Safety and Feasibility Testing of a Smaller Network Version of AIDANET (MiniNET)
Phase: NA
Conditions: Type 1 Diabetes
Sponsor: Marc Breton

School of Medicine 
Center for Diabetes Technology 
Safety and Feasibility Testing of a 
Smaller Network Version of AIDANET 
Running Title: Smaller Network Pilot 
NCT06633965 
Version Number: 
v1.3 25-Oct-2024

CLINICAL PROTOCOL   
 
 
 
 
MiniNET_25-Oct-2024 
 
Page 2 of 60 
 
KEY ROLES 
 
Name, Degree 
Institution Name 
Principal Investigator, IDE 
Chair 
Marc D. Breton, PhD 
University of Virginia Center 
for Diabetes Technology  
Protocol Chair 
Sue A. Brown, MD 
University of Virginia Center 
for Diabetes Technology 
Study Physician  
Mark D. DeBoer, MD 
 
University of Virginia Center 
for Diabetes Technology  
 
 
 

CLINICAL PROTOCOL   
 
 
 
 
MiniNET_25-Oct-2024 
 
Page 3 of 60 
 
PROTOCOL VERSION HISTORY 
Version 
Number 
Author(s) 
Approver 
Effective Date 
Revision Description 
1.0 
Sue Brown 
Sue Brown,  
Mark DeBoer 
11-Sep-2024 
Original Protocol 
1.1 
Mary Oliveri 
Sue Brown,  
Mark DeBoer 
24-Sep-2024 
FDA Modifications: 
• 
Modified Glycemic 
Treatment Guidelines 
(section 7.6.1) 
• 
Modified Stopping 
Criteria (section 12.9.1) 
1.2 
Mark DeBoer 
Sue Brown,  
Mark DeBoer 
25-Sep-2024 
FDA Modifications: 
• 
Modified Glycemic 
Treatment Guidelines 
(section 7.6.1) 
 
1.3 
Mary Oliveri 
Mary Oliveri 
25-Oct-2024 
Study Team Modifications: 
• Added definition of 
AIDANET acronym 
(section 1.1) 
• Removed activity tracker 
(section 4.3) 
IRB Modifications: 
• Removed reference to assent 
(section 3.3) 
• Removed pregnancy test at 
hotel visit (section 7.3) 
 
 
 

CLINICAL PROTOCOL   
 
 
 
 
MiniNET_25-Oct-2024 
 
Page 4 of 60 
 
SITE PRINCIPAL INVESTIGATOR STATEMENT OF COMPLIANCE 
Protocol Title:  Safety and Feasibility Testing of a Smaller Network Version of AIDANET 
Running Title:  Smaller Network Pilot 
 
Protocol Version/Date: v1.3/ 25-Oct-2024 
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 
 
 

CLINICAL PROTOCOL   
 
 
 
 
MiniNET_25-Oct-2024 
 
Page 5 of 60 
 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ADA 
American Diabetes Association 
AE 
Adverse Event 
AID 
Automated insulin delivery 
AIDANET 
Automated insulin delivery as Adaptive Network 
AP 
 
Artificial pancreas 
AUC 
Area Under the Curve 
AYA 
Adolescent and Young Adult 
BDC 
Barbara Davis Center 
BG 
Blood Glucose (as assessed by a blood glucose meter) 
BGM 
Blood glucose meter 
CGM 
Continuous glucose monitor 
CSII 
Continuous subcutaneous insulin infusion 
DiAs 
Diabetes Assistant  
DKA 
Diabetic Ketoacidosis 
FCL 
Fully closed loop 
HbA1c 
Hemoglobin A1c 
HCL 
Hybrid closed loop 
JDRF 
Juvenile Diabetes Research Foundation 
MDI 
Multiple daily injections 
NAP 
Neural network artificial pancreas 
SAE 
Severe Adverse Event 
SG 
Sensor Glucose (as assessed by a continuous glucose monitor) 
SH 
Severe Hypoglycemia 
T1D 
Type 1 diabetes 
TAR 
Time above range 
TBR 
Time below range 
TIR 
Time in range 70-180 mg/dL 
 
 

CLINICAL PROTOCOL   
 
 
 
 
MiniNET_25-Oct-2024 
 
Page 6 of 60 
 
PROTOCOL SUMMARY 
Participant Area 
Description 
Title 
Safety and Feasibility Testing of a Smaller Network Version of AIDANET 
Investigational 
Device 
AIDANET algorithm as smaller network version with DiAs phone, Tandem t:AP insulin 
pumps, and Dexcom CGM 
Objectives 
The primary objective of the project is to demonstrate feasibility and safety of the 
Automated Insulin Delivery as Adaptive NETwork (AIDANET) system run in a new 
smaller network version, used in full closed loop (FCL) by adults with T1D. 
Study Design 
Randomized crossover, device safety/feasibility supervised house/hotel with transition to 
home use, interventional trial of AIDANET 
Number of Sites 
1 
Endpoint 
The primary metric for analysis will be change in mean CGM between the week of the 
control usual-care period and the one-week Remote Monitored At-Home Full Closed Loop 
period using AIDANET. 
Population 
Key Inclusion Criteria 
• 
Age 18-60 years at time of consent. 
• 
Clinical diagnosis of T1D, based on investigator assessment, of at least 1 year 
duration. 
Sample Size 
Complete 6 participants 
Treatment Groups 
Randomized Crossover: Participants will be randomized 1:1 to either conduct the control 
period before use of the AIDANET system (Group A) or after use of the AIDANET system 
(Group B). 
Participant Duration 
Approximately 3 weeks: approximately 1 week of usual care, 3 days/2 nights house/hotel 
in FCL, and 1 week At Home Remote Monitored FCL. 
Protocol 
Overview/Synopsis 
We will enroll up to 12 participants with a plan to complete 6 participants. The study will 
be performed for about 36 hours at a local hotel/rental. Following the house/hotel session, 
participants will undergo a 7 day/6-night Remote Monitored At-Home use session. We will 
also conduct a one-week control period gathering data on glycemic control and insulin 
administration with the participants usual care therapy. Participants will be randomized 1:1, 
to either Group A (control period prior to AIDANET use) or Group B (control period after 
AIDANET use).  

