Supporting Parents of Young Children With Type 1 Diabetes in Closed-Loop System
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Sponsor: Stanford University

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Supporting Parents of Young Children with Type 1 Diabetes in Closed-Loop System 
Version 1.2 
October 27, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Synopsis of study protocol 
This is study seeks to evaluate interventions to improve glucose control and adherence of young 
children and their families using a hybrid closed loop system in the home environment throughout the 
day and night.   
 
We will enroll patients who are in the follow-up/continuation phase of the IRB and FDA approved 
Medtronic CEP302 study (IDE# G150247, NCT02660827). Subjects in this study are using the Medtronic 
670G hybrid closed loop insulin delivery system, but have completed the trial period of the protocol. 
 
This protocol is the addition of an educational/behavioral intervention(described below) designed to 
optimize their use of the hybrid closed loop system for their diabetes control. This is not a device 
intervention, and no IDE is required (since all subjects aree enrolled in the Medtornic CEP302 study).  
 
This adaptive study design employs the possibility of subsequent randomizations if pre-designated 
targets are not reached. All participants will be ages 2-6 years old and in the continuation phase of 
the Medtronic CEP 302 Trial using the Medtronic MiniMed 670G pump with Guardian 3 sensor.  All 
subjects will receive the same standardized education on using the pump with hybrid closed loop 
capabilities and continuous glucose monitoring (CGM) during the initial Medtronic CEP 302 trial 
phase.  A review session will also take place as they enter the extension phase of the study which is 
the beginning of this study. Their uploaded data will be reviewed every two weeks and if they are not 
meeting adherence (≥ 70% of the time in closed-loop) and glycemic target goals (≥ 65% of sensor 
values between 70 - 180 mg/dL), they will be randomized to six interventions: 1) reduce psychological 
distress, 2) reduce worries about hypoglycemia, 3) education and understanding of developmental 
and technologic demands for using hybrid closed loop this age group, 4) understanding and 
modification of carbohydrate to insulin ratios, set point and in depth nutritional education, and 
interventions 5) and 6) will be minimal interventions with a text message providing information on how 
they are doing at meeting their targets.  All these interventions will be compared to a minimal 
intervention (text of their results compared to target goals). We will examine group differences over a 
3-month period on health and psychological outcomes at baseline and after three months. 
 
Objectives:  The objective of this study is to assess several remote interventions with families in the 
extension phase of the 670G toddler study to determine which interventions are most effective in 
improving their time in target (70-180 mg/dl) and their adherence in maintaining closed-loop control 
(at least 70% of the time in closed-loop). 
 
Sample Size:   
• We anticipate enrolling at least 4 subjects at each of the current sites, and would like to 
expand the number of sites to include Yale, and the University of South Florida.   Each of 
these sites is scheduled to enroll at least 4 toddlers, and some will enroll up to 8.  We therefore 
anticipate being able to enroll at least 30 subjects.  A sample size of 26 subjects should allow 
for a statistically significant result with a power of 0.9 and a p of 0.05.  Enrollment of 30 
subjects would allow for a 10% drop out rate.  See Biostatistics and Data Analysis section. 
 
Sample size and power calculations were conducted with consideration of a clinically 
meaningful change in the primary outcome – percent time in target range – and the feasibility of 
enrolling participants from the continuation phase of the 670G trial. Each site has the potential to 
enroll up to 8 toddlers, and we expect that 70 to 80% would opt for the continuation phase and to be 
enrolled in the proposed study.   

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The primary outcome is the percent change in the amount of time spent in the target glucose 
range from baseline (prior to automated glucose control) to study completion. Data from our CGM 
study with toddlers (NIDDK funded DP3; Buckingham PI) show that of the sixteen 2-6 year-olds in the 
study, they achieve on average only 45% time in 70-180 mg/dL target range (standard deviation = 
15%). Our hypothesized change will be a 10% improvement in time spent in target range. There is 
sufficient power) to detect this change in a sample size of 26. Another aspect of calculating power in 
this study is the actual number of participants exposed to the planned interventions after a glucose 
“failure.” Over 90% of the participants in our DP3 toddler study experienced a glucose failure of less 
than 60% time in target range. Further, the table below shows the results of glucose failures from the 
DirectNet cohort of toddlers using CGM (Ped Diabetes 13:301-7, 2012).  
 
