Fully Automated Closed Loop Control in Adolescents With Type 1 Diabetes (Rocket AP)
Phase: NA
Conditions: Type 1 Diabetes
Sponsor: University of Virginia

 
UVA CENTER FOR DIABETES TECHNOLOGY 
 
 
Fully Automated Closed Loop Control in 
Adolescents with Type 1 Diabetes (RocketAP) 
 
 
 
 
Protocol Chair 
Mark DeBoer, MD  
University of Virginia 
Center for Diabetes Technology 
 
 
Version Number: v1.3 
 17-Nov-2020 
 
 

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KEY ROLES 
 
Protocol Principal Investigator 
 
Name, degree 
Mark DeBoer, MD, MSc., MCR 
Institution Name 
University of Virginia Center for Diabetes Technology  
 
 

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PROTOCOL VERSION HISTORY 
Version 
Number 
Author(s) 
Approver 
Effective Date 
Revision Description 
1.0 
Mark DeBoer  
 
Original Protocol 
1.1 
Jon Olson 
Mary Oliveri 
10-Aug-2020 
FDA Review:  
• 
Added stopping criteria of either 
one attributable DKA event or 
one 
attributable 
severe 
hypoglycemia 
event 
(section 
11.9.1) 
• 
Added Definition of Data Breach 
(section 11.11) 
1.2 
Jon Olson 
Mark DeBoer 
21-Oct-2020 
IRB FB Review: 
• 
Inserted 
Covid-19 
Precautions 
(section 10.3) 
1.3 
Jon Olson 
Mark DeBoer 
11-Nov-2020 
Follow-up Review: 
• 
Expanded on Covid-19 precautions  
 
 

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SITE PRINCIPAL INVESTIGATOR STATEMENT OF COMPLIANCE 
 
Protocol Title: Fully Automated Closed Loop Control in Adolescents with Type 1 Diabetes 
(RocketAP) 
Protocol Version/Date: v1.2/17-Nov-2020 
I have read the protocol specified above.  In my formal capacity as a Site Principal Investigator, 
my duties include ensuring the safety of the study participants enrolled under my supervision.  It 
is understood that all information pertaining to the study will be held strictly confidential and 
that this confidentiality requirement applies to all study staff at this site. 
This trial will be carried out in accordance with ICH E6 Good Clinical Practice (GCP) and as required 
by the following: United States (US) Code of Federal Regulations (CFR) applicable to clinical 
studies (45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812). 
As the Principal Investigator, I will assure that no deviation from, or changes to the protocol 
will take place without prior agreement from the sponsor and documented approval from the 
Institutional Review Board (IRB), or other approved Ethics Committee, except where necessary 
to eliminate an immediate hazard(s) to the trial participants. 
All key personnel (all individuals responsible for the design and conduct of this trial) have 
completed Human Participants Protection Training and Good Clinical Practice Training.  Further, 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments. 
 
Investigator’s Signature __________________________________Date: _____ / _____ / _____ 
Investigator’s Name: ________________________________ 
Site Name:  University of Virginia 
 
 

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LIST OF ABBREVIATIONS 
ABBREVIATION 
DEFINITION 
ADRR 
Average Daily Risk Range 
AP 
Artificial Pancreas 
BG 
Blood Glucose 
BT/BTLE 
Bluetooth, Bluetooth low energy 
CGM 
Continuous Glucose Monitoring 
CLC 
Closed-Loop Control 
CiQ 
Tandem t:slim X2 Insulin Pump with Control-IQ Technology 
CSII 
Continuous Subcutaneous Insulin Injection 
DKA 
Diabetic Ketoacidosis 
DSMB 
Data Safety Monitoring Board 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HbA1c 
Hemoglobin A1c 
HBGI 
High Blood Glucose Index  
IDE 
Investigational Device Exemption 
IOB 
Insulin-on-Board 
LBGI 
Low Blood Glucose Index  
POC 
Point-of-Care 
QC 
Quality Control 
rMPC 
Regular Model Predictive Control 
UI 
User Interface 
 
 

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PROTOCOL SUMMARY 
PARTICIPANT AREA 
DESCRIPTION 
Title 
Fully Automated Closed Loop Control in Adolescents with Type 1 Diabetes (RocketAP) 
Investigational Device 
Reactive Open-loop and Carbohydrate Kinetics EsTimation (Rocket) based Fully Automated 
Artificial Pancreas 
Objectives 
The purpose of this study is to show the safety and feasibility of a fully new fully automated 
AP controller based on automated meal priming and CHO kinetics estimation, within the 
UVA AP modular architecture. 
Study Design 
A randomized cross-over trial assessing glycemic responses to two different approaches to 
insulin dosing for carbohydrate ingestion (announced vs. unannounced), with two different 
AP systems (RocketAP vs. USS Virginia, aka Control-IQ, in random order)  
Number of Sites 
One 
Endpoint 
The primary outcome will be time in range 70-180 mg/dL from dinner time until midnight. 
Population 
Key Inclusion Criteria 
• Age 12-25 
• Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one 
year  
• Currently using insulin for at least six months 
• Currently using insulin pump for at least three months  
Key Exclusion Criteria  
• Hemoglobin A1c < 12% 
Sample Size  
• Pilot Study: complete up to 3 participants  
• Main Study: complete up to 20 participants 
Treatment Groups 
• RocketAP 
• USS Virginia, aka Control-IQ  
Participant Duration 
Pilot Study:  Participants will be admitted to a local hotel for approximately 42 hours and will 
have an experimental dinner with the RocketAP with no-carbohydrate announcement.   
Main Study: Participants will be admitted to a local hotel for approximately 64 hours.  
Protocol Overview/Synopsis 
Participants will be randomized to either the RocketAP experimental group or the Control-IQ 
control group. Each group will participate in two (2) ~64 hour admissions. During one 
admission, the RocketAP (Meal Control Module) group will have one dinner session with a 
normal carbohydrate announcement and one dinner session with no carbohydrate 
announcement.  During the alternate admission, the participate will have the will have one 
dinner session with a normal carbohydrate announcement and one dinner session with no 
carbohydrate announcement while using the Control-IQ equipment.  These studies will be 
performed under precautionary conditions where we will attempt to create a COVID-free 
“bubble” where participants and study personnel will have two rounds of testing to ensure 
that those in the “bubble” have very low risk of infection. 

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STUDY VISITS AND PROCEDURES SCHEDULE  
 
Screening 
Study 
Equipment 
Training 
CGM Run-In 
Phase 
 Pre-
Admission 
Check-In  
Study 
Admission 
#1 
Post-
Admission 
Check-In 
Pre-
Admission 
Check-In 
Study 
Admission 
#2 
Post-
Admission 
Check-In 
Location 
Clinic/   
Remote 
 Clinic/   
Remote 
Clinic/ 
Remote 
Home 
Phone/ 
Email/Text 
  
Hotel 
Phone/ 
Email/Text  
Phone/ 
Email/Text 
  
Hotel 
Phone/ 
Email/Text  
Visit 
1 
2 
x 
3 
4 
5 
6 
7 
8 
Hotel Day  
NA 
NA 
x 
NA 
1-4 
NA 
NA 
5-8 
NA 
Informed 
Consent 
X 
 
 
 
 
 
 
 
 
Eligibility 
Assessment 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
HbA1c  
X 
 
 
 
 
 
 
 
 
Pregnancy test 
(if applicable) 
X 
X 
 
 
X 
 
 
X 
 
Physical Exam 
X 
 
 
 
 
 
 
 
 
Vital Signs 
(height/weight) 
X 
 
 
 
 
 
 
 
 
Randomization 
 
 
 
 
X 
 
 
 
 
COVID Testing 
 
 
 
X 
X 
 
 
X 
 
CGM Run-In 
(non-G6 users) 
 
 
~14 days if 
needed 
 
 
 
 
 
 
Study Dinner 
Sessions 
 
 
 
 
Day 2 & 3 
 
 
Day 6 & 7 
 
Survey / 
Questionnaires  
 
X 
 
 
Post  
 
 
Post  
X 
Review diabetes 
management 
and AEs 
 
 
 
 
X 
 
X 
 
X 
X 

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Table of Contents 
1 
Chapter 1 Background ......................................................................................................... 13 
2 
1.1 Introduction ........................................................................................................................ 13 
3 
1.2 Study Objective ................................................................................................................... 13 
4 
1.3 Study Design........................................................................................................................ 14 
5 
1.4 Study Device Download ...................................................................................................... 17 
6 
1.5 Study System Issues ............................................................................................................ 17 
7 
1.6 Purpose/Objectives of Clinical Study .................................................................................. 17 
8 
Chapter 2 Study Devices ...................................................................................................... 18 
9 
2.1 Insulin Pump ....................................................................................................................... 18 
10 
2.2 Continuous Glucose Monitor .............................................................................................. 18 
11 
2.3 Blood Glucose Meter and Strips ......................................................................................... 18 
12 
2.4 Ketone Meter and Strips ..................................................................................................... 18 
13 
2.5 Study Devices Accountability Procedures........................................................................... 18 
14 
Chapter 3 Study Screening ................................................................................................... 19 
15 
3.1 Participant Recruitment and Enrollment ............................................................................ 19 
16 
3.2 Informed Consent and Authorization Procedures .............................................................. 19 
17 
3.3 Screening Procedures ......................................................................................................... 19 
18 
3.4 Participant Inclusion Criteria............................................................................................... 19 
19 
3.5 Participant Exclusion Criteria .............................................................................................. 20 
20 
3.6 Eligibility Screening Procedures  ......................................................................................... 21 
21 
3.7 Demographic Data Survey .................................................................................................. 22 
22 
Chapter 4 Randomization .................................................................................................... 23 
23 
4.1 Pilot Study Participants ....................................................................................................... 23 
24 
4.2 Main Study Participants ...................................................................................................... 23 
25 
Chapter 5 Study Equipment Training .................................................................................... 24 
26 
5.1 CGM Training ...................................................................................................................... 24 
27 

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5.2 Activity Tracker ................................................................................................................... 25 
28 
5.3 Study Insulin Pump ............................................................................................................. 25 
29 
Chapter 6 Pilot Study ........................................................................................................... 27 
30 
6.1 Run-In Phase ....................................................................................................................... 27 
31 
6.2 Qualifications and Role of the Staff .................................................................................... 27 
32 
6.3 Pre-Admission Check-In Visit .............................................................................................. 27 
33 
6.4 Admission Check-In ............................................................................................................. 28 
34 
6.5 Hotel Admission Glycemic Treatment Guidelines .............................................................. 28 
35 
6.6 Study Meals ......................................................................................................................... 29 
36 
6.7 Admission Activities ............................................................................................................ 29 
37 
6.8 Admission Discharge ........................................................................................................... 29 
38 
6.9 Post Admission Check-In Visit ............................................................................................. 29 
39 
6.10 Medical Monitor Review ................................................................................................... 30 
40 
Chapter 7 Main Study .......................................................................................................... 31 
41 
7.1 Run-In Phase ....................................................................................................................... 31 
42 
7.2 Qualifications and Role of the Staff .................................................................................... 31 
43 
7.3 Pre-Admission Check-In Visit .............................................................................................. 31 
44 
7.4 Admission Check-In ............................................................................................................. 32 
45 
7.5 Hotel Admission Glycemic Treatment Guidelines .............................................................. 32 
46 
7.6 Study Meals ......................................................................................................................... 33 
47 
7.7 Admission Activities ............................................................................................................ 33 
48 
7.8 Admission Discharge ........................................................................................................... 34 
49 
7.9 Post Admission Questionnaire ............................................................................................ 34 
50 
7.10 Post Admission Check-In Visit ........................................................................................... 34 
51 
7.11 Medical Monitor Review ................................................................................................... 34 
52 
Chapter 8 Medical Monitor Review ...................................................................................... 35 
53 
8.1 Medical Monitor Study Safety Data Review ....................................................................... 35 
54 