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 7 of 60 
 
TABLE 1. SCHEDULE OF STUDY VISITS AND PROCEDURES 
 
Screening 
Randomization 
Usual Care 
Data 
Collection 
Pre-Hotel 
Check In 
Hotel 
Admission 
with FCL 
FCL 
Equipment 
Training 
1-week 
at-home 
FCL 
Post Study 
Check-In 
Location 
CV/R/Ph 
CV/R/Ph 
Home x 1 
week 
R/Ph 
House/ 
Hotel 
House/ 
Hotel 
Home x 1 
week 
Home 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
Timeframe (days) 
1 
2 
3-10 
11 
12-14 
12 
14-21 
22 
Informed Consent 
X 
 
 
 
 
 
 
 
Eligibility 
Assessment 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
HbA1c  
X 
 
 
 
 
 
 
 
Pregnancy Test (if 
applicable) 
X 
 
 
 
 
 
 
 
Blood Testing: 
BMP, Liver 
Functioning, 
Hematocrit, TSH 
(if requested by 
MD) 
X 
 
 
 
 
 
 
 
Physical Exam 
(H&P within 6 
months permitted 
as substitute) 
X 
 
 
 
 
 
 
 
Vital Signs 
(including 
height/weight) 
(self-reported 
values permitted) 
X 
 
 
 
X 
 
 
 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 8 of 60 
 
CV = Clinic Visit; R=Remote Visit; Ph=Phone which includes text messages and emails 
Demographic Data 
Survey (if 
eligibility is met) 
X 
 
 
 
 
 
 
 
Randomization 
 
 
X 
 
 
 
 
 
 
Study Equipment 
Training 
 
 
 
 
 
X 
 
 
CGM Use 
 
 
X 
X 
X 
X 
X 
 
Fully Closed Loop 
(FCL) Use (e.g. 
AIDANET, DiAs, 
CGM) 
 
 
 
 
X 
X 
X 
 
Questionnaires  
 
 
 
 
X 
 
X 
 
Concomitant 
Medication Review 
X 
 
 
 
X 
 
 
 
Review diabetes 
management and 
AEs 
 
 
X 
X 
X 
X 
X 
X 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 9 of 60 
 
Table 2. Metric Capture Timeline 
 
Enrollment 
1-Week 
Usual Care 
Hotel  FCL 
1-Week at-
home FCL 
Visit  
1 
3 
5 
7 
Demographic Data 
x 
 
 
 
HbA1c 
x 
 
 
 
CGM Data 
 
 
 
 
Mean CGM 
 
x 
x 
x 
GMI 
 
x 
x 
x 
TIR 70-180 mg/dL 
 
x 
x 
x 
CGM StDev 
 
x 
x 
x 
CGM CV 
 
x 
x 
x 
CGM%<54 mg/dL 
 
x 
x 
x 
CGM%<70 mg/dL 
 
x 
x 
x 
CGM%>180 mg/dL 
 
x 
x 
x 
CGM%>250 mg/dL 
 
x 
x 
x 
Time in Automation 
 
 
x 
x 
Total Daily Insulin Dose 
 
x 
x 
x 
Number of Boluses per Day 
 
x 
x 
 
Exercise: CGM %<70 mg/dL 
 
 
x 
 
Unannounced Meals: 
% CGM>250 mg/dL 
 
 
x 
 
Inspire Questionnaire 
 
 
x 
x 
Technology Expectations Survey 
 
 
x 
x 
 
 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 10 of 60 
 
Table of Contents 
1 
Chapter 1: Background .............................................................................................................. 14 
2 
1.1 Introduction ......................................................................................................................... 14 
3 
1.2 Study Objective ................................................................................................................... 15 
4 
1.3 Specific Aims and Hypotheses ........................................................................................... 15 
5 
Chapter 2: Study Synopsis ......................................................................................................... 16 
6 
2.1 Study Design ....................................................................................................................... 16 
7 
2.2 Study Hardware/Software ................................................................................................... 16 
8 
2.3 Timing of Device Use ......................................................................................................... 16 
9 
2.4 Meal and Exercise Testing .................................................................................................. 17 
10 
2.5 Study Devices Download .................................................................................................... 18 
11 
2.6 Study System Issues ............................................................................................................ 18 
12 
Chapter 3: Study Screening ....................................................................................................... 19 
13 
3.1 Clinical Site ......................................................................................................................... 19 
14 
3.2 Participant Recruitment and Enrollment ............................................................................. 19 
15 
3.3 Informed Consent and Authorization Procedures ............................................................... 19 
16 
3.4 Participant Inclusion Criteria .............................................................................................. 19 
17 
3.5 Participant Exclusion Criteria ............................................................................................. 20 
18 
3.6 Screening Procedures .......................................................................................................... 21 
19 
3.7 Screen Failures .................................................................................................................... 22 
20 
3.8 Personal Equipment Downloads ......................................................................................... 23 
21 
3.9 Questionnaire ...................................................................................................................... 23 
22 
3.10 Other Considerations ........................................................................................................ 23 
23 
Chapter 4: Study Devices & Training ....................................................................................... 24 
24 
4.1 Insulin Pump ....................................................................................................................... 24 
25 
4.2 Continuous Glucose Monitor .............................................................................................. 25 
26 
4.3 Blood Glucose Meter and Strips ......................................................................................... 26 
27 
4.4 Ketone Meter and Strips ..................................................................................................... 26 
28 
4.5 Study Devices Accountability Procedures .......................................................................... 26 
29 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 11 of 60 
 