Table 1.  Expected Failure Rates 
 
Months 
 
0 
1 
2 
3 
4 
5 
6 
 
 
 
 
 
 
 
 
Glucose Failure (not having at 
least 65% of readings in the 70-
180 mg/dL range) 
- 
70% 
70% 
70% 
70% 
75% 
75% 
 
Study Procedures 
 
Participants will be recruited at 5 centers: Stanford University, the Barbara Davis Center for Diabetes, 
University of Colorado (referred to as Denver), Yale University, Indiana University, and University of 
South Florida. We expect to enroll 40 families total and attempt to have roughly equal enrollment at 
each site (ie. 4 to 8 at each site). Only families who have completed the Medtronic CEP 302 Trial and 
opt to participate in the continuation phase will be eligible for this study. Study staff will approach 
potential participants to explain the study, determine eligibility, and obtain informed consent.  
 
The study design is adaptive, specifically a SMART (sequential multiple assignment randomization 
trial). A SMART is an adaptive study design that allows for multiple assessments and based on the 
results of those assessments, a menu of interventions can be deployed. To ensure that there is no 
bias when interventions are delivered, and to have a test of whether those who receive the 
intervention fare better (or worse) from those who do not receive the intervention, a randomization 
strategy is used. The decision to use a SMART was primarily made because this is what happens 
clinically – a child (and family) start on a system with a certain dose of education and when problems 
arise, the clinical team offers interventions to optimize their use of the system. The SMART allows us 
to test which interventions are best for this patient population that presents many unique challenges 
for diabetes management and coordinated care from the team. 
  
 
All participants will complete a checkpoint visit every 2 weeks for the duration of 3 months. At each 
checkpoint in the study (weeks 2, 4, 6, 8, and 10), data from the preceding 2 weeks will be reviewed 
to determine if there have been “failures.” Data will be available through pump uploads and by asking 
caregiver participants the frequency of wearing the devices. Objective data will guide determination of 
failures. We are defining failure in the following ways:  
 
1) Adherence Failure:  defined as using the hybrid closed loop “Auto Mode” less than 70% 
during a week 
2) Glucose Failure:  defined as less than 65% time spent in glucose range of 70 - 180 mg/dL.  
 
If subjects pass both the adherence and glucose targets, no intervention is required. If there is an 
Adherence Failure, they will be eligible for an adherence intervention. The adherence interventions 

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will be randomized by order and the sequence of interventions will depend on whether a previous 
intervention has been administered. The participant may receive a minimum of zero adherence 
interventions over the 3 month period to a maximum of 5 adherence interventions during the 3 month 
period. A similar sequence of interventions will occur if patients experience a Glucose Failure. Finally, 
if subjects have both an Adherence Failure and a Glucose Failure at a checkpoint, they will enter the 
adherence intervention pathway. They will continue on this path until they have completed all three 
possible interventions. After this time, if they continue to failure both adherence and glucose targets, 
they will enter the glucose target intervention pathway. We decided that an adherence failure trumps 
a glucose failure because using the Auto Mode function is critical to opening the door to achieving 
glucose targets.  
 
The figure below shows the possibilities at each 2-week checkpoint. 
 
Figure 1.  Potential interventions at 2 week monthly visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 1 above graphically depicts the treatment scheme for participants in the SMART. Below, the 
conditions and possible scenarios are described in more detail. As a reminder, there are five 
checkpoints (2, 4, 6, 8, and 10 weeks). At each checkpoint, here are the possible scenarios. A = 
adherence; G = glucose range; and R = randomization below: 
 
1. If 1st A failure, R to A1, A2, or A3 
2. If 2nd A failure (ie., there was a previous A failure), and a history of A3, R to A1 or A2 
3. If 2nd A failure, with history of (respectively) A1(A2) give A2(A1). 
4. If A success, 1st G failure, R to G1,G2,G3 
5. If A success, 2nd G failure, w/ history of G3, R to G1,G2 
6. If A success, 2nd G failure, w/history of (respectively) G1(G2) give G2(G1). 
7. All else, no treatment. 
 