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8.2 Medical Monitor Decisions ................................................................................................. 35 
55 
8.3 Medical Monitor Main Study Safety Data Review .............................................................. 35 
56 
Chapter 9 Testing Procedures .............................................................................................. 36 
57 
9.1 Laboratory / Point of Care Testing ...................................................................................... 36 
58 
9.2 Questionnaire Schedule ...................................................................................................... 36 
59 
Chapter 10 Risks Associated with Clinical Trial ..................................................................... 37 
60 
10.1 Potential Risks and Benefits of the Investigational Device ............................................... 37 
61 
10.2 General Considerations..................................................................................................... 41 
62 
10.3 COVID 19 Risk Mitigation Plan and Justification ............................................................... 41 
63 
Chapter 11 Adverse Events, Device Issues, and Stopping Rules ............................................. 45 
64 
11.1 Definitions ......................................................................................................................... 45 
65 
11.2 Reportable Events ............................................................................................................. 46 
66 
11.3 Relationship of Adverse Event to Study Device ................................................................ 47 
67 
11.4 COVID Transmission .......................................................................................................... 48 
68 
11.5 Intensity of Adverse Event ................................................................................................ 48 
69 
11.6 Coding of Adverse Events ................................................................................................. 49 
70 
11.7 Outcome of Adverse Events ............................................................................................. 49 
71 
11.8 Reportable Device Issues .................................................................................................. 50 
72 
11.9 Timing of Event Reporting ................................................................................................ 51 
73 
11.10 Stopping Criteria ............................................................................................................. 51 
74 
11.11 Independent Safety Oversight ........................................................................................ 52 
75 
11.12 Definition of a Data Breach ............................................................................................. 52 
76 
Chapter 12 Miscellaneous Considerations ............................................................................ 53 
77 
12.1 Prohibited Medications, Treatments, and Procedures .................................................... 53 
78 
12.2 Participant Withdrawal ..................................................................................................... 53 
79 
12.3 Confidentiality ................................................................................................................... 53 
80 
Chapter 13 Statistical Consideration .................................................................................... 54 
81 

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13.1 Design and Randomization ............................................................................................... 54 
82 
13.2 Sample Size ....................................................................................................................... 54 
83 
13.3 Outcome Measures ........................................................................................................... 54 
84 
13.4 Safety Analyses ................................................................................................................. 55 
85 
13.5 Baseline Descriptive Statistics ........................................................................................... 56 
86 
13.6 Device Issues ..................................................................................................................... 56 
87 
Chapter 14 Data Collection and Monitoring ......................................................................... 58 
88 
14.1 Case Report Forms and Device Data ................................................................................. 58 
89 
14.2 Study Records Retention .................................................................................................. 58 
90 
14.3 Protocol Deviations ........................................................................................................... 58 
91 
Chapter 15 Ethics/Protection of Human Participants ............................................................ 59 
92 
15.1 Ethics Standard ................................................................................................................. 59 
93 
15.2 Institutional Review Boards .............................................................................................. 59 
94 
15.3 Informed Consent Process ................................................................................................ 59 
95 
Chapter 16 References ......................................................................................................... 61 
96 
 
 
97 

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Chapter 1  Background 
98 
 
99 
Maintaining blood glucose (BG) control among adolescents with Type 1 diabetes (T1D) is arguably 
100 
the greatest challenge in entire field of T1D.  While the reasons for this poor control are varied, 
101 
a significant issue relates to missed meal boluses, which affects 65% of adolescents at least once 
102 
weekly,1 with 38% missing at least 15% of their boluses.2 Adolescents who miss four boluses 
103 
weekly experience an increase of 1% in their HbA1c.1  While the advent of the artificial pancreas 
104 
(AP) in this age range offers promise of safe reductions in HbA1c,3 we previously found that the 
105 
AP only partly compensates for missed prandial insulin4—demonstrating that some form of meal 
106 
announcement is necessary for good BG control, even with an AP.  One way to automate this 
107 
process is by sharing the prandial dosing responsibilities between an automated insulin priming 
108 
(based on CGM condition predictive of a safe situation for such insulin dosing) and a closed loop 
109 
controller capable of reconstructing (estimating) the prevailing glucose rate of appearance from 
110 
an unannounced meal. We have developed such an insulin priming schema and integrated it into 
111 
a new version of the robust Model Predictive Controller UVa AP system (called the RocketAP).     
112 
In the current study, we are testing this new AP system in two configurations: hybrid and fully 
113 
automated, among up to 20 adolescents. Our primary outcome will be one of efficacy in assessing 
114 
how well the new system controls post-prandial blood sugar in the absence of carbohydrate 
115 
announcement as compared to the same situation but using the Control-IQ closed loop 
116 
algorithm, also designed at UVa and using the same modular architecture and safety system, but 
117 
without insulin priming and with a less advanced model-based controller.  Further comparisons 
118 
will be made to blood sugar control on RocketAP with carbohydrate announcement and on 
119 
Control-IQ with carbohydrate announcement.  Adolescents will be started on the respective UVa 
120 
artificial pancreas systems (RocketAP and Control-IQ in random order, both implemented on the 
121 
DiAs platform, MAF 2109) and followed over the course of two dinners on each of the two 
122 
platforms: a dinner where carbohydrate is announced as normal and the second where no 
123 
announcement is made.    
124 
We hypothesize that performances of RocketAP in fully automated mode will lie in between 
125 
Hybrid and Fully Automated Control-IQ. In time, this may provide an opportunity to improve 
126 
blood sugar control among adolescents who miss meal announcement. 
127 
 
128 
The purpose of this study is to test the RocketAP closed loop algorithm, a new algorithm 
129 
leveraging the UVA modular architecture to insert a new basal rate modulator and a new insulin 
130 
priming schema inside our validated framework including the UVA safety system module. We will 
131 

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enroll up to 20 adolescents in a randomized cross-over trial, comparing blood glucose time in 
132 
range 70-180 mg/dL following dinners consumed with or without announcement contrasting our 
133 
currently approved algorithm (Control-IQ) with this new version.  
134 
 
135 
We will recruit approximately 30 participants, age 12-25 years, with a goal to have up to 20 
136 
participants complete the trial. The study will be performed overnight at a local hotel near the 
137 
University Medical Center.   This will be done under conditions where we will attempt to create 
138 
a COVID-free “bubble,” further described in section 10.3.    The pilot study, which will have 
139 
between 1 and 3 participants and be up to 2 days will be in a hotel/rented house. (Use of a rented 
140 
house for a small group allows for more control over contact with non-study individuals.)  
141 
Additional COVID-19 precautions are described below still apply. 
142 
 Recruitment and Screening 
143 
Participants will be recruited from the UVa Center for Diabetes Technology registry, social media 
144 
advertisements, physician contacts at pediatric diabetes clinics in Virginia (UVa, Virginia 
145 
Commonwealth University, Children’s Hospital of the King’s Daughters) and camp attendance 
146 
data.  Potential participants will be informed of the study and offered a chance to have answered 
147 
questions.  Participants, and a parent if <18 years old, will provide written informed consent and, 
148 
if participant is <18 years old, assent will also be obtained.  Participants will be screened at a visit 
149 
before the beginning of hotel stay to confirm eligibility.  The screening visit can be performed by 
150 
video conferencing.  Prior to participation in the hotel study, participants will agree to self-isolate 
151 
and have COVID testing. 
152 
 CGM Data Collection 
153 
Following enrollment participants will be trained in use of the Dexcom G6 system, provided with 
154 
adequate study supplies and have a Dexcom sensor placed.  This training can also be done via 
155 
video conferencing, with supplies sent to the family.  This study visit will be followed by 2 weeks 
156 
of CGM and pump data collection at the participant’s home/usual routine.  Participants who have 
157 
previously used a Dexcom CGM and have glucose data for the 2 weeks prior to the screening visit 
158 
can skip the 2-week data collection.   Participants will then be randomized to be on one artificial 
159 
pancreas system or the other 1st (RocketAP or Control-IQ).  This will be performed using two 
160 
permuted blocks of 4 and one permuted block of 2. 
161 
 Study Hardware/Software 
162 
The study itself will involve use of the DiAs prototyping platform (MAF 2109), connected to a 
163 
Tandem t:ap research pump and a Dexcom G6 sensor, and implementing either RocketAP or 
164 
Control-IQ (in random order).  Upon arrival at the  hotel, participants will be instructed in how to 
165 

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use the Tandem research pump as well as the UVa AP systems, including stopping the system 
166 
and bolusing for food.  
167 
 Timing of UVa Artificial Pancreas Use 
168 
Upon arrival to  hotel, participants will be connected to a Tandem research pump connected to 
169 
the UVa DiAs platform and their Dexcom G6 Transmitter will be linked with DiAs. Participants will 
170 
then be taught how to use DiAs in this configuration. The research pump will be programmed 
171 
with the adolescent’s usual insulin parameters.     
172 
Participants will have their blood sugar managed through this system during the entirety of the 
173 
time at  hotel.   
174 
 Study Dinner Sessions 
175 
Study dinners and timing: On four separate days (hotel days 2, 3, 6 and 7), participants will be 
176 
followed for the experimental dinners as part of the Study Dinner Sessions to compare blood 
177 
glucose control using four different approaches to insulin management for carbohydrate control 
178 
(Figure 1).  These Study Dinner Sessions start approximately 3-4 hours before the dinner and 
179 
continue for approximately 12 hours after the dinner.  During the Study Dinner Sessions, 
180 
participants will consume structured dinners (with identical protein, fat, and carbohydrate 
181 
content between the Study Dinner Sessions) while on the two UVa AP closed loop algorithms 
182 
(RocketAP or Control-IQ—in random order); for each, insulin dosing on the first Study Dinner 
183 
Session will be via normal carbohydrate announcement and the DiAs CGM-based bolus 
184 
calculator, and on the second Study Dinner Session with no carbohydrate announcement (In the 
185 
case of the RocketAP artificial pancreas system, the insulin priming will be in place to detect and 
186 
dose for unannounced carbohydrate.)  For other meals on the artificial pancreas system during 
187 
the  hotel stay, normal carbohydrate announcement will be performed.  
188 

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189 
Figure 1:  Timeline of the Study Dinner Sessions 
190 
The order of the AP system tested (RocketAP vs. Control-IQ) is determined randomly.  The order 
191 
of carbohydrate (CHO) announcement will be the same in both cases.  Study Dinner Sessions will 
192 
likely be performed during two  hotel admissions separated by no more than 8 weeks. 
193 
Blood glucose levels will be followed via continuous glucose monitor, and the primary outcome 
194 
will be percent time in blood glucose range 70-180 mg/dL during the 6 hours following start of 
195 
the meal. Study staff who will be present will include nursing staff and technical staff; a study 
196 
physician will be available either on-site or nearby off-site at all times. Hyperglycemia and 
197 
hypoglycemia treatment protocols will be followed per CDT protocol. We anticipate more 
198 
significant cases of hyperglycemia during dinners managed without carbohydrate 
199 
announcement; participants will be encouraged to drink large amounts of non-caloric beverages, 
200 
particularly after these meals.    
201 
The UVa AP systems will be initiated upon arrival to the hotel the afternoon/evening before the 
202 
first of the Study Dinner Sessions. UVa CDT study staff will monitor CGM output continuously and 
203 
manage blood sugar control issues.  At the end of the second Study Dinner Session, the 
204 
participant will be placed on home insulin management (or adjustment based on diabetes camp 
205 
management).  
206 
Stopping criteria for and individual study dinner session:  A Study Dinner Session will be stopped 
207 
for an individual participant for any of the following: 
208 
• Ketones >1.5 mmol 
209 
• Known site failure  
210 

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• Two separate hypoglycemia events where the blood glucose falls below 50 mg/dL 
211 
• The behavior of the participant is such that there is concern about his/her ability to 
212 
continue to adhere to the protocol 
213 
• At the discretion of the study physician. 
214 
 
215 
Before discharge from the hotel, all study devices will be turned in to study staff for device 
216 
download and the participants will be placed on usual diabetes management. 
217 
 
218 
If the CGM signal becomes unavailable for more than 20 minutes consecutively, closed loop will 
219 
not operate to automatically adjust insulin.  If the CGM is not connected, the system will revert 
220 
to usual function of the pump and deliver insulin with the insulin dosing parameters programmed 
221 
in the system for that individual. Resumption of closed-Loop will occur automatically once CGM 
222 
signal is available again. 
223 
If the study system is unable to maintain pump connectivity, the pump will automatically revert 
224 
to pre-programmed basal insulin delivery after 30minutes without any need for instruction from 
225 
the user. 
226 
 
227 
 Study Participants 
228 
Enrollment in the Pilot Study will proceed with the goal of completing 3 participants. Up to 6 
229 
participants may sign the consent/assent forms.   
230 
Enrollment in the Main Study will proceed with the goal of completing approximately 20 
231 
participants.  Up to 30 participants may sign the Main Study consent/assent forms.  
232 
 Clinical Sites 
233 
The study will be performed at the University of Virginia, with screening procedures taking place 
234 
at the Clinical Research Unit or at a local hotel/rental house.  
 