Chapter 5: Randomization ......................................................................................................... 27 
30 
Chapter 6: Usual Care Control Period ..................................................................................... 28 
31 
6.1 Usual Care Control Period .................................................................................................. 28 
32 
6.2 Pre-Hotel Check-In Visit .................................................................................................... 28 
33 
Chapter 7: Supervised Hotel Fully Closed Loop Period ......................................................... 29 
34 
7.1 Hotel Session ...................................................................................................................... 29 
35 
7.2 Qualifications and Role of the Staff.................................................................................... 29 
36 
7.3 Hotel Session Check-In....................................................................................................... 29 
37 
7.4 Study Meals ........................................................................................................................ 30 
38 
7.5 Hotel Session Activities ...................................................................................................... 30 
39 
7.6 Glycemic Treatment Guidelines ......................................................................................... 30 
40 
7.7 FCL Equipment Training .................................................................................................... 31 
41 
7.8 Hotel Session Discharge ..................................................................................................... 31 
42 
7.9 Other Issues ......................................................................................................................... 32 
43 
Chapter 8: Remote Monitored At-Home Fully Closed Loop Period ..................................... 33 
44 
8.1 At Home Participant Plan ................................................................................................... 33 
45 
8.2 Remote Monitoring ............................................................................................................. 33 
46 
8.3 Questionnaires..................................................................................................................... 33 
47 
8.4 Post-Study Check-In ........................................................................................................... 34 
48 
8.5 Early Termination Visit (If Applicable) ............................................................................. 34 
49 
8.6 Unscheduled Visits ............................................................................................................. 34 
50 
Chapter 9: Medical Monitor Safety Review ............................................................................. 35 
51 
Chapter 10: Testing Procedures ................................................................................................ 36 
52 
10.1 Laboratory and Point of Care Testing ............................................................................... 36 
53 
10.2 Questionnaires................................................................................................................... 36 
54 
Chapter 11: Risks Associated with the Clinical Trial.............................................................. 38 
55 
11.1 Potential Risks and Benefits of the Investigational Device .............................................. 38 
56 
11.2 General Considerations ..................................................................................................... 41 
57 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 12 of 60 
 
Chapter 12: Adverse Events, Device Issues, and Stopping Rules........................................... 43 
58 
12.1 Definitions......................................................................................................................... 43 
59 
12.2 Reportable Events ............................................................................................................. 44 
60 
12.3 Relationship of Adverse Event to Study Device............................................................... 45 
61 
12.4 Intensity of Adverse Event................................................................................................ 45 
62 
12.5 Coding of Adverse Events ................................................................................................ 46 
63 
12.6 Outcome of Adverse Events ............................................................................................. 46 
64 
12.7 Reportable Device Issues .................................................................................................. 47 
65 
12.8 Timing of Event Reporting ............................................................................................... 47 
66 
12.9 Stopping Criteria ............................................................................................................... 48 
67 
12.10 Independent Safety Oversight ......................................................................................... 48 
68 
12.11 Definition of a Data Breach ............................................................................................ 49 
69 
Chapter 13: Miscellaneous Considerations .............................................................................. 50 
70 
13.1 Prohibited Medications, Treatments, and Procedures ....................................................... 50 
71 
13.2 Participant Withdrawal ..................................................................................................... 50 
72 
13.3 Confidentiality .................................................................................................................. 50 
73 
13.4 Lost to Follow Up ............................................................................................................. 50 
74 
Chapter 14: Statistical Consideration ....................................................................................... 51 
75 
14.1 Design and Randomization ............................................................................................... 51 
76 
14.2 Sample Size ....................................................................................................................... 51 
77 
14.3 Outcome Measures............................................................................................................ 52 
78 
14.4 Safety Analyses ................................................................................................................. 53 
79 
14.5 Baseline Descriptive Statistics .......................................................................................... 53 
80 
14.6 Device Issues .................................................................................................................... 54 
81 
Chapter 15: Data Collection and Monitoring .......................................................................... 55 
82 
15.1 Case Report Forms and Device Data ................................................................................ 55 
83 
15.2 Study Records Retention................................................................................................... 55 
84 
15.3 Protocol Deviations ........................................................................................................... 55 
85 
Chapter 16: Ethics/Protection of Human Participants ........................................................... 56 
86 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 13 of 60 
 
16.1 Ethics Standard ................................................................................................................. 56 
87 
16.2 Institutional Review Boards .............................................................................................. 56 
88 
16.3 Informed Consent Process ................................................................................................ 56 
89 
16.4 Participant and Data Confidentiality ................................................................................. 57 
90 
Chapter 17: References .............................................................................................................. 58 
91 
 
92 
 
 
93 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 14 of 60 
 
Chapter 1: Background 
94 
 
95 
A major impediment to maintaining blood glucose (BG) control in Type 1 diabetes (T1D) is missed 
96 
meal boluses, which has been associated with significantly higher HbA1c levels.1  While the 
97 
advent of the artificial pancreas (AP) offers promise of safe reductions in HbA1c, our research 
98 
group previously found that current AP systems only partly compensate for missed prandial 
99 
insulin.2 We thus designed a new system called Automated Insulin Delivery Adaptive NETwork, 
100 
or AIDANET, to be fully automated, utilizing a Bolus Priming System (BPS) that recognizes meal 
101 
ingestion and delivers a quick priming dose of insulin prior to extreme blood sugar excursions. 
102 
When used as a fully automated closed loop (FCL) system (without any meal announcements to 
103 
the controller), this system improves glucose time-in-target range (TIR) 70-180 mg/dL compared 
104 
to a current commercially available system (Control-IQ).  We subsequently incorporated this 
105 
system in a neural net and found this to function as well as the previous model-predictive control 
106 
algorithm.  However, the long-term utility of such a system would have to be via use on an insulin 
107 
pump, requiring a refined “smaller” code set to be able to run on internal pump software.   
108 
We have thus formulated a version of AIDANET that has a smaller coding footprint.  The goal of 
109 
the current project is to assess whether this “smaller” version of AIDANET continues to provide 
110 
safe and effective glycemia management as seen in prior formulations.  The current study is a 
111 
randomized cross-over study comparing participants’ usual care with one week at home on 
112 
AIDANET. The week of control at home will follow a two-night hotel stay when participants will 
113 
be taught how to operate the new system during the at-home portion of the study. The comparator 
114 
usual care week will be randomly assigned to being before time on AIDANET (i.e., prior to the 
115 
hotel stay) or after (i.e. time after the one-week home portion).  
116 
For the majority of time on AIDANET, participants will not announce meal ingestion to the 
117 
system—using the system as an FCL system.  However, the system is designed to also be able to 
118 
be used as a hybrid system with carbohydrate announcement. Thus, as further assessment of the 
119 
system, we will instruct participants to use the system as follows: 
120 
• For one of the dinners in the hotel participants will bolus for carbohydrate content of 
121 
their meal, using their usual insulin-to-carbohydrate ratio (while the other dinner in the 
122 
hotel will be fully FCL). 
123 
• For one full day while at home participants will bolus for carbohydrates for all 
124 
ingestions (using their usual insulin-to-carbohydrate ratio). 
125 
• For another full day at home, participants will merely announce to the system each time 
126 
they begin to eat a meal or snack; this will induce the system to deliver a rapid BPS 
127 
dose (e.g. 10% of total daily insulin). 
128 
We hypothesize that performances of this smaller version of AIDANET will provide safe and 
129 
effective care when used as FCL (with the exception of the hybrid use as just described). We expect 
130 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 15 of 60 
 
that this will constitute an important step toward having an AID system that has potential to be 
131 
used embedded in insulin pumps. 
132 
 