As noted above, an Adherence Failure is defined as use of Auto Mode for less than 70% of the time 
at a checkpoint. A Glucose Failure is defined as spending less than 65% of the time in the 70 - 180 
mg/dL range at a checkpoint. Also note that the final visit at 3 months is the end of the study and no 
interventions are offered at that study visit. 
PASS 
A1 – Developmental & Technological Demands intervention 
No intervention 
A2 – Reducing Distress intervention 
A3 – Minimal intervention 
G1 – Nutrition, set point, & carb/insulin ratio intervention 
G2 - Hypoglycemia management intervention 
G3 – Minimal intervention 
FAIL 
Adherence Failure 
Glucose Failure 

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Study Group 
 
All participants will be using the Medtronic MiniMed 670G pump with Guardian 3 continuous glucose 
monitor. All participants will be given the same systematic review on the use of these devices and 
hybrid closed loop function. This review session will take approximately 30 minutes. A person trained 
in delivering education about this pump and sensor will deliver the education at the first visit. This 
individual will be available to assist with questions from participating families.  
 
Behavioral Interventions 
 
The table below lists the interventions, their targets, and how each intervention will be utilized as 
supports for parents of young children with T1D using diabetes devices. Of note, these interventions 
are delivered when there are adherence or glucose failures and are intended to be delivered online or 
over the phone. 
 
Intervention Name 
Intervention Goal 
Frequency / Dose 
Interventionist 
Developmental & 
Technological 
Demands 
Provide education on using 
diabetes technology in various 
settings and formats in this age 
group, and increase ability for real-
time problem-solving. Identify and 
troubleshoot barriers to keeping 
young children in Auto Mode 
Two ≤30 minute 
sessions delivered 
over a one-week 
period.  
CDE, medical personnel, or psychologist on 
study team, with advanced training on the use 
of the Medtronic 670G pump and experience 
in diabetes, behavior, young children, and 
parenting.  
Distress Reduction 
Identify and reduce parent distress 
symptoms and worries. Provide 
strategies for obtaining social 
support. 
Two ≤30 minute 
sessions delivered 
over a oneweek 
period. 
PHD psychologist with advanced training and 
experience in diabetes, behavior, young 
children, and parenting.  
Nutrition, Set Point, 
& Carb/Insulin Ratio 
Provide education on a variety of 
properties of food and how they 
affect blood glucose levels. 
Optimize the use of carbohydrate 
to Insulin ratios, insulin duration of 
action, and use of temporary 
target glucose set point in the 
670G pump and the Quick bolus 
feature to gain better glycemic 
control 
Two ≤30 minute 
sessions delivered 
over a one-week 
period. 
CDE or medical personnel with advanced 
training in nutrition, diabetes and experience in 
the use of the Medtronic MiniMed 670G pump. 
Hypoglycemia 
management 
Focus on  hypoglycemia 
management to avoid 
hyperglycemia, review fear of 
hypoglycemia 
Two ≤30 minute 
sessions delivered 
over a one-week 
period. 
CDE, medical personnel, or psychologist on 
study team, with advanced training and 
experience in diabetes, behavior, young 
children, and parenting.  
Minimal Intervention 
A short communication detailing 
the percentage of time spent in 
range and in Auto Mode and if the 
goals have been met  
An email or text 
message sent 
weekly during the 
two-week period 
CDE or medical personnel on study team  
 
 
Optimize Adherence Interventions 
 
Below are brief descriptions of the interventions. 
 
Developmental and Technological Demands Intervention   

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There are no existing interventions that target the uptake and promotion of diabetes technology for 
parents of young children with T1D. Further, no interventions provide education and skill-building on 
how to use these devices and technologies across multiple settings (e.g., school, home, social 
activities) and by multiple formats (e.g., direct monitoring vs. remote monitoring). Becoming more 
comfortable with using these devices (specifically the Medtronic 670G pump and Guardian 3 sensor) 
in multiple settings should help to promote adherence to device use. We will continue to take 
advantage of several important themes. First, those individuals with more comfort with technology in 
general (e.g., smartphones and computers), are more comfortable and better equipped when using 
specific technology for managing health. Second, mobile technologies (apps and text messaging, for 
example) and programs that support the use of diabetes technologies are effective in increasing 
adherence to management tasks. The third theme and necessary component of this intervention will 
be to teach a brief 3-step rubric for solving problems: 1) identify the problem, 2) chose a solution 
decided on by the parent and interventionist, and 3) monitor for results at the next session. These 
sessions will specifically address some of the difficulties with keeping a child in Auto Mode. They will 
cover the most common reasons for getting kicked out of Auto Mode and discuss strategies to 
maximize the time spent in Auto Mode. The Developmental and Technological Demands intervention 
will include two ≈30-minute sessions.  
 