235 

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Chapter 2 Study Devices 
236 
 
237 
The study systems will utilize the Tandem t:ap research pump connected to the UVa DiAs system 
238 
run on a dedicated external smart phone, running either the RocketAP control algorithm or the 
239 
Control-IQ control algorithm (in random order).   
240 
 
241 
The study CGM will include Dexcom G6 transmitter and sensors. The CGM sensor is viable for 10 
242 
days. 
243 
 
244 
Blood glucose levels will be measured using the Accu-Chek Guide blood glucose meter 
245 
(glucometer). The CGM device will be calibrated, if needed, using the study glucometer and strips 
246 
in accordance with the manufacturer’s labeling.  
247 
 
248 
Blood ketone levels will be measured using the Abbott Precision Xtra meters and strips in 
249 
accordance with the manufacturer’s labeling. The blood glucose meter component of the 
250 
Precision Xtra Device will not be used.  The ketone meter will be available for staff use during the 
251 
study admissions. 
252 
 
253 
Device serial numbers will be recorded and use of equipment will be tracked. 
 
254 

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Chapter 3 Study Screening  
255 
 
256 
Pilot Study:  Enrollment goal in the Pilot Study will be to complete 1 participant. Up to 4 
257 
participants may sign consent/assent forms.  
258 
Main Study:  Enrollment in the study will proceed with the goal of completing up to 20 
259 
participants.  Participants will initially be randomized for the order of their 3 experimental meals 
260 
use during the study.  Up to 30 participants may sign the consent/assent forms. 
261 
 
262 
Before consent has been obtained, participants will be asked inclusion/exclusion criteria 
263 
questions during pre-screening to determine study eligibility. Before completing any procedures 
264 
or collecting any data that are not part of usual care, written informed consent (and assent, when 
265 
applicable) will be obtained. Potential eligibility may be assessed as part of a routine-care 
266 
examination.   
267 
A participant is considered enrolled when the informed consent form has been signed by the 
268 
participant and the study team. 
269 
Consenting procedures and documentation is defined in section 15.3.  
270 
 
271 
After informed consent has been signed, a potential participant will be evaluated for study 
272 
eligibility through the elicitation of a medical history, performance of a physical examination 
273 
by licensed personnel, and pregnancy testing (if applicable) to screen for exclusionary medical 
274 
conditions.  A physical exam documented in the prior year can suffice for the physical exam. 
275 
Individuals who do not initially meet study eligibility requirements may be rescreened at a later 
276 
date per investigator discretion. 
277 
 
278 
The participants must meet all of the following inclusion criteria in order to be eligible to 
279 
participate in the study. 
280 
1. Age ≥12.0 and ≤25 years old at time of consent 
281 
2. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year  
282 
3. Currently using insulin for at least six months 
283 
4. Currently using insulin pump for at least three months  
284 

CLINICAL PROTOCOL 
 
 
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5. Using insulin parameters such as carbohydrate ratio and correction factors consistently on 
285 
their pump in order to dose insulin for meals or corrections  
286 
6. Access to internet and willingness to upload data during the study as needed  
287 
7. For females, not currently known to be pregnant or breastfeeding 
288 
8. If female and sexually active, must agree to use a form of contraception to prevent pregnancy 
289 
while a participant in the study.  A negative serum or urine pregnancy test will be required 
290 
for all females of childbearing potential. Participants who become pregnant will be 
291 
discontinued from the study. Also, participants who during the study develop and express 
292 
the intention to become pregnant within the timespan of the study will be discontinued. 
293 
9. Willingness to suspend use of any personal CGM for the duration of the clinical trial once the 
294 
study CGM is in use 
295 
10. Willingness to use the UVa artificial pancreas system throughout study sessions. 
296 
11. Willingness to switch to lispro (Humalog) or aspart (Novolog) if not using already, and to use 
297 
no other insulin besides lispro (Humalog) or aspart (Novolog) during the study 
298 
12. Total daily insulin dose (TDD) at least 10 U/day and not more than 100 U/d 
299 
13. Willingness not to start any new non-insulin glucose-lowering agent during the course of the 
300 
trial (including metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, biguanides, 
301 
sulfonylureas and naturaceuticals) 
302 
14. Willingness to eat at least 1 g/kg of carbohydrate per day during the hotel (or rental house, 
303 
in the case of the pilot) admission 
304 
15. Willingness to reschedule Study Dinner Sessions if placed on oral steroids 
305 
16. An understanding and willingness to follow the protocol and signed informed consent  
306 
17. Willingness to commit to self-quarantine for at least 5 days before COVID testing. The COVID 
307 
testing will occur 2-3 days before the hotel study.  Also, a willingness to comply with COVID 
308 
precautions as outlined in section 10.3. The COVID test must be negative. 
309 
 
310 
The participant must not have any exclusion criteria in order to be eligible to participate in the 
311 
study.  
312 
1. History of diabetic ketoacidosis (DKA) in the 12 months prior to enrollment 
313 
2. Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to 
314 
enrollment 
315 
3. Pregnancy or intent to become pregnant during the trial 
316 
4. Currently being treated for a seizure disorder 
317 

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5. Planned surgery during study duration  
318 
6. Treatment with any non-insulin glucose-lowering agent (including metformin, GLP-1 agonists, 
319 
pramlintide, 
DPP-4 
inhibitors, 
SGLT-2 
inhibitors, 
biguanides, 
sulfonylureas 
and 
320 
naturaceuticals)  
321 
7. A known medical condition that in the judgment of the investigator might interfere with the 
322 
completion of the protocol. 
323 
8. Use of an automated insulin delivery mechanism that is not downloadable by the subject or 
324 
study team 
325 
9. Known contact with a COVID-positive individual within 14 days of the hotel/rented house 
326 
studies. 
327 
10. A positive COVID Test within 14 days of study participation, or during study participation. 
328 
 
329 
The participant will be evaluated for study inclusion and exclusion eligibility after the informed 
330 
consent form has been signed by the participant and the study team.  
331 
Individuals who do not initially meet study eligibility requirements may be rescreened at a later 
332 
date per investigator discretion. 
333 
1. Demographics 
334 
o Date of birth 
335 
o Gender  
336 
o Race 
337 
o Ethnicity 
338 
2. Medical History  
339 
o Duration of disease (number of years) 
340 
o Current insulin pump model 
341 
o History of CGM use 
342 
o Current treatment 
343 
i. 
Basal rates 
344 
ii. 
Carbohydrate ratios 
345 
iii. 
Insulin sensitivity factors 
346 
iv. 
Target glucose 
347 
v. 
Average daily insulin 
348 
o History of diabetic ketoacidosis 
349 
o History of severe hypoglycemia  
350 
o History of seizures  
351 

CLINICAL PROTOCOL 
 
 
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o Loss of consciousness 
352 
3. Surgical history 
353 
4. Allergies 
354 
5. Concomitant medications 
355 
6. Physical Examination – A historical history and physical report within 52 weeks of 
356 
screening appointments may be used 
357 
o Weight 
358 
o Height 
359 
o Blood pressure 
360 
o Temperature 
361 
o Heart Rate 
362 
7. Screening Labs 
363 
o Hemoglobin A1c point of care  
364 
o Urine or serum pregnancy test for all women of childbearing potential 
365 
Screening procedures will last approximately 1-2 hours. Screening can be performed via video 
366 
conference.  Once all results of the screening evaluations are available, a decision will be made 
367 
to determine the participant’s eligibility for the study or if one or more part of the screening will 
368 
have to be repeated. If at the first screening or repeat screening an exclusionary condition is 
369 
identified, the participant will be excluded from participation with follow up and referred to their 
370 
primary care physician as needed. The study physician may elect to rescreen participants if their 
371 
clinical situation changes. Notably, screening is for determining study eligibility.  Once 
372 
participants are found to be eligible, they can begin their self-quarantine and COVID testing as 
373 
outlined above. 
374 
 
375 
The Demographic Data Survey will be electronically administered once eligibility has been met.  
376 

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Chapter 4 Randomization  
377 
Participants will receive the three different experimental meals in random order as described 
378 
below. 
379 
 
380 
Pilot participants will not be randomized but will only undergo both a normal carbohydrate 
381 
announcement and an experimental dinner with the RocketAP with no-carbohydrate 
382 
announcement. 
383 
 
384 
Once eligibility is met, the participant may continue to randomization following arrival to the first  
385 
hotel visit. Screening failures and study dropout participants may be replaced. Randomization 
386 
will determine the order of the Study Dinner Sessions, with potential order as shown in Table 1. 
387 
 
Study Dinner Sessions #1 & 2 
 (Hotel days 2 and 3) 
Study Dinner Sessions #3 & 4 
 (Hotel days 5 and 6) 
1. 
RocketAP 
Control-IQ 
 
Study Dinner Session 
#1:   
Normal CHO 
announcement  
Study Dinner Session 
#2:   
No announced CHO 
(insulin priming and 
automated AP 
correction boluses)  
Study Dinner Session 
#3:   
Normal CHO 
announcement  
Study Dinner Session 
#4:   
No announced CHO 
(automated AP 
correction boluses)  
2. 
Control-IQ 
RocketAP 
 
Study Dinner Session 
#1:   
Normal CHO 
announcement  
Study Dinner Session 
#2:   
No announced CHO 
(automated AP 
correction boluses) 
Study Dinner Session 
#3:   
Normal CHO 
announcement  
Study Dinner Session 
#4:   
No announced CHO 
(insulin priming and 
automated AP 
correction boluses) 
Table 1: Randomization Table  
388 
Randomization will occur via selection from the above list using permuted blocks in groups of 4, 
389 
4 and 2.   
 
390 

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Chapter 5 Study Equipment Training 
391 
Equipment training may begin at arrival to  hotel after UVa AP system has been put in place.  The 
392 
purpose of this training is to introduce the study insulin pump and study CGM to the participant.  
393 
The participant’s insulin parameters will be programmed into their study insulin pump by two 
394 
research staff. Subjects will then switch to the study insulin pump. The participant’s personal 
395 
pump and infusion site will be removed. 
396 
The participant will have the insulin pump and sensor on them at all times. Study supplied phones 
397 
will be used if DiAs is the system utilized and otherwise upon participant request.  
398 
 
399 
A study CGM will be provided to all participants at the training session. The participants will be 
400 
provided with CGM equipment and instructed to use the study CGM on a daily basis. If the 
401 
participant has prior use of the CGM, re-training will be specific to the individual. The study team 
402 
may elect to have less frequent CGM users watch the Dexcom online training videos 
403 
(https://www.dexcom.com/training-videos) to assist in the training session.  Study staff training 
404 
may include review of study CGM in real-time to make management decisions and how to review 
405 
the data after an upload for retrospective review. Study staff will specifically identify how alarms 
406 
are set using the app and the frequency that these alarms will repeat. 
407 
The participants personal CGM will be discontinued. The participants will be observed placing the 
408 
sensor and will learn/review how to access the CGM trace via the DiAs phone or the Tandem 
409 
research pump, as needed. The participants will be asked to perform fingerstick blood glucose 
410 
measurements (if needed) in accordance with the labeling of the study CGM device.  
411 
An electronic copy of the CGM user’s guide will be provided for the participants to read. The 
412 
study team will be sure that the participants will leave the training session knowing how to use 
413 
proper use the CGM. The study team will be available for any questions. 
414 
Participants will have the option of using their personal smartphone or receive a study 
415 
smartphone to use in order to collect the data from the devices. If the participant elects to use a 
416 
personal device, the Dexcom app will be downloaded to their phone in order to monitor the 
417 
participant’s CGM values and alerts in real-time may be used. 
418 

CLINICAL PROTOCOL 
 
 
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419 
All participants may be asked to wear an activity tracker (e.g. Fitbit) during the entire study (home 
420 
and hotel admissions) to record information about movement and heart rate though not an 
421 
endpoint in this study. 
422 
 
423 
The study team will be responsible monitoring and managing the study insulin pump during the 
424 
hotel admissions. The participants may be provided a quick overview on its functionality if they 
425 
understand the equipment. 
426 
 Study Insulin Pump Topics  
427 
• The study team will assist the participant in study pump infusion site initiation and will 
428 
start the participant on the study pump. The study pump will be programmed with the 
429 
participant’s usual basal rates and pump parameters. The participant’s personal pump 
430 
will be removed. 
431 
• The participant will be instructed infusion site initiation, cartridge/priming procedures, 
432 
setting up the pump, charging the pump, navigation through menus, bolus procedures 
433 
including stopping a bolus, etc. 
434 
 Other Issues  
435 
The participant will be instructed to notify study staff if they experience any issues with the study 
436 
devices during the hotel admission. Staff will be present in the event that if insulin is delivered 
437 
by any means other than the study pump (e.g. injection of subcutaneous insulin via syringe in the 
438 
event of infusion site failure). If insulin is delivered by any means other than the study pump, the 
439 
study team will be instructed to turn off closed-loop mode for approximately four hours. 
440 
The participant will be asked to alert the study clinical staff during periods of illness that develops 
441 
during use of the AP system (elevated temperature >101.5 degrees Fahrenheit [38.6 degrees 
442 
Celsius], periods of significant illness, or during periods of use of medications such as epinephrine 
443 
for the emergency treatment of a severe allergic reaction or asthma attack in addition to use of 
444 
oral or injectable glucocorticoids to determine if closed-loop use should be temporarily 
445 
discontinued. 
446 
The participant will also be asked to alert the study clinical staff for technical issues with the 
447 
Tandem research pump and/or the DiAs system, including use of the study pump and study CGM 
448 
(open loop mode) during periods of component disconnections or technical difficulties.  Study 
449 
staff contact information will be provided to the participant.  
450 

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A glucagon emergency kit will be available. Participants who currently do not have one will be 
451 
given a prescription for the glucagon emergency kit.  
452 
Glycemic Treatment Guidelines will be available for staff use during the study admissions. 
453 
 Optimization of Insulin Pump Settings 
454 
Data-driven optimization of pump settings can occur any time during the study, particularly if the 
455 
participant contacts the study physician due to concerns about their pump settings due to 
456 
recurring hypo- or hyperglycemia. 
 