133 
This study aims to demonstrate the safety and feasibility of the Automated insulin delivery as 
134 
Adaptive NETwork (AIDANET) system in a smaller software version, used as FCL. This study 
135 
will also assess differences in glycemia outcomes on assigned days when the participant 1) enters 
136 
total carbohydrate amount and 2) announces when food is started to be consumed. 
137 
 
138 
Aim 1: To evaluate the performance (safety, efficacy) of the smaller version of AIDANET used 
139 
as FCL. 
140 
Hypothesis: FCL use will provide as good or better mean CGM value and glucose TIR during 1 
141 
week of at-home use as compared to 1 week of standard care sensor data. 
142 
Aim 2: To evaluate the safety and efficacy of the smaller version of AIDANET during days where 
143 
participants are assigned to 1) use usual insulin-to-carbohydrate ratio and 2) use meal 
144 
announcement alone (triggering BPS). 
145 
Hypothesis: The AIDANET system will yield improved mean CGM glucose and TIR on days 
146 
when meals are announced, both using insulin-to-carbohydrate ratio and simple meal 
147 
announcement.   
 
148 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 16 of 60 
 
Chapter 2: Study Synopsis  
149 
 
150 
This study assesses adults with T1D on the AIDANET system during a 2-night house/hotel stay 
151 
and during 1 week at home (Figure 1). Participants will use the system as FCL with the exception 
152 
of using their insulin-to-carbohydrate ratio as usual during 1 dinner in the house/hotel and 1 day 
153 
at home and announcing eating initiation for 1 day at home.  We will aim to complete a total of 6 
154 
participants. We will also conduct an approximately 1-week control period gathering data on 
155 
glycemic control and insulin administration with the participants’ usual care therapy. Participants 
156 
will be randomized 1:1 to either Group A (control period prior to AIDANET use) or Group B 
157 
(control period after AIDANET use).  
158 
 
159 
• 
Figure 1: Device Use Timeline 
160 
 
161 
The study will involve testing a new AID system designed to enable full closed loop control and 
162 
consisting of the following elements: the diabetes assistant (DiAs) prototyping platform, connected 
163 
to a Tandem t:AP research insulin pump and a Dexcom G6 CGM, and implementing a new 
164 
“smaller” coding version of the University of Virginia (UVA) AIDANET algorithm. Upon arrival 
165 
at the hotel, participants will be taught how to use the Tandem t:AP pump as well as the DiAs 
166 
system, including stopping the system. 
167 
 
168 
One-Week Control Period: All participants will collect approximately one week of usual care data 
169 
to serve as control data for cross-over testing as outlined in Section 6.1. During the control period, 
170 
participants may use an insulin pump either in manual or automated mode that is capable of being 
171 
downloaded. Participants will be randomized 1:1 to either conduct the control period before use 
172 
of the AIDANET system (Group A) or after use of the AIDANET system (Group B). 
173 
Day 2
Day 1
End of
study
Group A: 1-week Usual
Care data collecƟon
Screening,
enrollment
Hotel
RandomizaƟon
Study team in contact regarding automated
hypo- and hyperglycemia alerts
Home
Day 3
All meals w/o carb
announcement except
insulin:carb use at
dinner Day 2
Group A & B: Remote Monitored At-Home Period
x 7 days/6 nights
All meals w/o carb or meal announcement, except:
One full day only meal announcement, another full
day with insulin:carbuse
Group B: 1-week Usual
Care data collecƟon
Switch to
usual care
Home
Home
Day 9
EducaƟon for
system use at home
2-night hotel stay
using AIDANET

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 17 of 60 
 
Hotel Period: Participants will arrive at the hotel prior to dinner on the afternoon of Day 1. They 
174 
will be connected to the Tandem t:AP pump, which will be connected to the DiAs platform. A 
175 
Dexcom G6 CGM may be placed on Day 1 or by the participant prior to Day 1 and will also be 
176 
connected to the DiAs platform. The system will be started in the afternoon/evening with 
177 
AIDANET enabled prior to dinner on Day 1. Participants will be taught how to use the DiAs in 
178 
this configuration. The t:AP pump will be programmed with back up parameters determined by 
179 
the study investigator(s). Once started, the participants will have their glucose values managed 
180 
through use of this system during the hotel and Remote Monitored At-Home periods. 
181 
Remote Monitored At-Home Period: Participants will continue to use the Tandem t:AP pump, 
182 
DiAs platform running the AIDANET smaller network system, and Dexcom G6 CGM for glucose 
183 
control for 7 days/6 nights during this period. At the end of the Remote Monitored At-Home 
184 
period, participants will return to their usual diabetes therapy. 
185 
 