Distress Reduction Intervention 
 
 
Many parents of young children with T1D express worries, fears, concerns, and distress over many 
aspects of diabetes management. The Distress Reduction intervention targets 1) the identification of 
and reduction of parent anxiety/depressive symptoms (general and diabetes-specific) and 2) 
increasing access to and attainment of social support. It will also be delivered in two ≈30-minute 
sessions online (or over the phone if online is not available). Multi-media approaches will also be 
used in this session. We recognize this dose of an intervention is not intended to completely remove 
all parent fears and worries, nor will it fully connect them to a network of support. However, it is 
intended to reduce fears/worries and provide avenues for obtaining support that do enough to help 
them maintain adherence diabetes devices. 
 
 
Glucose Targets Interventions 
 
Below are brief descriptions of the interventions.  Each intervention will be recorded using Blue Jeans 
to capture the content delivered and duration of the intervention. 
 
Nutrition, Set point, and carbohydrate/Insulin Intervention and insulin duration of action 
 
These sessions will focus on how different factors affect blood glucose levels. Education on how 
combinations of proteins, fats and carbohydrates can be used to extend the release of glucose into 
the body will be discussed. We will also provide training on adjusting carbohydrate to insulin ratios to 
achieve better glycemic control. In addition we will address the target glucose set point of the 670G 
pump and how this can be changed during periods of activity to modulate insulin delivery. We will 
also review and potentially intervene with the duration of insulin action as an adjustable parameter to 
be either more aggressive or less aggressive with correction doses.  The duration of action can be 
modified to allow more aggressive correction bolus, or to decrease correction doses if there is a risk 
of hypoglycemia.  For young children for whom insulin is given immediately after eating (because the 
amount of food they will eat is unknown), the Quick bolus may be an option.  Each session will last up 
to 30 minutes and be delivered online or over the phone. 
 

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Issues with Hypoglycemia  
 
These sessions will primarily focus on parental concerns about hypoglycemia. In this age group we 
believe the major focus will be on fear of hypoglycemia, but we will also provide education and 
support on safely reducing hyperglycemia. Since many of these families may have previously used 
the Dexcom share with remote monitoring, we will discuss how they may or may not be using the 
Dexcom Share for remote monitoring since this feature is not available on the 670G pump.  We will 
review their fears and the child’s past severe hypoglycemic events, and what they have read and 
heard from friends and support groups. We will teach parents the links between fears/worries and 
diabetes behaviors (e.g., fear may lead to hyper vigilance which in turn causes more stress and 
burnout). We will provide behavioral strategies for monitoring for hypoglycemia (and hyperglycemia) 
at regular intervals, steps to problem solve unexpected high and low blood sugars, and basic efforts 
at sleep hygiene. These sessions have the same format (two ≈ 30-minute sessions delivered online 
or over the phone). 
 
Minimal Intervention 
 
The randomization to minimal intervention will be present in both the Adherence arm and Glucose 
arm. In this intervention the parent will receive either an email or text message that details what 
percentage of the prior two weeks spent in Auto Mode, percentage of time below, within, or above 
target glucose range, and whether they met the study goals for these areas.  If they have concerns 
about their management, they are of course instructed to contact their study coordinator or study PI.   
    
 
 
Study Visits and Measurements   
 
In person study visits for all participants will occur at baseline (0 weeks) and 12 weeks. These are the 
pre and post assessments that include all measures in table 2 below. Briefer assessments (or 
checkpoints) are completed at 2 weeks intervals. These visits should be within ±1 week of the 
scheduled visit. Any behavioral interventions delivered will be done remotely and will not require an 
in-person visit. All of the questionnaires will be completed online via RedCap. 
 
Table 2. Timeline and Components of Study Visits and Checkpoints  
Visit/Checkpoint 
1 
2 
3 
4 
5 
6 
7 
Study Time: 
0 
2w 
4w 
6w 
8w 
10w 
12w 
In-person or remote 
In-person Phone Phone Phone Phone Phone In-person 
History (medical and 
demographic) 
X 
 
 
 
 
 
 
Review of using 
Medtronic MiniMed 
670G pump and 
Guardian 3 Sensor  
X 
 
 
 
 
 
X 
Adverse Events such 
as severe 
hypoglycemia 
 
X 
X 
X 
X 
X 
X 
670G uploads  
X 
X 
X 
X 
X 
X 
X 
HbA1c 
X 
 
 
 