457 

CLINICAL PROTOCOL 
 
 
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Chapter 6  Pilot Study  
458 
In order to optimize the flow of the study visits during the Main Study, we will perform a Pilot 
459 
Study at a local hotel. The duration of the hotel admission will be up to 48 hours with the intent 
460 
of collecting appropriate safety data that will be presented to the study Medical Monitor for 
461 
review.  Pilot study participants are eligible to enroll in the Main Study.  
462 
 
463 
Participants not familiar with the CGM will wear the CGM at home for approximately 14 days. 
464 
Other participants who are familiar with the CGM will immediately proceed to the hotel/rented 
465 
house admission. If currently using a Dexcom G6, up to 30 days of data may be obtained from 
466 
the participant’s personal CGM.  
467 
 
468 
For the pilot study, there will be at least two study staff present at all times at the study site, at 
469 
least one of whom will be clinical staff (e.g. nurse, physician, nurse practitioner). There will be a 
470 
physician available either on-site or off-site within a 20-minute drive at all times.  All study staff 
471 
will have received COVID testing within 72 hours of the start of the pilot study.  In addition, one 
472 
of the study medical physicians and one senior engineer will be on call during the entire 
473 
admission. Glucagon for the emergency treatment of hypoglycemia will be available on-site. 
474 
 
475 
Pilot participants will be contacted by the study team approximately 24-48 hours prior to the 
476 
hotel admission to verify the following information: 
477 
• Inquire about any changes to the participant’s medical history 
478 
• Inquire about the participant’s self-quarantine, possible COVID exposures, and study-
479 
related initial COVID Testing. 
480 
• Study equipment (e.g. CGM and activity tracker) initiation has occurred 
481 
• Determine pump profile(s) the participant uses on certain days 
482 
• New CGM sensor has been placed approximately 24-72 hours prior to admission for 
483 
proper warm-up 
484 
• Verify with the participant that the goal CGM reading at time of arrival is less than 200 
485 
mg/dL; this may require contact with the study physician prior to arrival on the day of the 
486 
study visit  
487 

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• Should any concerns regarding medical history, pump information, or unforeseen issues 
488 
arise, the admission will be cancelled for that participant at the discretion of the 
489 
investigator 
490 
 
491 
For the pilot study, one participant will be assessed at a time.  The participant will arrive at the 
492 
hotel or rented house “bubble” on the first day of the admission.  The study team will perform 
493 
vital signs and inquire about the participant’s self-quarantine, COVID Testing, and any changes to 
494 
the participant’s medical history.  Any changes to medical history will be communicated to the 
495 
medical physician to ensure continued eligibility and participation.   
496 
Participants will at this point have the second COVID Test administered. 
497 
A urine pregnancy test will be collected. The test must be negative for the participant to continue 
498 
with the study.  
499 
The subject’s CGM reading and ketone concentration will be recorded. In the event that the 
500 
participant’s CGM reading is not between 80-250 mg/dL or ketone concentration is ≥0.6 mmol/L 
501 
prior to initiation of the UVa AP system, the study physician may recommend additional insulin 
502 
dosing according to the participants’ usual doses. Study physician may elect to cancel 
503 
participant’s participation in the hotel admission if concerned about their medical safety.  This 
504 
participant will not be replaced.  
505 
The participant’s home insulin pump will be discontinued, and the study Tandem research insulin 
506 
pump will be initiated.  The study team will ensure the proper function of the CGM, insulin pump, 
507 
and activity tracker. The goal will be to initiate Closed Loop Control by approximately 3-4 pm, 
508 
running the RocketAP system and the DiAs platform.  
509 
The CGM used in the study is FDA-approved for the non-adjunctive measurement of blood 
510 
glucose (i.e. the CGM reading can be used for insulin dosing decisions). The CGM readings will be 
511 
the primary source of blood glucose values.  There are no protocol fingerstick blood glucose 
512 
measurements other than at times of CGM calibration (if necessary) and if directed by the study 
513 
team.  
514 
 
515 
  The study physician will suggest appropriate treatment If CGM is <70 mg/dL or >250 mg/dL, or 
516 
ketone test is >0.6 mmol/L.  The study team may request fingersticks as needed. The study 
517 
subject may continue participation in the trial once CGM is between 70-250 mg /dL and ketone 
518 
concentration is ≤0.6 mmol/L. 
519 

CLINICAL PROTOCOL 
 
 
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If CGM is >250 for more than 3 hours or >400 mg/dL at any time, study physician will be notified, 
520 
and ketones will be checked. If ketone concentration is >0.6 mmol/L, the study team will check 
521 
the insulin pump infusion site and correction insulin will be administered per study physician 
522 
judgement via the subject’s insulin pump. The study team will monitor CGM changes and ketones 
523 
will be checked every 60 minutes until ketone concentration is ≤0.6 mmol/L.  If ketone 
524 
concentration is ≥3.0 mmol/L, the study physician will recommend the appropriate medical 
525 
treatment.    
526 
If CGM <60 mg/dL at any time, subjects will be given approximately 8-16 grams of fast-acting 
527 
rescue carbohydrates.  Study team will monitor CGM rise and will consider treating again if CGM 
528 
<80 mg/dL after approximately 20 minutes. Hypoglycemic treatments can occur at any time per 
529 
study physician request. 
530 
 
531 
Participants will eat a structured dinner at approximately 6-7 pm during the admission. The 
532 
participant will not announce carbohydrate ingestion, allowing testing of the Meal Control 
533 
Module on the RocketAP. During the time outside of the Study Dinner Sessions will continue in 
534 
closed loop mode until it is time for discharge.  
535 
 
536 
Participants will be free to engage in low-intensity activity (i.e. walking, kicking soccer ball) during 
537 
the admission. Participants will enjoy quiet activities in the evening. 
538 
 
539 
Discharge will be at approximately 8 a.m. If the CGM values are above 300 mg/dL and ketone 
540 
values are >0.6 mmol/L, the study team will check the insulin pump infusion site and correction 
541 
insulin will be administered per study physician judgement via the subject’s insulin pump.    
542 
Participants will be asked to continue monitoring ketone levels for 24-48 hours after the hotel 
543 
admission if ketones were present at time of discharge. Urine ketone supplies may be provided 
544 
for this testing.  
545 
 
546 
Approximately 24-48 hours after the hotel admission, the study team will contact the participant 
547 
via phone/email/text/text to assess adverse events, adverse device effects, and device issues 
548 

CLINICAL PROTOCOL 
 
 
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549 
At the conclusion of the Pilot Study, the medical monitor will review the data as referenced in 
550 
Chapter 9.   
551 

CLINICAL PROTOCOL 
 
 
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Chapter 7  Main Study  
552 
Main Study participants will participate in two hotel admissions. Each admission will be up to 90 
553 
hours in duration. The two study admissions should be less than 8 weeks apart. The study 
554 
physician will need to determine if second admission can be completed if greater than 8 weeks 
555 
from the first admission.  
556 
 
557 
Participants who are not familiar with the Dexcom G6 CGM will wear the equipment at home for 
558 
approximately 14 days to ensure proper use of the equipment during the two hotel admissions. 
559 
Other participants will immediately proceed to the hotel admissions.  
560 
 
561 
There will be at least three study staff present at all times at the study site, at least one of whom 
562 
will be clinical staff (e.g. nurse, physician, nurse practitioner). There will be a physician inside the 
563 
“bubble” during the study at all times.  In addition, at least one senior engineer will be on call 
564 
during the entire admission. Glucagon for the emergency treatment of hypoglycemia will be 
565 
available on-site. 
566 
 
567 
Participants will be contacted by the study team approximately 24-48 hours prior to each hotel 
568 
admission if most recent contact with than study participant exceeds 10 days. This is in addition 
569 
to the COVID testing for participants. The study team will verify the following information: 
570 
• Inquire about any changes to the participant’s medical history 
571 
• Confirm participant has self-quarantined and study-related initial COVID testing.  
572 
• Study equipment (e.g. CGM and activity tracker) initiation has occurred 
573 
• Determine pump profile(s) the participant uses on certain days 
574 
• New CGM sensor has been placed approximately 24-72 hours prior to admission for 
575 
proper warm-up 
576 
• Verify with the subject that the goal CGM reading at time of arrival is less than 200 mg/dL; 
577 
this may require contact with the study physician prior to arrival on the day of the study 
578 
visit  
579 

CLINICAL PROTOCOL 
 
 
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• Should any concerns regarding medical history, pump information, or unforeseen issues 
580 
arise, the admission will be cancelled for that participant at the discretion of the 
581 
investigator 
582 
 
583 
Participants will arrive at the hotel “bubble” on the first day of the admission.  As described in 
584 
section 10.3, all participants will receive a second test for COVID-19 after arriving for the stduy.  
585 
The study personnel will wear N95 masks and goggles when less than 6 feet from participants 
586 
until this COVID test returns negative.  The study team will perform vital signs and inquire about 
587 
any changes to the participant’s medical history.  Any changes to medical history will be 
588 
communicated to the medical physician to ensure continued eligibility and participation.   
589 
A urine pregnancy test will be collected. The test must be negative for the participant to continue 
590 
with the study.  
591 
The subject’s CGM reading and ketone concentration will be recorded. In the event that the 
592 
participant’s CGM reading is not between 80-250 mg/dL or ketone concentration is ≥0.6 mmol/L 
593 
prior to initiation of the UVa artificial pancreas system, the study physician may recommended 
594 
additional insulin dosing according to the participants’ usual doses. Study physician may elect to 
595 
cancel participant’s participation in the hotel admission if concerned about their medical safety.  
596 
This participant will not be replaced.  
597 
The participant’s home insulin pump will be discontinued, and the study insulin pump will be 
598 
initiated.  The study team will ensure the proper function of the CGM, insulin pump, and activity 
599 
tracker.  
600 
The CGM used in the study is FDA-approved for the non-adjunctive measurement of blood 
601 
glucose (i.e. the CGM reading can be used for insulin dosing decisions). The CGM readings will be 
602 
the primary source of blood glucose values.  There are no protocol fingerstick blood glucose 
603 
measurements other than at times of CGM calibration (if necessary) and if directed by the study 
604 
team.  Glycemic Treatment Guidelines to be used during the hotel admission are defined in 
605 
Chapter 8. 
606 
 
607 
The study physician will suggest appropriate treatment If CGM is <70 mg/dL or >250 mg/dL, or 
608 
ketone test is >0.6 mmol/L.  The study team may request fingersticks as needed. The study 
609 
subject may continue participation in the trial once CGM is between 70-250 mg /dL and ketone 
610 
concentration is ≤0.6 mmol/L. 
611 

CLINICAL PROTOCOL 
 
 
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If CGM is >250 for more than 3 hours or >400 mg/dL at any time, study physician will be notified 
612 
and ketones will be checked.  If ketone concentration is >0.6 mmol/L, the study team will check 
613 
the insulin pump infusion site and correction insulin will be administered per study physician 
614 
judgement via the subject’s insulin pump.  The study team will monitor CGM changes and ketones 
615 
will be checked every 60 minutes until ketone concentration is ≤0.6 mmol/L.  If ketone 
616 
concentration is ≥3.0 mmol/L, the study physician will recommend the appropriate medical 
617 
treatment.    
618 
If CGM <60 mg/dL at any time, subjects will be given approximately 8-16 grams of fast-acting 
619 
rescue carbohydrates.  Study team will monitor CGM rise and will consider treating again if CGM 
620 
<80 mg/dL after approximately 20 minutes.  Hypoglycemic treatments can occur at any time per 
621 
study physician request. 
622 
 