186 
 Meal Testing  
187 
During the supervised house/hotel period, participants will be instructed to eat approximately 3 
188 
unannounced meals per full day, with the exception of using their usual insulin-to-carbohydrate 
189 
ratio with dinner one of the 2 nights. The time of completion for these meals will be recorded by 
190 
study staff. The % CGM>250 mg/dL for the 4 hours after each meal will be recorded and 
191 
specifically analyzed along with the CGM area under the curve (AUC) for the post-meal 4-hour 
192 
period. Participants will be instructed to freely eat unannounced meals during the remote-
193 
monitored at-home stage but will not be required to record the timing of the meals. The exception 
194 
is they will be instructed for 1 full day (from waking through bedtime) to announce usual insulin-
195 
to-carbohydrate for all ingestions and for another full day to announce when they begin to eat.  
196 
Participants will be educated to consume their usual diet during both the at-home control period 
197 
and the Remote Monitored At-Home FCL period. 
198 
 Exercise Testing  
199 
During the supervised hotel period, participants will engage in mild activity (a walk of 
200 
approximately 30 minutes) on Day 2. Study staff will set a Temporary Control Rate (TCR) of 
201 
approximately 50-100% starting up to approximately one hour prior to exercise for approximately 
202 
2 hours, actual TCR settings will be tailored to an individual person. Study staff will record the 
203 
duration, approximate intensity (low, moderate, or high intensity), the TBR <70 mg/dL, TBR <54 
204 
mg/dL, and any episodes of Severe Hypoglycemia (SH) during the walk and in the 2 hours after 
205 
the exercise challenges. Participants will be provided with an exercise monitor (e.g., Fitbit) for use 
206 
during the control and FCL periods. Participants will be allowed to practice their usual exercise 
207 
routine during the control and remote-monitored at-home FCL periods with use of the TCR as 
208 
needed. They will not be required to record exercise events during these periods. 
209 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 18 of 60 
 
 
210 
Data from the study devices will be captured in real-time by the remote monitoring server for the 
211 
DiAs system. In addition, study devices will be downloaded at the end of the Remote-Monitored 
212 
At-Home FCL period. 
213 
 
214 
If the CGM signal becomes unavailable for more than 20 minutes consecutively, closed loop will 
215 
not operate to automatically adjust insulin delivery. If the CGM is not connected, the system will 
216 
revert to the usual open loop function of the pump and deliver insulin with the pre-programmed 
217 
dosing parameters. Resumption of closed-loop control will occur automatically once the CGM 
218 
signal is again available. 
219 
If the DiAs system is unable to maintain connectivity with the Tandem t:AP pump, the pump will 
220 
automatically revert to the pre-programmed dosing parameters after 30 minutes without any need 
221 
for interaction from the user. 
 
222 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 19 of 60 
 
Chapter 3: Study Screening  
223 
VISIT 1 
224 
 
225 
The study will be performed at the University of Virginia. Screening procedures will be performed 
226 
either virtually or on site, at a clinical research unit, or at the hotel. 
227 
 
228 
We will enroll up to 12 participants who have been diagnosed with type 1 diabetes for at least one 
229 
year. This enrollment number accounts for dropouts or screen failures that may occur. The goal is 
230 
to complete a total of approximately 6 participants.
231 
 
232 
Before consent has been obtained, participants will be asked inclusion/exclusion criteria questions 
233 
during pre-screening to determine study eligibility. Before completing any procedures or 
234 
collecting any data that are not part of usual care, written informed consent will be obtained. 
235 
Potential eligibility may be assessed as part of routine care examination. 
236 
A participant is considered enrolled when the informed consent forms have been signed by the 
237 
participant and the study team. 
238 
Consenting procedures and documentation are defined in section 16.3. 
239 
After informed consent has been signed, a potential participant will be evaluated for study 
240 
eligibility through review of medical history, performance of physical exam by a licensed health 
241 
care professional, and other testing as needed per the I/E criteria. 
242 
 
243 
The participants must meet all of the following inclusion criteria in order to be eligible to 
244 
participate in the study. 
245 
1. Age ≥18.0 and ≤60 years old at time of consent 
246 
2. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one 
247 
year  
248 
3. Currently using insulin pump for at least three months; Any pump, either open loop or 
249 
hybrid closed loop may be used. 
250 
4. Currently using insulin for at least six months. 
251 
5. Willingness to switch to use a commercially approved personal insulin (e.g., lispro or 
252 
aspart, or biosimilar approved products) within the study pump as directed by the study 
253 
team. 
254 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 20 of 60 
 
6. Currently using a Dexcom G6 or G7 CGM. 
255 
7. Has one or more supportive companions knowledgeable about emergency procedures for 
256 
severe hypoglycemia and able to contact emergency services and study staff that either 
257 
lives with participant or located within approximately 30 minutes of participant and able 
258 
to locate participant in the event of an emergency. 
259 
8. Participant not currently known to be pregnant or breastfeeding. 
260 
9. If participant capable of becoming pregnant, must agree to use a form of contraception to 
261 
prevent pregnancy while a participant in the study (e.g. hormonal contraception, 
262 
abstinence from heterosexual intercourse). A negative serum or urine pregnancy test will 
263 
be required for all females of childbearing potential. Participants who become pregnant 
264 
will be discontinued from the study. Also, participants who during the study develop and 
265 
express the intention to become pregnant within the timespan of the study will be 
266 
discontinued. 
267 
10. Willingness to use the study FCL system (CGM, pump, and phone) during the relevant 
268 
study period. 
269 
11. Willingness not to start any new non-insulin glucose-lowering agent during the course of 
270 
the trial. 
271 
12. Willingness to participate in all study procedures including the house/hotel session, 
272 
exercise challenges (e.g., one hour per day during hotel), and to consume approximately 
273 
3 unannounced meals per day during the relevant portion of the supervised hotel session. 
274 
13. Access to internet at home and willingness to upload data during the study as needed. 
275 
14. Investigator has confidence that the participant can successfully operate all study devices 
276 
and is capable of adhering to the protocol. 
277 
15. Participant is proficient in reading and writing English. 
278 
 
279 
The participant must not have any exclusion criteria in order to be eligible to participate in the 
280 
study.  
281 
1. Plans to start a new non-insulin glucose-lowering agent (e.g., GLP-1 receptor agonists, 
282 
Symlin, DPP-4 inhibitors, sulfonylureas). Participants may be on a stable dose of such an 
283 
agent for at least the past month. 
284 
2. Current use of an SGLT-2 or SGLT-1/2 inhibitor due to risk of euglycemic DKA. 
285 
3. Hemophilia or any other bleeding disorder. 
286 
4. History of severe hypoglycemic events with seizure or loss of consciousness in the last 12 
287 
months. 
288 
5. History of DKA event in the last 12 months. 
289 
6. History of chronic renal disease (Stage 4 or unstable Stage 3b per investigator judgment) 
290 
or currently on peritoneal or hemodialysis. 
291 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 21 of 60 
 
