You consent/assent to your participation in this research study; and 
• You will be given a signed copy of this form. 
 
 
 
______________________________________________________________________ 
Print Name of Subject 
 
 
____________________________________    ________________________________ 
Signature of Subject  
 
 
 
Date 
 
SIGNATURE OF RESEARCH SUBJECT (PARENT/LEGAL GUARDIAN/FAMILY MEMBER)  
 
Your signature(s) below indicates: 
• You have read this document and understand its meaning;  
• You have had a chance to ask questions and have had these questions answered to your satisfaction;  
• You agree to your participation in this research study; and  
• You will be given a signed copy of this form. 
 
 
______________________________________________________________________ 
Print Name(s) of Subject  
 
 
____________________________________    ________________________________ 
Signature of Subject  
 
 
 
Date 
 
 
SIGNATURE OF PARENT(S)/LEGAL GUARDIAN(S)  
(For all subjects under the age of 18) 
 
Your signature(s) below indicates: 

• You have read this document and understand its meaning;  
• You have had a chance to ask questions and have had these questions answered to your satisfaction;  
• You agree to your child’s participation in this research study; and 
• You will be given a signed copy of this form. 
 
________________________________    ____________________________________ 
Print Name(s) of Parent(s)/Legal Guardian(s)  
 
____________________________________    ________________________________ 
Signature of Parent/Legal Guardian  
 
Date 
 
 
____________________________________    ________________________________ 
Signature of Parent/Legal Guardian  
 
Date 
 
SIGNATURE OF INDIVIDUAL OBTAINING CONSENT 
I have explained the research to the subject and/or the subject’s parent(s)/legal guardian(s) and have 
answered all of their questions. I believe that they understand all of the information described in this 
document and freely give consent/permission/assent to participate. 
 
______________________________________________________________________ 
Print Name of Individual Obtaining Consent 
 
 
____________________________________    ________________________________ 
Signature of Individual Obtaining Consent 
 
Date 
 
SIGNATURE OF WITNESS (if applicable) 
Your signature below indicates: 
• You were present for the entire consent conference. 
• The information in the consent document and any other written information was accurately explained 
to the subject and/or the subject’s parent(s)  
• The subject and/or the subject’s parent(s)/legal guardian(s) had an opportunity to ask questions and 
those questions were answered; and 
• The subject and/or the subject’s parent(s)/legal guardian(s) voluntarily signed the 
consent/permission/assent form in your presence. 
 
 
______________________________________________________________________ 
Print Name of Witness 
 
 
____________________________________    ________________________________ 
Signature of Witness  
 
 
 
Date