623 
Study Dinner Sessions start approximately 3-4 hours before the participant eats dinner and will 
624 
continue for approximately 12 hours after the dinner. Participants will eat a structured dinner at 
625 
approximately 6-7 pm during the admission. The order of the AP system tested (RocketAP vs. 
626 
Control-IQ) is determined randomly. The order of carbohydrate (CHO) announcement will be the 
627 
same in both cases (Table 1).  
628 
• Study Dinner Session #1 and #3:  Normal CHO announcement 
629 
• Study Dinner Session #2 and #4:  No announced CHO (Meal Control Module)  
630 
Blood glucose levels will be followed via continuous glucose monitor with the goal of maintaining 
631 
a blood glucose range 70-180 mg/dL during the 6 hours following start of the meal. The closed 
632 
loop session run between 3pm – 6 am and will be discontinued prior to time of discharge.  
633 
Breakfast and lunch will be announced into each system during the hotel admissions.  
634 
 
635 
Participants will be free to engage in low-intensity activity (i.e. walking, kicking soccer ball) during 
636 
the hotel admission. If COVID precaution milestones are met (all participants and on-site study 
637 
personnel are found to be COVID-negative on second study COVID test performed at entrance to 
638 
the “bubble,” see Section 10.3), limited activities with safe distancing and mask use may occur as 
639 
described in Section 10.3. Participants will enjoy quiet activities in the evening. 
640 

CLINICAL PROTOCOL 
 
 
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641 
Discharge will be at approximately 8 a.m. If the CGM values are above 300 mg/dL and ketone 
642 
values are >0.6 mmol/L, the study team will check the insulin pump infusion site and correction 
643 
insulin will be administered per study physician judgement via the subject’s insulin pump.    
644 
Participants will be asked to continue monitoring ketone levels for 24-48 hours after the hotel 
645 
admission if ketones were present at time of discharge. Urine ketone supplies may be provided 
646 
for this testing.  
647 
 
648 
Participants will complete questionnaire(s) at the completion of each admission. Questionnaires 
649 
are described in section 9.2. 
650 
 
651 
Approximately 24-48 hours after the hotel admission, the study team will contact the participant 
652 
via phone/email/text to assess adverse events, adverse device effects, and device issues Medical 
653 
Monitor Review 
654 
 
655 
At the conclusion of the Pilot Study, the medical monitor will review the data as referenced in 
656 
section 8.3.   
 
657 

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Chapter 8  Medical Monitor Review  
658 
 
659 
The Medical Monitor will be provided all adverse event data from the Pilot Study for review prior 
660 
to the main study.  The Medical Monitor will review data related to individual stopping criteria 
661 
as detailed in the study protocol.   
662 
 
663 
After review, the Medical Monitor can recommend that the current study continue without 
664 
modification, continue with specified modifications, discontinue one or more arms of the study, 
665 
or halt or modify the study until more information is available. 
666 
The Medical Monitor may recommend modifications to individual stopping rules if additional 
667 
safety concerns arise during from their continuing reviews of the study data.   
668 
The hotel admission will not be repeated unless required by the Medical Monitor.   
669 
 
670 
A Medical Monitor will review compiled safety data at the conclusion of the trial. In addition, the 
671 
Medical Monitor will review all DKA and severe hypoglycemia irrespective of relatedness to study 
672 
device use, and all serious events (including UADEs) related to study device use at the time of 
673 
occurrence. The Medical Monitor also will be informed of any ADEs not meeting criteria for a 
674 
UADE if the Study PI requests the Medical Monitor review.  The Medical Monitor can request 
675 
modifications to the study protocol or suspension or outright stoppage of the study if deemed 
676 
necessary based on the totality of safety data available. 
 
677 

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Chapter 9  Testing Procedures 
678 
 
679 
 HbA1c  
680 
• A blood sample will be obtained at screening to obtain a baseline hemoglobin A1c level. 
681 
Blood test may be obtained within 2 weeks prior to enrollment may be used for eligibility 
682 
purposes. 
683 
• HbA1c level may be measured by study team using the DCA2000, a comparable point of 
684 
care device, at time of screening  
685 
• Labs may be obtained at a local laboratory (e.g. LabCorp) convenient to the participant. 
686 
 Pregnancy Test 
687 
• A serum or urine pregnancy test will be required for women of childbearing potential at 
688 
in person visit and admission.  Test must be negative to participate in the study.  
689 
 
690 
The Demographic Data Survey will be asked at only the screening appointment and will reflect 
691 
the status of the adolescent participant.  
692 
Participants will be provided a short questionnaire asking them to rate their experience with the 
693 
study equipment.  
 
694 

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Chapter 10 Risks Associated with Clinical Trial 
695 
 
696 
Risks and Benefits are detailed below. Loss of confidentiality is a potential risk; however, data are 
697 
handled to minimize this risk. Hypoglycemia, hyperglycemia and ketone formation are always a 
698 
risk in participants with type 1 diabetes and participants will be monitored for these symptoms.  
699 
 Venipuncture Risks 
700 
A hollow needle/plastic tube may be placed in the arm for taking blood samples (e.g. external 
701 
HbA1c measurements for inclusion criteria). Blood draws can cause some common reactions like 
702 
pain, bruising, or redness at the sampling site.  Less common reactions include bleeding from the 
703 
sampling site, formation of a small blood clot or swelling of the vein and surrounding tissues, and 
704 
fainting. 
705 
 Fingerstick Risks 
706 
About 1 drop of blood will be removed by fingerstick for measuring blood sugars and sometimes 
707 
HbA1c or other tests. This is a standard method used to obtain blood for routine hospital 
708 
laboratory tests.  Pain is common at the time of lancing.  In about 1 in 10 cases, a small amount 
709 
of bleeding under the skin will produce a bruise. A small scar may persist for several weeks. The 
710 
risk of local infection is less than 1 in 1000. This should not be a significant contributor to risks in 
711 
this study as finger sticks are part of the usual care for people with diabetes. 
712 
 Subcutaneous Catheter Risks (CGM) 
713 
Participants using the CGM will be at low risk for developing a local skin infection at the site of 
714 
the sensor needle placement. If a catheter is left under the skin for more than 24 hours it is 
715 
possible to get an infection where it goes into the skin, with swelling, redness and pain.  There 
716 
may be bleeding where the catheter is put in and bleeding under the skin causes a bruise (1 in 10 
717 
risk). 
718 
Study staff should verbally alert the participant that on rare occasions, the CGM may break and 
719 
leave a small portion of the sensor under the skin that may cause redness, swelling, or pain at 
720 
the insertion site. The participant should be further instructed to notify the study coordinator 
721 
immediately if this occurs. 
722 
 Risks of Hypoglycemia  
723 
As with any person having type 1 diabetes and using insulin, there is always a risk of having a low 
724 
blood sugar (hypoglycemia). The frequency of hypoglycemia should be no more and possibly less 
725 

CLINICAL PROTOCOL 
 
 
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than it would be as part of daily living. Symptoms of hypoglycemia can include sweating, 
726 
jitteriness, and not feeling well.  Just as at home, there is the possibility of fainting or seizures 
727 
(convulsions) and that for a few days the participant may not be as aware of symptoms of 
728 
hypoglycemia.  A CGM functioning poorly and significantly over-reading glucose values could lead 
729 
to inappropriate insulin delivery. 
730 
 Risks of Hyperglycemia  
731 
Hyperglycemia is likely because of the study design including unannounced carbohydrate 
732 
ingestion.  Also, hyperglycemia and ketonemia could occur if insulin delivery is attenuated or 
733 
suspended for an extended period or if the pump or infusion set is not working properly.  A CGM 
734 
functioning poorly and significantly under-reading glucose values could lead to inappropriate 
735 
suspension of insulin delivery. 
736 
 Risks of Device Reuse  
737 
Participant will be informed that FDA or relevant national authorities have approved the insulin 
738 
pump, CGM, glucometer and ketone meter for single use and that by using them among multiple 
739 
patients, bloodborne pathogens (i.e. Hepatitis B) may be spread through the use of multiple 
740 
users. 
741 
The study CGM system is labelled for single use only. The sensor (the component of the system 
742 
that enters the skin) will be single use only. The transmitter and receiver may be reused during 
743 
the study after cleaning the device using a hospital-approved cleaning procedure. The transmitter 
744 
is attached to the sensor but does not enter the skin and the receiver, if used, is a handheld 
745 
device.  
746 
The study insulin pumps are labelled for single-patient use. During the study, this device may be 
747 
reused after cleaning adhering to a hospital-approved cleaning procedure. All infusion set 
748 
equipment will be single patient use only (infusion set insertion kits, tubing, cartridges etc.).   
749 
The study blood glucose meter and blood ketone meter are labelled for single-patient use. 
750 
During the study, these devices may be reused after cleaning adhering to a hospital-approved 
751 
cleaning procedure.   
752 
 Device Cleaning Instructions 
753 
CGM cleaning instructions are provided in the Dexcom G4 Platinum (Professional) Cleaning and 
754 
Disinfection manual (current edition) and a similar approach will be applied for the G6 version 
755 
used in this study. The transmitter should be cleaned with Clorox Healthcare® Bleach Germicidal 
756 
Cleaner or any disinfectant product in a spray bottle containing a bleach solution of 6500 parts 
757 
per million with the EPA registration number 56392-7.  The transmitter will be submerged in this 
758 

CLINICAL PROTOCOL 
 
 
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solution and then placed on an absorbent wipe or clean surface.  Two sprays will be dispensed 
759 
from the Clorox cleaner onto each side of the transmitter. A nylon brush will be used to scrub the 
760 
transmitter on all sides for 30 seconds.  The transmitter will be placed in the Clorox Cleaner 
761 
solution for one minute. Transmitter is then rinsed under flowing tap water for ten seconds. The 
762 
transmitter will then be disinfected using a disinfectant product with EPA registration number 
763 
56392-7 using similar procedures as the cleaning process.   
764 
Per the pump manufacturer, the insulin pump will be cleaned with a damp lint-free cloth. Use of 
765 
household or industrial cleaners, solvents, bleach, scouring pads, chemicals, or sharp instruments 
766 
are prohibited. The pump should never be submerged in water. If needed, use only a very mild 
767 
detergent, such as a bit of liquid soap with warm water. A soft towel will be used to dry the pump.  
768 
The Accu-Chek Guide glucometer is cleaned and disinfected with two separate Super Sani-Cloths 
769 
(EPA number 9480-4). The entire surface will be cleaned, making sure the surface stays wet for 2 
770 
minutes. This step is repeated with a clean cloth for disinfecting the device.  
771 
The Precision Xtra User’s Guide suggests that healthcare professionals use 10% bleach, 70% 
772 
alcohol or 10% ammonia to clean the device.  
773 
Equipment that touches intact skin will be cleaned with ethyl or isopropyl alcohol (70-90%), 
774 
quaternary ammonium germicidal detergent (i.e. Cavicide, EPA number 46781) or household 
775 
bleach. The contact time on the surface depends on the method used to clean the equipment. 
776 
Cavicide requires three minutes on the surface of the equipment. Clorox Germicidal Bleach Wipes 
777 
require two minutes on the equipment. The surface should remain wet (i.e. slightly damp) with 
778 
the disinfectant to be considered effective though not wet enough to leave drops of liquid.  
779 
In the event a manufacturer updates cleaning procedures for their device, the study team will 
780 
adhere to the most current recommendations.  
781 
There is the risk of blood sampling collection and contamination from sampling techniques. Hand 
782 
washing with either soap & water or waterless hand sanitizer will be used prior to caring for the 
783 
study subject. Gloves will be worn during blood sample collection and processing. Medical 
784 
personnel will continue to practice hygiene for the subject’s protection (i.e. hand washing, 
785 
changing gloves frequently, disposing needles properly). Gloves will be removed and hands 
786 
washed or sanitized prior to leaving and upon return to the subject’s room. Soiled linen will be 
787 
changed to minimize the transfer of pathogenic organisms. 
788 
 Hb1Ac Risk 
789 
An NGSP Point of Care analyzer (i.e. DCA Vantage Analyzer) will be utilized at the research site to 
790 
obtain the subject’s HbA1c level. 
791 