7. History of adrenal insufficiency. 
292 
8. Currently being treated for a seizure disorder. 
293 
9. Hypothyroidism or hyperthyroidism that is not adequately treated. 
294 
10. Coronary artery disease or other heart condition that would prevent participation in 
295 
moderate intensity exercise. 
296 
11. Use of oral or injectable steroids at the time of enrollment or within the last 4 weeks. 
297 
12. Planned surgery during the study period. 
298 
13. Known ongoing adhesive intolerance that is not well managed. 
299 
14. A condition, which in the opinion of the investigator or designee, would put the 
300 
participant or study at risk. 
301 
15. Participation in another interventional trial at the time of enrollment. 
302 
16. Participant with a direct supervisor involved in the conduct of the trial. 
303 
 
304 
The participant will be evaluated for study inclusion and exclusion eligibility after the informed 
305 
consent forms have been signed by the participant and the study team. Screening procedures will 
306 
last approximately 1-2 hours. The visit may occur in-person or remotely by HIPAA compliant 
307 
video communication (e.g., Zoom, Webex) The following procedures may be performed/data 
308 
collected/eligibility criteria checked and documented: 
309 
1. Inclusion and Exclusion criteria assessed 
310 
2. Demographics, including: 
311 
a. Date of birth 
312 
b. Gender  
313 
c. Race 
314 
d. Ethnicity 
315 
3. Medical History, including diabetes history  
316 
a. Duration of disease (number of years) 
317 
b. History of pump use 
318 
c. History of CGM use 
319 
d. Current treatment 
320 
e. Severe hypoglycemia history 
321 
f. DKA history 
322 
g. History of seizures  
323 
h. Loss of consciousness 
324 
4. Basal rates or basal insulin dosing 
325 
5. Carbohydrate ratios 
326 
6. Insulin sensitivity factors 
327 
7. Target glucose 
328 
8. Average daily insulin 
329 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 22 of 60 
 
9. Surgical history 
330 
10. Allergies 
331 
11. Concomitant medications 
332 
12. Physical Examination – A historical history and physical report within 6 months of 
333 
screening appointments may be used but is not required for eligibility. If vitals are not 
334 
available, may include self-reported values of all available vitals.  
335 
a. Weight 
336 
b. Height 
337 
c. Blood pressure  
338 
d. Temperature 
339 
e. Heart Rate 
340 
13. Screening Labs 
341 
a. HbA1c point of care or laboratory; may use an HbA1c if obtained in the past month. 
342 
b. Urine or serum pregnancy test for all women of childbearing potential (this test can 
343 
be done remotely with results sent to the study team)  
344 
A physical exam documented in the prior 12 months can suffice for the physical exam but will not 
345 
serve as an exclusion criterion if not available. Participants may self-report height, weight, blood 
346 
pressure, temperature, and heart rate; or these may be obtained by study staff at the enrollment 
347 
visit. An HbA1c value obtained in the previous one month may serve for the enrollment HbA1c 
348 
value.  
349 
If needed based on medical history, investigators may include baseline chemistry panel, liver 
350 
function tests, hematocrit, and thyroid stimulating hormone (lab results within one year of 
351 
screening appointment may be used). Any labs required may be obtained at a local laboratory (e.g., 
352 
LabCorp, Quest) convenient to the participant. The study physician or physician designee will 
353 
have the discretion to repeat screening tests if applicable.  
354 
 
355 
If an exclusionary condition is identified, the study participant will be excluded from participation 
356 
with follow up and referral to their primary care physician as needed.  
357 
If the study participant is pregnant, the study physician will discuss the results of the blood test 
358 
with the participant and the participant will be asked to seek confirmation of the test and the 
359 
appropriate medical care. 
360 
361 
 
362 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 23 of 60 
 
 
363 
Up to 6 months of historical data from the participant’s personal insulin pump, glucometer, or 
364 
continuous glucose monitor may be downloaded or recorded. Data will be obtained from the 
365 
participant’s personal insulin pump, glucometer and CGM. This data may be obtained through the 
366 
commercial applications (e.g., t:connect, Tidepool, and Dexcom).  
367 
 
368 
Participants will be asked to complete the Demographic Data Survey, as described in section 9.2, 
369 
once eligibility has been met. 
370 
 
371 
This study is not meant to find out if the participant has any other disease or problem. The study 
372 
leaders will alert the participant if any of the research results are important to the participant’s 
373 
health during the study. The participant may have a copy of the screening tests to discuss with the 
374 
personal physician. If blood tests are completed, any blood left over will be thrown away. It will 
375 
not be stored for any future testing. 
 
376 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 24 of 60 
 
Chapter 4: Study Devices & Training 
377 
The study system is designed to enable full closed loop control and consisting of the following 
378 
elements: the diabetes assistant (DiAs) prototyping platform (smart phone), connected to a Tandem 
379 
t:AP research insulin pump and a Dexcom G6 CGM, and implementing a new “smaller” coding 
380 
version of the University of Virginia (UVA) AIDANET algorithm. 
381 
 
382 
 Equipment Description. 
383 
A study insulin pump will be provided to all participants at the training session. The participants 
384 
will be trained in the basic functionality (e.g., bolus menu and infusion set change menu) for the 
385 
study pump. For the Tandem pumps a training checklist is available on-line with relevant sections 
386 
applicable to the study pump will be covered. 
387 
The  t:AP research CSII pump will be programmed with the participants' usual pump parameters 
388 
(basal insulin rate, insulin to carbohydrate ratio, and insulin correction factor) as determined by 
389 
the study physician at the onset of the hotel phase. These parameters serve as backup-only settings 
390 
for the system in open loop mode, and do not determine behavior of the AIDANET algorithm. The 
391 
bolus priming system (BPS) profile determines the maximum fraction of total daily insulin (TDI) 
392 
that can be injected by the BPS depending on the time of day (e.g., 8% between 06:00 and 10:00). 
393 
The BPS profile is a setting on DiAs which can be modified by the provider to impact performance 
394 
of the AIDANET algorithm. The study physician may alter the BPS profile during the hotel and 
395 
at-home portions of the study to optimize participant safety with the experimental system. 
396 
 Equipment Training 
397 
Training on the DiAs and study pump may begin at the hotel after the AIDANET system has been 
398 
put in place. The purpose of this training is to introduce the study system to the participant. Insulin 
399 
parameters will be determined by the investigator(s) and programmed into their study insulin pump 
400 
and confirmed by two research staff. Participants will then switch to the study insulin pump. The 
401 
participant’s personal pump will be removed. The investigator may elect to use an existing 
402 
personal pump infusion site at their discretion at the start of the study. The participant will be 
403 
instructed on charging the pump, menu navigation, bolus procedures, and infusion site changes. 
404 
Data-driven optimization of pump settings can occur at any time prior to the hotel session, 
405 
particularly if the participant contacts the study physician due to concerns about their pump 
406 
settings due to recurring hypo- or hyperglycemia. During closed loop testing, study investigators 
407 
may change pump settings as needed to optimize participant safety with the experimental system. 
408 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 25 of 60 
 