 
 
X 
Full Psychosocial 
Questionnaires 
X 
 
 
 
 
 
X 

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Checkpoint for 
Adherence and 
Glucose Failures 
 
X 
X 
X 
X 
X 
X 
Table 3. Assessment battery completed by Parents 
Measure 
Construct Measured / Relevant Points 
Number of Items / 
Time to Complete 
Psychosocial Outcomes 
Parents’ Diabetes 
Distress 
The Problem Areas in Diabetes, Pediatric 
version (PAID-P).  The PAID-P is a validated 
tool used to assess parental burden related 
to diabetes management. 
The Parent Diabetes Distress Scale (PDDS).  
This is a validated tool to assess how 
diabetes care impacts on parents’ quality of 
life.   
18 items. 5-10 
minutes to complete. 
 
21 items, 2 – 3 
minutes to complete. 
Parents’ Psychological 
Distress 
The PHQ-8 and the State-Trait Anxiety 
Inventory will be used to assess depressive 
and anxiety symptoms. These symptoms 
represent the general construct of 
psychological distress. 
8 items on PHQ-8 (5 
minutes) and 40 
items on STAI (10 
minutes) 
Parents’ Sleep Quality 
An abbreviated version of the Pittsburgh 
Sleep quality Index, a validated tool for 
assessing self-reported sleep quantity and 
quality, will be developed for this project.   
10 items, 2 – 3 
minutes to complete.   
Parents’ Hypoglycemic 
Fear 
The Hypoglycemic Fear Survey-Parents 
(HFS-P) is a validated tool to assess parents’ 
anxiety and behavior concerning possible 
hypoglycemia.   
18 items, 5 – 10 
minutes to complete 
Parents’ Hypoglycemic 
Confidence 
A new version of the Hypoglycemic 
Confidence Questionnaire, modified for use 
by parents, will be developed for this project.   
8 items, 2 – 3 
minutes to complete 
Health-related quality of 
life 
Parents will complete the diabetes specific 
version of the Pediatric Quality of Life 
Inventory (PedsQL) to provide a report of 
their perception of the child’s quality of life. 
This cuts across social, emotional, academic, 
and health domains. 
23 items. 5-10 
minutes to complete. 
Satisfaction with 
Glucose Monitoring 
The Glucose Monitoring System Satisfaction 
Survey (GMSS-T1D) is a validated tool used 
to assess treatment satisfaction with glucose 
monitoring devices and its impact on quality 
of life and other patient-reported outcomes. 
15 items. 5-10 
minutes to complete. 

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Use and Comfort with 
Technology 
Objective questions documenting the 
frequency of use and types of technologies 
used. Both general (e.g., smartphone) and 
diabetes-specific (e.g., trend program). 
23 items. 5 minutes 
to complete. 
Demographic and 
Family Data 
Parents will complete a questionnaire on the 
family’s structure, racial and ethnic 
background, indicators of socioeconomic 
status, insurance status (public vs. private), 
and other essential characteristics. 
5 minutes  
Behavioral Outcomes 
Diabetes management 
behaviors 
Amount of time spent in Auto Mode; blood 
glucose monitoring frequency (by meter 
download); adherence to pump boluses;  
Download (no time 
burden for 
participants) 
Health care utilization 
Number of visits and calls to the diabetes 
care team 
Tracking by interview 
(10 minutes to 
complete) 
 
Table 4. Measures obtained from child 
Health Outcomes 
HbA1c measurement  
Participants will provide a small 
fingerstick sample of blood (capillary) 
during their routine clinic visit. This will be 
done using the DCA in clinic or local lab 
method. 
Gold standard 
measure of 
glycemic control 
Glycemic excursion 
measures 
Time in range (70 to 180 mg/dL); percent 
below 70 and 60 mg/dL as indicators of 
hypoglycemia, and above 180 and 250 
mg/dL as indicators of hyperglycemia; 
additional indices of variability including 
standard deviation will also be calculated 
 
 
In addition, parents will be asked to complete a brief online survey (< 10 minutes) at the following intervals 
since randomization – 4, 8, and 12 weeks. These online surveys will consist of the Diabetes Distress Scale (3 
items), PHQ-8 (8 items), and the short form of the STAI (10 items). All surveys can be completed online via 
RedCap.  
 