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 Other Risks  
792 
Some participants may develop skin irritation or allergic reactions to the adhesives used to secure 
793 
the CGM, or to secure the insulin infusion sets for the continuous subcutaneous insulin infusion.  
794 
If these reactions occur, different adhesives or “under-taping” (such as with IV 3000, Tegaderm, 
795 
etc.) will be tried, sites will be rotated frequently, and a mild topical steroid cream or other 
796 
medication may be required. 
797 
Whenever the skin is broken there is the possibility of an infection.  The CGM and pump infusion 
798 
sites are inserted under the skin.  It is possible that any part that is inserted under the skin may 
799 
cause an infection.  These occur very infrequently, but, if an infection was to occur, oral and/or 
800 
topical antibiotics can be used.  The risk of skin problems could be greater if you use a sensor for 
801 
longer than it is supposed to be used.  Therefore, participants will be carefully instructed about 
802 
proper use of the sensor. 
803 
Data downloaded from the CGM, pump, glucometer, and ketone meter will be collected for the 
804 
study as measures of diabetes self-management behaviors. Some people may be uncomfortable 
805 
with the researchers' having such detailed information about their daily diabetes habits. 
806 
 Known Potential Benefits  
807 
It is expected that this protocol will yield increased knowledge about using an automated closed-
808 
loop system with anticipatory action to control glucose levels. The individual participant may not 
809 
benefit from study participation. 
810 
 Risk Assessment 
811 
Based on the facts that (1) adults and adolescents with diabetes experience mild hypoglycemia 
812 
and hyperglycemia frequently as a consequence of the disease and its management, (2) the study 
813 
intervention involves periodic automated insulin dosing that may increase the likelihood of 
814 
hypoglycemia, and periodic automated attenuation of insulin delivery that may increase the 
815 
likelihood of hyperglycemia, (3) mitigations are in place, and have been tested in prior studies 
816 
using the investigational device system in the home setting, that limit the likelihood of excessive 
817 
insulin dosing or prolonged withdrawal of insulin, and (4) rapid reversal of hypoglycemia and 
818 
hyperglycemia can be achieved, it is the assessment of the investigators that this protocol falls 
819 
under DHHS 46.405 which is a minor increase over minimal risk. In addition, it is the belief of the 
820 
investigators that this study also presents prospect of direct benefit to the participants and 
821 
general benefit to others with diabetes. 
822 
 
823 

CLINICAL PROTOCOL 
 
 
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824 
The study is being conducted in compliance with the policies described in the study policies 
825 
document, with the ethical principles that have their origin in the Declaration of Helsinki, with 
826 
the protocol described herein, and with the standards of Good Clinical Practice (GCP). 
827 
Whenever possible, data will be directly collected in electronic case report forms, which will be 
828 
considered the source data. 
829 
The protocol is considered a significant risk device study, due to the fact that the closed loop 
830 
system is experimental.  Therefore, an investigational device exemption (IDE) from the U.S. Food 
831 
and Drug Administration (FDA) is required to conduct the study. 
832 
 
833 
To mitigate risk of exposure to COVID 19,  we will attempt to create a COVID-free “bubble.”.  This 
834 
plan involves renting an entire floor of a hotel for study purposes only and taking steps to only 
835 
allow entrance to those who are reasonably likely to be COVID-free (participants and study 
836 
personnel) and protecting a COVID-free space in which they can stay (Environment).  
837 
Acknowledging that zero risk is not possible, we seek to take steps that in almost every case 
838 
exceed the protection offered by the standard-of-care for clinical care and other research 
839 
activities—and that very likely is safer than the usual activities of these adolescents, who in their 
840 
current daily lives go to stores, participate in activities with friends, and in many cases attend 
841 
school.  Because of the restrictions that we will require, and testing we will employ, the 
842 
participants are likely to be at lower risk for COVID transmission (during the study) than if they 
843 
were pursuing their usual daily lives. 
844 
        Participants and Study Personnel 
845 
We will follow a combination of self-isolation and testing to increase our likelihood of having all 
846 
COVID-free entrants into the “bubble.”    
847 
 
848 
Figure 2: COVID Precautionary Timeline 
849 

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As shown in the Figure 2 : 
850 
1. Participants will agree to stay quarantine for at least five days before being tested. This 
851 
ensures that participants will be tested at least five days after their last possible exposure. 
852 
“Quarantine” (or variations of this word) will be defined as: staying home with no close 
853 
contact for more than 15 minutes, or contact only with an N95 or equivalent mask, with 
854 
anyone who might have been exposed to COVID. Participants must get a nasal swab PCR 
855 
test, this may be done at UVA or in their community. 
856 
2. All participants will be ineligible if they have had known COVID exposure or symptoms 
857 
within 14 days of study start.  
858 
3. All participants, staff (research coordinators, technicians), nurses and physicians will be 
859 
tested with a COVID PCR test 48-72 hours before being admitted to the study hotel.  Those 
860 
with positive tests will be excluded from the study.  Participants will continue to self-
861 
quarantine in the time between testing and being admitted to the hotel. (This self-
862 
quarantine and testing regimen is well beyond the standard-of-care for current clinical 
863 
care and most other research interactions, both of which involve repeated interactions 
864 
with patients/participants who have neither self-isolated nor been tested for COVID.)    
865 
4. Upon admission to the hotel, all participants and staff will receive a second COVID PCR 
866 
test.  Following this test, all participants will stay quarantined in their hotel room without 
867 
leaving until this second test returns negative.  Until the second COVID tests return 
868 
negative, all study staff who have to come within 6 feet of participants will wear N95 
869 
masks and goggles when doing so. 
870 
5. Any participants with positive test will be discharged from the study.  Hotel rooms of 
871 
these participants will not be used further. We will limit any personal interaction between 
872 
study personnel and these individuals.  Any interaction will be with N95 masks, hospital 
873 
gown, gloves, and goggles. Study personnel will immediately change (and not reuse these 
874 
clothes) and shower. 
875 
6. Participants will only share a room with a sibling or housemate that they are currently 
876 
living with; otherwise, they must be alone in a room. 
877 
7. Study staff and physicians will stay in the “bubble” with the participants.  The study team 
878 
includes 2 study coordinator, 1 technician, 2 study physicians.  Nurses will be assigned to 
879 
shifts of up to 12 hours; there will be a minimum of 2 nurses on site at all times (and thus 
880 
a total of 6 study personnel total).  We anticipate up to 20 study participants in the 
881 
“bubble.”  As described above, study staff that will be onsite will have COVID 19 negative 
882 
test within 48-72 hours of the admission. All study staff onsite will abide by UVa clinical 
883 
protocols currently in place for healthcare workers which stands as the standard-of care 
884 
for those involved in patient care.  This protocol includes use of the HOOS Health Check 
885 
app and using masks at all times when with any other individual (participants or other 
886 
study personnel). To minimize the number of staff members required to be present for 
887 

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the study, monitoring of study equipment will be performed remotely.  Remote and on-
888 
site staff will communicate via a dedicated study phone.   
889 
8. Because of the precautions we have put in place, we do not anticipate that participants 
890 
or study personnel will have COVID during the study.  However, participants or study 
891 
personnel who develop symptoms of COVID during the study will be discharged from the 
892 
“bubble” and receive COVID testing.  In the case of study personnel, back-up team 
893 
members who have received a negative COVID test hotel admission will replace the 
894 
member who developed symptoms. 
895 
  
Environment 
896 
We are working to reduce risk of COVID exposure both by decreasing coronavirus on surfaces 
897 
and avoiding any contact with hotel personnel.  To do so, we will take the following 
898 
precautions: 
899 
1. We will reserve the entire study floor of the hotel starting at least 24 hours before 
900 
admission.  While the rooms will have already been cleaned with the hotel’s cleaning 
901 
protocol, keeping the rooms empty for 24 hours further allows time for inactivation of 
902 
any coronavirus.  (This goes beyond the standard-of-care for clinical care and other 
903 
research activities, which repeatedly utilize spaces throughout the day such as exam 
904 
rooms and elevators, with cleaning of some surfaces but without allowing for inactivation 
905 
of potential coronavirus on other surfaces not cleaned.) 
906 
2. We will further clean the surfaces of each hotel room with disinfectant wipes before 
907 
participants are admitted.  
908 
3. The lobby of the hotel will be avoided, instead using the back stairwell.  We will verify that 
909 
there are no other users of the stairwell before using it. 
910 
4. Hotel staff will be instructed to avoid entrance to the study floor during the entirety of 
911 
the stay. Housekeeping activities will be cancelled during the study.  The only exception 
912 
is breakfast delivery, which will be delivered by hotel staff in bags, either via the back 
913 
stairwell and left on the floor at the entrance to the stairs or on the elevator and left right 
914 
in front of the elevator (without having to step onto the study floor).   
915 
5. If hotel staff absolutely have to enter the floor for any purpose (e.g. plumbing failure), 
916 
they will be requested to notify study personnel by phone before entering the study floor 
917 
and will be asked to wear masks at all times while on the floor.  If they need to enter a 
918 
participant’s room, the participant will first leave to a safe room.  Following the hotel staff 
919 
work, the participant’s room will receive a thorough wipe by study staff before the 
920 
participant can return. 
921 
6. Additional food will be dropped off by study staff (not in the hotel “bubble”) via the back 
922 
stairwell, and left on the floor. 
923 

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7. Food will then be delivered one room at a time to individual participants by on-site study 
924 
staff.  Participants will eat their food in their rooms. 
925 
 Activities 
926 
Group activities are important for this study, both for the physical activity (which is an 
927 
important part of healthy diabetes control) and because of the otherwise completely 
928 
confined space that constitutes the study.  Again, we seek to only pursue safe situations that 
929 
meet or exceed what is currently allowed inside the UVa Health System for faculty, staff, 
930 
students and visitors. (For example, Internal Medicine Grand Rounds is permitted inside, in-
931 
person, with spacing and mask use—but does not require the self-isolating and testing that 
932 
we will employ).   
933 
1. There will be no group activities until all COVID tests performed at study entry have 
934 
returned negative. Study personnel will wear 95 masks during this period. 
935 
2. Group activities will involve the following precautions: 
936 
o Study personnel will be stationed at intervals within the group to supervise that 
937 
participants remain separated by 6 feet at all times. 
938 
o Use of masks will be required by study staff and participants at all times. 
939 
Participants caught without a mask during any part of the activity will be escorted 
940 
back to the hotel and will not be able to participate in subsequent activities. 
941 
o We will always use the back stairwell (not elevator, not lobby) to exit hotel. 
942 
o We will utilize a staggered exit so that participants are always at least 6 feet 
943 
separated from each other.   
944 
o Walking will be the only form of transportation. 
945 
o Preference for outdoor activities (e.g., walking, kicking soccer ball) will always be 
946 
sought. 
947 
o We will avoid congested areas where distancing is not possible.   
948 
o Any indoor activities will be only be in a UVa facility that has been wiped down 
949 
before use and has adequate space to permit separation by at least 6 feet 
950 
between individuals at all times. Study staff will be present to observe and verify 
951 
that all participants keep masks on and keep distanced.  Entrance to the space 
952 
will be via the shortest distance to the facility (e.g., direct entrance from outside 
953 
or very short hallway that will only be used when there are no other individuals 
954 
in the hallway. 
955 
All activities will abide by statewide restrictions on numbers of individuals 
956 
together. 
957 
o  
958 
 
 
959 

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Chapter 11   Adverse Events, Device Issues, and Stopping Rules 
960 
 
961 
 Adverse Events (AE) 
962 
Any untoward medical occurrence in a study participant, irrespective of the relationship between 
963 
the adverse event and the device(s) under investigation (section 11.2) for reportable adverse 
964 
events for this protocol). 
965 
 Serious Adverse Event (SAE) 
966 
 Any untoward medical occurrence that: 
967 
• Results in death. 
968 
• Is life-threatening; (a non-life-threatening event which, had it been more severe, might 
969 
have become life-threatening, is not necessarily considered a serious adverse event). 
970 
• Requires inpatient hospitalization or prolongation of existing hospitalization. 
971 
• Results in persistent or significant disability/incapacity or substantial disruption of the 
972 
ability to conduct normal life functions (life threatening). 
973 
• Is a congenital anomaly or birth defect. 
974 
• Is considered a significant medical event by the investigator based on medical judgment 
975 
(e.g., may jeopardize the participant or may require medical/surgical intervention to 
976 
prevent one of the outcomes listed above). 
977 
 Unanticipated Adverse Device Effect (UADE) 
978 
Any serious adverse effect on health or safety or any life-threatening problem or death caused 
979 
by, or associated with, a device, if that effect, problem, or death was not previously identified in 
980 
nature, severity, or degree of incidence in the investigational plan or application (including a 
981 
supplementary plan or application), or any other unanticipated serious problem associated with 
982 
a device that relates to the rights, safety, or welfare of participants (21 CFR 812.3(s)). 
983 
 Adverse Device Effect (ADE) 
984 
Any untoward medical occurrence in a study participant which the device may have caused or to 
985 
which the device may have contributed. 
986 