 
409 
 Equipment Description 
410 
The study CGM will include the Dexcom G6 transmitter and sensor. Participants may elect to wear 
411 
their personal Dexcom G6 CGM equipment throughout the study period. If currently wear a G7 
412 
CGM model, the participant will be provided with G6 CGM supplies. These sensors may be worn 
413 
for up to 10 days of continuous wear. The G6 transmitter may be worn for 3 months.  
414 
 CGM Training 
415 
A study CGM will be provided to all participants at the training session which is expected to occur 
416 
prior to the hotel session or prior to the usual care period based on the current use of CGM and 
417 
randomization. Participants using the Dexcom G6 may continue their personal CGM during the 
418 
study session. The participants will be provided with CGM equipment and instructed to use CGM 
419 
on a daily basis. If the participant has prior use of the G6, retraining will be specific to the 
420 
individual. The study team may elect to have less frequent CGM users watch the Dexcom online 
421 
training videos (https://www.dexcom.com/training-videos) to assist in the training session. Study 
422 
staff training may include review of the study CGM in real-time to make management decisions 
423 
and how to review the data after an upload for retrospective review. Study staff will specifically 
424 
identify how alarms are set using the app and the frequency that these alarms will repeat. 
425 
For participants not using the Dexcom G6, the participants will be observed placing the sensor and 
426 
will learn/review how to access the CGM trace via the Dexcom G6 commercial app (prior to the 
427 
hotel session) and via the DiAs phone (during the hotel session). The participants will be asked to 
428 
perform fingerstick blood glucose measurements (if needed) in accordance with the labelling of 
429 
the study CGM device. An electronic copy of the CGM user’s guide will be provided for these 
430 
participants to read. The study team will be sure that the participants will leave the training session 
431 
knowing how to properly use the CGM. The study team will be available for any questions. 
432 
The study team will ask participants to share their data to the study Dexcom clinical account. This 
433 
requires a one-time confirmation of data sharing between either the participant’s personal Dexcom 
434 
account or the study Dexcom account and the study clinical account. Participants are identified in 
435 
the study clinical account by their assigned participant number. The participant does not need to 
436 
provide the study team with their own login information at any point in this process. The Dexcom 
437 
clinical account allows the study team to remotely assess and download data as needed. Data 
438 
sharing between the personal Dexcom account or study Dexcom account and the clinical account 
439 
can be ended at any time by the participant. 
440 
During Usual Care phase, participants will have the option of using their personal smartphone or 
441 
receive a study smartphone to use in order to collect the data from the devices. They may also use 
442 
their own Dexcom G6 or G7 CGM.  If the participant elects to use a personal device, the Dexcom 
443 
app will be downloaded to their phone in order to monitor the participant’s CGM values and alerts 
444 
in real-time may be used prior to initiating DiAs. 
445 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 26 of 60 
 
 
446 
 Equipment Description 
447 
A study glucometer will be provided to all participants to wear during the entire study to record 
448 
any blood glucose levels measured during the study.  
449 
 Equipment Training 
450 
Participants will be advised to use the study glucometer when experiencing a low or high glucose 
451 
values as defined in the Glycemic Treatment Guidelines. The Dexcom CGM will be calibrated, if 
452 
needed, using the study glucometer and test strips in accordance with the manufacturer’s labeling.  
453 
If the study glucometer provides an app, the study team will  request that the app be downloaded 
454 
to the participant’s personal phone. The app will permit continued visibility of blood glucose 
455 
values to the participant and permit the study team to download the data without returning the 
456 
glucometer at the end of the study.  
457 
 
458 
Blood ketone levels will be measured during the hotel and at-home portions of the study with 
459 
either the Abbott Precision Xtra Meter or the Ketomojo Meters and ketone test strips in accordance 
460 
with the manufacturer’s labeling. Urine ketone strips may be provided to the participant for the at-
461 
home data collection period. The glucometer component of either ketone meters will not be used. 
462 
 
463 
Device serial numbers will be recorded, and use of equipment will be tracked. 
464 
465 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 27 of 60 
 
Chapter 5: Randomization  
466 
VISIT 2 
467 
Once eligibility is met and screening procedures are completed, the participant will proceed to 
468 
Randomization. Participants will be randomized 1:1 to assess a 1-week usual care period before use of 
469 
the AIDANET system (Group A) or after use of the AIDANET system (Group B).   
470 
Participants who screen-fail or dropout will be replaced if it occurs prior to the Hotel Admission. 
471 
Randomization will occur via REDCap module. 
472 
GROUP A: Participants will complete one week at home usual care before the use of the 
473 
AIDANET system at the hotel admission. 
474 
GROUP B: Participants will complete one week at home usual care after the use of the AIDANET 
475 
system at the hotel admission. 
 