Schedule 
Stanford IRB approval will be in March, 2017.  Upon entering the extension phase of the toddler 670G study 
subjects will be recruited for this study.  We anticipate this will begin occur between July through August of 
2017.  The study will have a 3 month duration so we anticipate completing the study in September through 
December of 2017.   
 
 
Biostatistics and Data Analysis 

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This is a pilot and feasibility study aimed at determining preliminary efficacy of interventions to optimize 
the use of the 670G hybrid closed-loop in toddlers.  It will allow assessment of the effect of specific 
interventions on improving use of the system and improving glucose control.  In addition, collection of these 
data will allow us to determine personnel demands and timing of interventions worth pursuing in a larger 
clinical trial. Our team has extensive experience in database design and implementation, use of web-based 
assessment, data management, and data analysis. We will utilize the RedCap survey system to format all 
measures in to electronic form for completion online or in-person via computer or iPads. Data collected from 
participants will be housed on the RedCap server, which is encrypted and HIPAA-compliant, with secure 
access for unique study IDs assigned to each participant. RedCap survey data is then ready for download by 
study staff and will be imported to SAS 9.3 for data cleaning and analysis.  
Sample size and power calculations were conducted with consideration of a clinically meaningful 
change in the primary outcome – percent time in target range – and the feasibility of enrolling participants from 
the continuation trial. Each site has the potential to enroll 4 to 8 subjects in the primary study, and we expect 
that 70 to 80% would opt for the continuation phase and to be enrolled in the proposed study.   
The primary effect we are interested in is percent change in the amount of time spent in the target 
glucose range from baseline to study completion. Data from our CGM study with toddlers (NIDDK funded DP3; 
Buckingham PI) show that of the sixteen 2-6 year-olds in the study they achieve, on average, only 45% time in 
70-180 mg/dL target range (standard deviation = 15%). Our hypothesized change will be a 10% improvement 
in time spent in target range. There is sufficient power (0.9) to detect this change in a sample size of 26. 
Another aspect of calculating power in this study is the actual number of participants exposed to the planned 
interventions after a glucose “failure.” Over 90% of the participants in our DP3 toddler study experienced a 
glucose failure of less than 60% time in target range. Further, the table below shows the results of glucose 
failures from the DirectNet cohort of toddlers using CGM (Ped Diabetes 13:301-7, 2012).  
 
Table 1.  Expected Failure Rates 
 
Months 
 
0 
1 
2 
3 
4 
5 
6 
 
 
 
 
 
 
 
 
Glucose Failure (not having at least 
65% of readings in the 70-180 mg/dL 
range) 
- 
70% 
70% 
70% 
70% 
75% 
75% 
 
The SMART design of our proposed study allows for randomization to one of 3 conditions when there is 
a glucose failure (2 interventions and 1 control). Because of this, participants can contribute to more than one 
comparison which increases power. This makes the SMART design very efficient, particularly when examining 
multiple treatment strategies, which is what clinicians do in these cases. Our primary outcome will be Glucose 
Failure, which we expect 80-90% of participants to experience. With 27 participants available for randomization 
after a Glucose Failure and each subject assigned at least once to each of the three intervention groups, there 
is only 73% power to detect a difference of 10% change in time spent in range for a given intervention.   In 
other words, going from 45% time spent in range at baseline to 55% time spent in range at study completion; 
an outcome of 10% change.  Thus, while the percent change in the sample from baseline to the end of the 
continuation phase does appear to be adequately powered for the group, the testing of individual interventions 
is underpowered. We will proceed with caution when estimating likely effect sizes for each intervention based 
on the results of the planned analyses.   
Our primary outcome will be tested in two ways. First, by using latent growth curve models to compare 
change in response to treatment strategies, we can examine outcomes from checkpoint to checkpoint. For 
example, we can test percent change in time spent in range from week 2 to 4 and determine which intervention 
is associated with promotion of change during that time period. Because more than three time points are 
available in this study, nonlinear trajectories will also be examined. Second, we will also examine the treatment 
effect using separate individual trajectory models for the primary outcome across the entire 3 months of the 
study. These analyses will inform more precise sample size considerations based on observed effect sizes for 
a larger efficacy trial conducted after this proposed research is completed. 
 
Study population 

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The patient population is children with type 1 diabetes and their parents who are actively enrolled in the IRB 
and FDA approved Medtronic CEP302 study (IDE# G150247, NCT02660827) . Parents (18 years and older) 
will provide informed consent for their own participation and parental permission for their child to participate. 
We will enroll and randomize 40 families. 
 