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 Device Complaints and Malfunctions 
987 
A device complication or complaint is something that happens to a device or related to device 
988 
performance, whereas an adverse event happens to a participant. A device complaint may occur 
989 
independently from an AE, or along with an AE. An AE may occur without a device complaint or 
990 
there may be an AE related to a device complaint.  A device malfunction is any failure of a device 
991 
to meet its performance specifications or otherwise perform as intended.  Performance 
992 
specifications include all claims made in the labeling for the device.  The intended performance 
993 
of a device refers to the intended use for which the device is labeled or marketed. (21 CFR 803.3).   
994 
 
995 
For this protocol, a reportable adverse event includes any untoward medical occurrence that 
996 
meets one of the following criteria: 
997 
• A serious adverse event as defined in section 11.2 
998 
• An Adverse Device Effect as defined in section 11.1.4, unless excluded from reporting in 
999 
section 11.7 
1000 
• An Adverse Event as defined in section 11.1.1 occurring in association with a study 
1001 
procedure 
1002 
• An AE as defined in section 11.1.1 which leads to discontinuation of a study device for 2 
1003 
or more hours 
1004 
• Hypoglycemia meeting the definition of severe hypoglycemia as defined in section 11.2.1  
1005 
• Diabetic ketoacidosis (DKA) as defined in section 11.2.2 or in the absence of DKA, a 
1006 
hyperglycemic or ketosis event meeting the criteria defined below 
1007 
Hypoglycemia and hyperglycemia not meeting the criteria below will not be recorded as adverse 
1008 
events unless associated with an Adverse Device Effect. Skin reactions from sensor placement 
1009 
are only reportable if severe and/or required treatment. 
1010 
 Hypoglycemia Event 
1011 
Hypoglycemia not associated with an Adverse Device Effect is only reportable as an adverse event 
1012 
when the following definition for severe hypoglycemia is met:   
1013 
• the event required assistance of another person due to altered consciousness, and 
1014 
required another person to actively administer carbohydrate, glucagon, or other 
1015 
resuscitative actions 
1016 

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• impaired cognitively to the point that he/she was unable to treat himself/herself, was 
1017 
unable to verbalize his/ her needs, was incoherent, disoriented, and/or combative, or 
1018 
experienced seizure or coma. These episodes may be associated with sufficient 
1019 
neuroglycopenia to induce seizure or coma 
1020 
• if plasma glucose measurements are not available during such an event, neurological 
1021 
recovery attributable to the restoration of plasma glucose to normal is considered 
1022 
sufficient evidence that the event was induced by a low plasma glucose concentration 
1023 
 Hyperglycemia Events/Diabetes Ketoacidosis 
1024 
Hyperglycemia not associated with an Adverse Device Effect is only reportable as an adverse 
1025 
event when one of the following four criteria is met:  
1026 
• the event involved DKA, as defined by the Diabetes Control and Complications Trial 
1027 
(DCCT) and described below evaluation or treatment was obtained at a health care 
1028 
provider facility for an acute event involving hyperglycemia or ketosis 
1029 
• blood ketone level ≥1.5 mmol/L and communication occurred with a health care provider 
1030 
at the time of the event 
1031 
• blood ketone level ≥3.0 mmol/L, even if there was no communication with a health care 
1032 
provider 
1033 
Hyperglycemic events are classified as DKA if the following are present: 
1034 
• Symptoms such as polyuria, polydipsia, nausea, or vomiting 
1035 
• blood ketones ≥1.5 mmol/L or large/moderate urine ketones 
1036 
• Treatment provided in a health care facility 
1037 
All reportable Adverse Events—whether volunteered by the participant, discovered by study 
1038 
personnel during questioning, or detected through physical examination, laboratory test, or 
1039 
other means—will be reported on an adverse event form online.  Each adverse event form is 
1040 
reviewed by the Medical Monitor to verify the coding and the reporting that is required. 
1041 
 
1042 
The study investigator will assess the relationship of any adverse event to be related or unrelated 
1043 
by determining if there is a reasonable possibility that the adverse event may have been caused 
1044 
by the study device. 
1045 

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To ensure consistency of adverse event causality assessments, investigators should apply the 
1046 
following general guideline when determining whether an adverse event is related: 
1047 
• There is a plausible temporal relationship between the onset of the adverse event and 
1048 
the study intervention, and the adverse event cannot be readily explained by the 
1049 
participant’s clinical state, intercurrent illness, or concomitant therapies; and/or the 
1050 
adverse event follows a known pattern of response to the study intervention; and/or the 
1051 
adverse event abates or resolves upon discontinuation of the study intervention or dose 
1052 
reduction and, if applicable, reappears upon re-challenge. 
1053 
• Evidence exists that the adverse event has an etiology other than the study intervention 
1054 
(e.g., preexisting medical condition, underlying disease, intercurrent illness, or 
1055 
concomitant medication); and/or the adverse event has no plausible temporal 
1056 
relationship to study intervention. 
1057 
 
1058 
While we are taking significant steps to prevent transmission of COVID-19 during this study, there 
1059 
is a possibility that participants, based either on exposure before the hotel admission or during 
1060 
the stay, are infected with COVID-19.  Infection with COVID-19 could be determined by testing 
1061 
48-hours prior to study admission (in which case would be deemed not related to the study), 
1062 
testing at arrival to the hotel (again not related) or onset of new symptoms during the stay. The 
1063 
probability that infection is related to the study may be inferred in part by the timing, with 
1064 
symptoms beginning on day 1 or 2 of the study being more likely not related and onset of 
1065 
symptoms afterward being possibly related to exposure during the study.  Any appearance of 
1066 
COVID symptoms in participants will be cause for repeat COVID testing and quarantine until test 
1067 
results are returned.  If the  positive, the participants will be discharged from the study. Study 
1068 
team will use N95 masks, gown, gloves, and goggles until test results are returned.  
1069 
In the event of a COVID positive test in a participant, the study team will follow up with the 
1070 
participant via phone until conclusion of treatment for the COVID related symptoms. All 
1071 
participants will be asked to follow up via phone with the study team in the event of a positive 
1072 
test within 14 days after discharge from the hotel.  
1073 
 
1074 
The intensity of an adverse event will be rated on a three-point scale: (1) mild, (2) moderate, or 
1075 
(3) severe. It is emphasized that the term severe is a measure of intensity: thus, a severe adverse 
1076 
event is not necessarily serious. For example, itching for several days may be rated as severe, but 
1077 
may not be clinically serious. 
1078 

CLINICAL PROTOCOL 
 
 
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• MILD: Usually transient, requires no special treatment, and does not interfere with the 
1079 
participant’s daily activities. 
1080 
• MODERATE: Usually causes a low level of inconvenience or concern to the participant and 
1081 
may interfere with daily activities but is usually ameliorated by simple therapeutic 
1082 
measures. 
1083 
• SEVERE: Interrupts a participant’s usual daily activities and generally requires systemic 
1084 
drug therapy or other treatment. 
1085 
 
1086 
Adverse events will be coded per the UVA IRB website instructions (i.e. mild, moderate, severe).  
1087 
The Medical Monitor will review the investigator’s assessment of causality and may agree or 
1088 
disagree.  Both the investigator’s and Medical Monitor’s assessments will be recorded.  The 
1089 
Medical Monitor will have the final say in determining the causality. 
1090 
Adverse events that continue after the participant’s discontinuation or completion of the study 
1091 
will be followed until their medical outcome is determined or until no further change in the 
1092 
condition is expected. 
1093 
 
1094 
The outcome of each reportable adverse event will be classified by the investigator as follows: 
1095 
• RECOVERED/RESOLVED – The participant recovered from the AE/SAE without sequelae.  
1096 
Record the AE/SAE stop date. 
1097 
• RECOVERED/RESOLVED WITH SEQUELAE – The event persisted and had stabilized without 
1098 
change in the event anticipated.  Record the AE/SAE stop date. 
1099 
• FATAL – A fatal outcome is defined as the SAE that resulted in death. Only the event that 
1100 
was the cause of death should be reported as fatal.  AEs/SAEs that were ongoing at the 
1101 
time of death; however, were not the cause of death, will be recorded as “resolved” at 
1102 
the time of death. 
1103 
• NOT RECOVERED/NOT RESOLVED (ONGOING) – An ongoing AE/SAE is defined as the 
1104 
event was ongoing with an undetermined outcome. 
1105 
• An ongoing outcome will require follow-up by the site in order to determine the final 
1106 
outcome of the AE/SAE. 
1107 

CLINICAL PROTOCOL 
 
 
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• The outcome of an ongoing event at the time of death that was not the cause of death, 
1108 
will be updated and recorded as “resolved” with the date of death recorded as the stop 
1109 
date. 
1110 
• UNKNOWN – An unknown outcome is defined as an inability to access the participant or 
1111 
the participant’s records to determine the outcome (for example, a participant that was 
1112 
lost to follow-up). 
1113 
All clinically significant abnormalities of clinical laboratory measurements or adverse events 
1114 
occurring during the study and continuing at study termination should be followed by the 
1115 
participant’s physician and evaluated with additional tests (if necessary) until diagnosis of the 
1116 
underlying cause, or resolution. Follow-up information should be recorded on source documents. 
1117 
If any reported adverse events are present when a participant completes the study, or if a 
1118 
participant is withdrawn from the study due to an adverse event, the participant will be 
1119 
contacted for re-evaluation within 2 weeks.  If the adverse event has not resolved, additional 
1120 
follow-up will be performed as appropriate.  Every effort should be made by the Investigator or 
1121 
delegate to contact the participant until the adverse event has resolved or stabilized. 
1122 
 
1123 
All UADEs, ADEs, device complaints, and device malfunctions will be reported irrespective of 
1124 
whether an adverse event occurred, except in the following circumstances. 
1125 
The following device issues are anticipated and will not be reported but will reported as an 
1126 
Adverse Event if the criteria for AE reporting described above are met: 
1127 
• Component disconnections 
1128 
• CGM sensors lasting fewer than the number of days expected per CGM labeling 
1129 
• CGM tape adherence issues 
1130 
• Pump infusion set occlusion not leading to ketosis 
1131 
• Battery lifespan deficiency due to inadequate charging or extensive wireless 
1132 
communication 
1133 
• Intermittent device component disconnections/communication failures not leading to 
1134 
system replacement 
1135 
• Device issues clearly addressed in the user guide manual that do not require additional 
1136 
troubleshooting 
1137 

CLINICAL PROTOCOL 
 
 
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• Skin reactions from CGM sensor placement or pump infusion set placement that do not 
1138 
meet criteria for AE reporting 
1139 
 
1140 
• UADEs must be reported within 10 working days to the FDA after the sponsor first 
1141 
receives notice of the adverse effect. 
1142 
• Other reportable adverse events, device malfunctions (with or without an adverse event) 
1143 
and device complaints should be reported promptly, but there is no formal required 
1144 
reporting period. 
1145 
• The IDE Sponsor will investigate the UADE and if indicated, report the results of the 
1146 
investigation to the IRBs, FDA, and DSMB within 10 working days of the study team 
1147 
becoming aware of the UADE per 21CFR 812.46(b) (2).  
1148 
• The Medical Monitor will determine if the UADE presents an unreasonable risk to 
1149 
participants. If so, the DSMB must ensure that all investigations, or parts of investigations 
1150 
presenting that risk, are terminated as soon as possible but no later than 5 working days 
1151 
after the Medical Monitor makes this determination and no later than 15 working days 
1152 
after first receipt notice of the UADE. 
1153 
• In the case of a device system component malfunction (e.g. pump, CGM, control 
1154 
algorithm), information will be forwarded to the responsible manufacturer by the study 
1155 
personnel. 
1156 
 
1157 
 Participant Discontinuation  
1158 
Rules for discontinuing study device use are described below. 
1159 
• The investigator believes it is unsafe for the participant to continue on the intervention.  
1160 
This could be due to the development of a new medical condition or worsening of an 
1161 
existing condition; or participant behavior contrary to the indications for use of the device 
1162 
that imposes on the participant’s safety 
1163 
• The participant requests that the treatment be stopped 
1164 
• The participant tests positive for COVID-19 on either of the two scheduled COVID-19 tests 
1165 
or subsequently develops symptoms for COVID-19 and tests positive. 
1166 
• Two distinct episodes of DKA, or one distinct episode of DKA attributable to study device 
1167 
use. 
1168 

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• Two distinct severe hypoglycemia events with BG <50 mg/dL and meeting the definition 
1169 
in section 11.2.1 of the protocol, or one distinct severe hypoglycemia event attributable 
1170 
to study device use, with BG <50mg/dL and meeting the definition in section 11.2.1 of the 
1171 
protocol. 
1172 
 Suspending/Stopping Overall Study 
1173 
In the case of an unanticipated system malfunction resulting in a severe hypoglycemia or severe 
1174 
hyperglycemia event (as defined in section 11.2.2), use of the study device system will be 
1175 
suspended while the problem is diagnosed. 
1176 
In addition, study activities could be similarly suspended if the manufacturer of any constituent 
1177 
study device requires stoppage of device use for safety reasons (e.g. product recall).  The affected 
1178 
study activities may resume if the underlying problem can be corrected by a protocol or system 
1179 
modification that will not invalidate the results obtained prior to suspension. The study Medical 
1180 
Monitor will review all adverse events and adverse device events that are reported during the 
1181 
study and will review compiled safety data at periodic intervals (generally timed to the review of 
1182 
compiled safety data by the Medical Monitor). The Medical Monitor may request suspension of 
1183 
study activities or stoppage of the study if deemed necessary based on the totality of safety data 
1184 
available. 
1185 
 
1186 
A Medical Monitor will review all DKA and severe hypoglycemia irrespective of relatedness to 
1187 
study device use, and all serious events (including UADEs) related to study device use at the time 
1188 
of occurrence. The Medical Monitor can request modifications to the study protocol or 
1189 
suspension or outright stoppage of the study if deemed necessary based on the totality of safety 
1190 
data available. Details regarding Medical Monitor review will be documented in a separate 
1191 
Medical Monitor document.   
1192 
 
1193 
A data breach is defined in the HITECH Act (43 USC 17932) as an unauthorized acquisition, access, 
1194 
or use of protected health information (PHI) that compromises the security or privacy of such 
1195 
information.  
 