Eligibility criteria 
 
To be eligible for the study, a child must meet the following criteria: 
1. Enrollment in the continuation phase of the Medtronic CEP 302 study 
Ages 2 to <7.0 years of age 
 
 
Expected duration of the study participation  
 
Duration of study participation is expected to be three months.  
 
Start Date:  As early as September, 2017. 
 
End Date:  As late as September, 2018  
 
Adverse Event Reporting and Safety Monitoring 
 
Overview of Safety Monitoring 
 
All participants will have glucose data reviewed at planned intervals for study adherence. All of the other 
medical monitoring of these subjects are done as part of the IRB and FDA approved Medtronic CEP302 study 
(IDE# G150247, NCT02660827) 
 
 
Definition of Adverse Event 
 
Adverse event reporting and definitions for these research participants will be defined and carried out via the 
IRB and FDA approved Medtronic CEP302 study (IDE# G150247, NCT02660827), as these encompass all the 
inherent risks of Type 1 Diabetes, insulin pump use, and continuous glucose sensor use.  
 
 
 
 
 
Recording of adverse events 
 
Reportable adverse events and serious adverse events are defined and carried out in accordance with the IRB 
and FDA approved Medtronic CEP302 study (IDE# G150247, NCT02660827 
 
Data and safety monitoring 
 
Data and safety monitoring will be carried out in accordance with the IRB and FDA approved Medtronic 
CEP302 study (IDE# G150247, NCT02660827. There is no additional safety monitoring due to the educational 
intervention described here. 
 
 
 
Potential risks and side effects 
 
Loss of confidentiality is a potential risk, and is protected by the safeguards discussed above.  

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Psychological and human factors testing may make study participants uncomfortable. Subjects are free to 
withdraw from the study at any time. A psychologist or a health care professional will be available to help them 
with their stress or anxieties. 
 
Distress or discomfort experienced by participants as they complete surveys is not considered an adverse 
event. However, we have trained psychologists on staff who will be available to address any distress or 
discomfort and initiate referrals if requested. 
 
Adequacy of protection against risks 
 
Recruitment and informed consent 
 
All minorities will be encouraged to participate. Economically and educationally disadvantaged people, parents 
who are employed at the clinical center (Stanford, the University of Colorado, Indiana University, Yale 
University, and University of South Florida) will be eligible to enroll their child in this study if they meet all the 
study criteria.  
 
Participation will be voluntary and all participants must provide consent prior to inclusion in this research study. 
The primary investigator at each of the participating clinical sites, or one of their designees, will explain the 
nature, purpose, expected duration, and risks of study participation to each eligible family. The primary 
investigator at each site, or one of their designees, will also obtain consent and authorization for the release of 
personal information. 
 
 
Protections against risk 
 
All protocols and consent documents will be approved by the local IRB at each clinical site. 
 
 
 
 
Study stopping criteria 
 
Individual subjects will be removed from the study if they are removed from the CEP302 study 
 
 
 
Miscellaneous Considerations 
 
Benefits 
 
It is expected that this protocol will yield knowledge about the impact of closed-loop insulin pump on families 
with young children with type 1 diabetes. The introduction of a closed-loop system might allay parents’ fears, 
ease their sense of diabetes-related distress and foreboding, and impact glycemic variables, however there is 
no guarantee of any benefit from participating in this research study. 
 
 
Subject compensation 
 
There will be no cost to the subjects to participate in this research study. Parents will receive $50 for each of 
two surveys, completed at the enrollment and final visits. In total, a family can receive $100 for completion of 
the study.  
 
Subject withdrawal 

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Participation in the study is voluntary, and a subject may withdraw at any time. The investigator may withdraw 
a subject who is not complying with the protocol. For subjects who withdraw, their data will be used up until the 
time of withdrawal. 
 
Confidentiality 
 
For security and confidentiality purposes, subjects will be assigned an identifier that will be used instead of 
their name. De-identified subject information may also be provided to research sites involved in the study. 
 
Level of risk 
This research proposal in children is consistent with 21 CFR 50.51 - Clinical investigations involving not 
involving greater than minimal risk 
 
Devices 
 
There are no study devices other than those used in the IRB and FDA approved Medtronic CEP302 study 
(IDE# G150247, NCT02660827)