1196 

CLINICAL PROTOCOL 
 
 
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Chapter 12 Miscellaneous Considerations  
1197 
 
1198 
Participants using glulisine at the time of enrollment will be asked to contact their personal 
1199 
physician to change their prescribed personal insulin to lispro or aspart for the duration of the 
1200 
trial. 
1201 
The study devices (study insulin pump, study CGM) must be removed before Magnetic Resonance 
1202 
Imaging (MRI), Computed Tomography (CT) or diathermy treatment. Participants may continue 
1203 
in the trial after temporarily discontinuing use if requiring one of the treatments above. 
1204 
 
1205 
Participation in the study is voluntary. Participant may withdraw at any time.  For participants 
1206 
who do withdraw from the study, the study team will determine if their data will be used in 
1207 
analysis.  
1208 
 
1209 
For security and confidentiality purposes, subjects will be assigned an identifier that will be used 
1210 
instead of their name.  Protected health information gathered for this study may be shared with 
1211 
the third-party collaborators.  De-identified subject information may also be provided to 
1212 
collaborators involved in the study after the appropriate research agreement has been executed. 
1213 

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Page 54 of 61 
 
Chapter 13 Statistical Consideration 
1214 
 
1215 
The  main study is itself a pilot study to assess glycemic responses to four different approaches 
1216 
to insulin dosing for carbohydrate ingestion, with two different AP systems (RocketAP and 
1217 
Control-IQ, in random order) each in sessions involving normal carbohydrate announcement and 
1218 
no carbohydrate announcement (on successive nights).  This information is detailed in Table 1.  
1219 
Randomization will occur via selection from the above list using permuted blocks in groups of 4, 
1220 
4 and 2.   
1221 
 
1222 
As a Pilot Study, the goal will be complete up to 20 participants in the main study to provide data 
1223 
from a variety of individuals.  This number was chosen out of feasibility and not from a formal 
1224 
power calculation.  (The pilot study for this proposal will assess ease of system use in up to 3 
1225 
individuals prior to the beginning of the main study.) 
1226 
 
1227 
 Primary Efficacy Endpoint  
1228 
The study design allows for multiple comparisons of blood glucose control during the Study 
1229 
Dinner Sessions, with for the primary comparison of interest being between the no carbohydrate 
1230 
announcement on the RocketAP (running the Meal Probability Detector and the Meal Control 
1231 
Module algorithms) compared to no carbohydrate announcement on the Control-IQ system.  Our 
1232 
primary endpoint is time-in-range 70-180 mg/dL for the 6-hour period after dinner. Additional 
1233 
comparisons are made between the RocketAP system without vs. with normal carbohydrate 
1234 
announcement (which determines efficacy vs. premeal bolus), as well as the Control-IQ system 
1235 
without vs. with carbohydrate announcement (which determines risk of missed carbohydrate 
1236 
announcement in standard of care system). 
1237 
 Secondary Outcomes 
1238 
For study period beginning after dinner and for 6h thereafter: 
1239 
• Number of hypoglycemia events  
1240 
• Time <70 mg/dL 
1241 
• Time >180 mg/dL 
1242 

CLINICAL PROTOCOL 
 
 
RocketAP_17-Nov-2020 
 
Page 55 of 61 
 
• Time >250 mg/dL 
1243 
• Units of insulin injected  
1244 
• Area under the curve when accounting for starting BG  
1245 
For study period beginning of dinner until 12 hours later: 
1246 
• Time in range 70-180 mg/dL 
1247 
• Number of hypoglycemia events  
1248 
• Time <70 mg/dL 
1249 
• Time >180 mg/dL 
1250 
• Time >250 mg/dL 
1251 
• Units of insulin injected  
1252 
• Area under the curve when accounting for starting BG  
1253 
We will also assess both safety and efficacy of the RocketAP in adolescents by assessing outcomes 
1254 
outside of the Study Dinner Sessions: 
1255 
• Time in range 70-180 mg/dL 
1256 
• Number of hypoglycemia events  
1257 
• Time <70 mg/dL 
1258 
• Time >180 mg/dL 
1259 
• Time >250 mg/dL 
1260 
• Units of insulin injected  
1261 
 
1262 
We will assess for the system’s functionality, including the ability of the system to run its code 
1263 
without error (delivering insulin safely, as planned), as well as its ability to avoid low BG <70 
1264 
mg/dL. 
1265 

CLINICAL PROTOCOL 
 
 
RocketAP_17-Nov-2020 
 
Page 56 of 61 
 
 
1266 
Baseline demographic and clinical characteristics of the cohort of all randomized participants will 
1267 
be summarized in a table using summary statistics appropriate to the distribution of each 
1268 
variable. Descriptive statistics will be displayed overall and by treatment group. 
1269 
Will include: 
1270 
• Age 
1271 
• HbA1c 
1272 
• Gender 
1273 
• Race/ethnicity 
1274 
• CGM use before enrollment 
1275 
• Diabetes duration 
1276 
• BMI 
1277 
 
1278 
The following tabulations and analyses will be performed during time on the UVa AP systems to 
1279 
assess device issues: 
1280 
• Device malfunctions requiring study team contact and other reported device issues 
1281 
• Sensor performance metrics (difference, absolute relative difference, and International 
1282 
Organization for Standardization criteria) – if applicable, by sensor version. 
1283 
• % time CGM data available - overall and by month 
1284 
• Performance metrics, describing the Closed Loop Control (CLC) system and its 
1285 
components like: 
1286 
a. % time CGM data were available to the CLC system – overall and by month 
1287 
b. % time in different operational modes per week - overall and by month  
1288 
c. Rate of different failure events and alarms per 48 hours recorded by the CLC 
1289 
system – overall and by month 
1290 

CLINICAL PROTOCOL 
 
 
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Data will not be used on any night where there is a site failure for the insulin pump and/or 
1291 
malfunction of the CGM significantly effecting BG readings. 
 
1292 

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Chapter 14  Data Collection and Monitoring 
1293 
 
1294 
The study data are collected through a combination of case report forms (electronic and paper) 
1295 
and electronic device data files obtained from the software and individual hardware 
1296 
components. These electronic device files and electronic CRFs are considered the primary source 
1297 
documentation. 
1298 
When data are directly collected in electronic case report forms, this will be considered the 
1299 
source data.  Records will be maintained in accordance with ICH E6 and institutional regulatory 
1300 
requirements for the protection of confidentiality of participants. 
1301 
 
1302 
Study documents should be retained for a minimum of 2 years after the last approval of a 
1303 
marketing application in an ICH region and until there are no pending or contemplated marketing 
1304 
applications in an ICH region or until at least 2 years have elapsed since the formal 
1305 
discontinuation of clinical development of the investigational product.  These documents should 
1306 
be retained for a longer period, however, if required by local regulations. No records will be 
1307 
destroyed without the written consent of the sponsor, if applicable. It is the responsibility of the 
1308 
sponsor to inform the investigator when these documents no longer need to be retained. 
1309 
 
1310 
A protocol deviation is any noncompliance with the clinical trial protocol, Good Clinical Practices 
1311 
(GCP), or procedure requirements.  The noncompliance may be either on the part of the 
1312 
participant, the investigator, or the study site staff. As a result of deviations, corrective actions 
1313 
may be developed by the site and implemented as appropriate.  Major deviations will be reported 
1314 
to the IRB-HSR within 7 calendar days of when the study team becomes aware of the event.  
1315 

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Chapter 15  Ethics/Protection of Human Participants 
1316 
 
1317 
The investigator will ensure that this study is conducted in full conformity with Regulations for 
1318 
the Protection of Human Participants of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 
1319 
CFR Part 56, and/or the ICH E6. 
1320 
 
1321 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
1322 
be submitted to the IRB for review and approval.  Approval of both the protocol and the consent 
1323 
form must be obtained before any participant is enrolled.  Any amendment to the protocol will 
1324 
require review and approval by the IRB before the changes are implemented to the study.  All 
1325 
changes to the consent form will be IRB approved; a determination will be made regarding 
1326 
whether previously consented participants need to be re-consented. 
1327 
 
1328 
 Consent Procedures and Documentation 
1329 
Informed consent is a process that is initiated prior to an individual’s agreement to participate in 
1330 
the study and continues throughout the individual’s study participation.  Extensive discussion of 
1331 
risks and possible benefits of participation will be provided.  Consent forms will be IRB approved 
1332 
and the participant will be asked to read and review the document.  The investigator or their 
1333 
delegate will explain the research study to the participant and answer any questions that may 
1334 
arise.  All participants will receive a verbal explanation in terms suited to their comprehension of 
1335 
the purposes, procedures, and potential risks of the study and of their rights as research 
1336 
participants.  Participant will have the opportunity to carefully review the written consent form 
1337 
and ask questions prior to signing. 
1338 
The participant and the parent(s)/legal guardians will sign the informed consent document prior 
1339 
to any procedures being done specifically for the study. The consent forms may be signed 
1340 
electronically with the use of the HIPAA compliant version of DocuSign. A copy of the informed 
1341 
consent document will be given to the participant for their records.  The rights and welfare of the 
1342 
participants will be protected by emphasizing to them that the quality of their medical care will 
1343 
not be adversely affected if they decline to participate in this study. 
1344 

CLINICAL PROTOCOL 
 
 
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 Participant and Data Confidentiality 
1345 
The study monitor, representatives of the IRB or device company supplying study product may 
1346 
inspect all documents and records required to be maintained by the investigator, including but 
1347 
not limited to, medical records (office, clinic, or hospital) for the participants in this study.   
1348 
The study participant’s contact information will be securely stored at the clinical site for internal 
1349 
use during the study.  At the end of the study, all records will continue to be kept in a secure 
1350 
location for as long a period as dictated by local IRB and Institutional regulations. 
1351 
Study participant research data, which is for purposes of statistical analysis and scientific 
1352 
reporting, will be transmitted to and stored at the University of Virginia Center for Diabetes 
1353 
Technology.  The study data entry and study management systems used by research staff will be 
1354 
secured and password protected.  At the end of the study, all study databases may be de-
1355 
identified and archived at the University of Virginia Center for Diabetes Technology. 
1356 

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Chapter 16 References  
1357 
1. Burdick J, Chase HP, Slover RH, et al. Missed insulin meal boluses and elevated 
1358 
hemoglobin A(1c) levels in children receiving insulin pump therapy. Pediatrics. 
1359 
2004;113(3):E221-E224. 
1360 
2. Olinder AL, Kernell A, Smide B. Missed bolus doses: devastating for metabolic control in 
1361 
CSII-treated adolescents with type 1 diabetes. Pediatric Diabetes. 2009;10(2):142-148. 
1362 
3. Brown SA. The International Diabetes Closed-Loop iDCL) Trial--Clinical Acceptance of the 
1363 
Artificial Pancreas. The American Diabetes Association Scientific Sessions, San Francisco, 
1364 
CA. 2019. 
1365 
4. Cherñavvsky DR, DeBoer MD, Keith-Hynes P, et al. Use of an artificial pancreas among 
1366 
adolescents for a missed snack bolus and an underestimated meal bolus. Pediatr 
1367 
Diabetes. 2016;17(1):28-35. 
1368