476 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 28 of 60 
 
Chapter 6: Usual Care Control Period 
477 
 
478 
VISIT 3 
479 
During the usual-care control period, participants will continue to use their personal insulin pump 
480 
in either manual or automated mode. The mode selected must be capable of downloading the data 
481 
and sharing it with the study team. Participants using Dexcom CGM will continue to use their 
482 
personal CGM or the study CGM and will share their CGM download data with the study team at 
483 
the completion of the Usual Care period.  
484 
All participants will be provided with a study glucometer to collect blood glucose values during 
485 
the study. This study team will download this glucometer at the conclusion of the study. 
486 
Participants will be instructed to follow their normal routine involving diet, exercise, and insulin 
487 
administration. 
488 
Any relevant contacts will be recorded on the CRF and summarized as appropriate (e.g. contact 
489 
that is not a scheduling or supplies issue will not be recorded).  
490 
 
491 
VISIT 4 
492 
All participants will be contacted by the study team approximately 24-48 hours prior to the hotel 
493 
admission. The study team will verify the following information: 
494 
a. Inquire about any changes to the participant’s medical history 
495 
b. Study equipment (e.g., CGM) has been initiated. A new CGM sensor will be placed 
496 
approximately 24-72 hours prior to the hotel session for proper warm-up. 
497 
c. Verify with participant that the goal CGM reading at time of arrival is less than 200 
498 
mg/dL; this may require contact with the study physician prior to arrival on the day 
499 
of the study visit.  
500 
d. Participants will be encouraged to complete the INSPIRE and Technology 
501 
Acceptance surveys prior to the hotel admission but no later than the initiation of the 
502 
study equipment at the hotel admission.  
503 
Should any concerns regarding medical history, pump information, or unforeseen issues arise, the 
504 
admission will be cancelled for that participant at the discretion of the investigator. 
505 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 29 of 60 
 
Chapter 7: Supervised Hotel Fully Closed Loop Period 
506 
VISIT 5 
507 
 
508 
The study will be performed for about 36 hours at a local hotel/rental. Participants will use the 
509 
AIDANET system in the hotel setting from the afternoon/evening of Day 1 through discharge in 
510 
the morning of Day 3. They will then continue to use the system for the at-home period of the 
511 
study. 
512 
 
513 
There will be at least two study staff present at all times at the study site, at least one of whom will 
514 
be clinical staff (e.g., nurse, physician, nurse practitioner, physician assistant). There will be a 
515 
physician at the hotel or nearby on call during the study at all times. In addition, at least one senior 
516 
engineer will be on call during the entire hotel session. Participants will be remotely monitored by 
517 
at least one study team member (maybe trained staff, nurse, physician, NP, or PA) using a web-
518 
based remote monitoring system that has been previously established for DiAs. The web-based 
519 
remote monitoring system will display real-time insulin delivery, CGM and other system 
520 
information to allow for patient safety monitoring. In addition, study team members will be trained 
521 
in all protocol and Glycemic Treatment Guideline procedures. The closed-loop system will be 
522 
managed by the participant with study-staff supervision, particularly at the time of insulin boluses 
523 
(if needed). Glucagon for the emergency treatment of hypoglycemia will be available on-site. 
524 
Participants will be instructed to bring their own rescue glucagon, though each site will also bring 
525 
emergency rescue glucagon to the study. 
526 
 
527 
Participants will arrive at the hotel on the first day of the hotel session. The study team will perform 
528 
vital signs and inquire about any changes to the participant’s medical history. Any changes to 
529 
medical history will be communicated to the medical physician to ensure continued eligibility and 
530 
participation.   
531 
The participant ’s CGM reading, and ketone concentration will be recorded. In the event that the 
532 
participant’s CGM reading is not between 80-250 mg/dL or ketone concentration is ≥0.6 mmol/L 
533 
prior to initiation of the FCL system, the study physician may recommend additional insulin dosing 
534 
according to the participants’ usual doses. Study physician may elect to cancel participant’s 
535 
participation in the hotel admission if concerned about their medical safety. This participant will 
536 
not be replaced.  
537 
The participant’s home insulin pump will be discontinued, and the study insulin pump will be 
538 
initiated.  The study team will ensure the proper function of the CGM and insulin pump. The CGM 
539 
used in the study is FDA-approved for the non-adjunctive measurement of blood glucose (i.e., the 
540 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 30 of 60 
 
CGM reading can be used for insulin dosing decisions). The CGM readings will be the primary 
541 
source of blood glucose values. There is no required protocol fingerstick blood glucose 
542 
measurements other than at times of CGM calibration (if necessary) and if directed by the study 
543 
team. Fingerstick blood glucose measurements may be taken whenever participants experience 
544 
symptoms, if the CGM glucose is suspected to be erroneous, or any time the participant would like 
545 
to be reassured. Glycemic Treatment Guidelines to be used during the hotel admission are defined 
546 
in section 7.6.  
547 
 
548 
Participants will eat approximately 3 freely chosen unannounced meals per day during the 
549 
supervised hotel session. Study staff will record the time the meal was eaten so that analysis of the 
550 
AIDANET algorithm’s performance around the mealtime may be conducted. Participants will use 
551 
their usual insulin:carbohydrate ratio at dinner on Day 2. No other meal announcement will occur 
552 
during the hotel stay. Snacks with carbohydrates will not be allowed unless for the treatment of 
553 
low blood sugars. Non-carbohydrate snacks may be allowed throughout the hotel session per 
554 
investigator discretion. Blood glucose levels will be followed via CGM with interventions for 
555 
glucose extremes as per the Glycemic Treatment Guidelines. 
556 
 
557 
Participants will engage in a walk of approximately 30 minutes on Day 2 of the hotel stay. 
558 
Participants must have a CGM value of at least 80 mg/dL in order to begin the walk. The timing 
559 
of exercise will be recorded by study staff so that analysis of the AIDANET algorithm’s 
560 
performance around exercise may be conducted. Participants will already be wearing an exercise 
561 
monitor as part of the study protocol. 
562 
The walk will be terminated early with subjective symptoms such as shortness of breath, chest 
563 
pain, dizziness, palpitations, or any such concerning symptoms reported by participants. 
564 
Participants will stop their participation in the exercise portion of the study if reporting any 
565 
concerning symptoms. Study physicians (or physician’s assistants) will assess the participants for 
566 
their need for additional care outside the study. If symptoms resolve entirely and there is no 
567 
additional requirement for care outside the study, participants may then continue with the 
568 
remainder of the study per investigator discretion.  
569 
Participants will also be free to engage in additional low-intensity activity (i.e., walking) during 
570 
the hotel admission. Study staff will accompany participants if they leave the house/hotel.  
571 
 
572 
Hypo- and Hyperglycemia occurring while using the AIDANET system will be managed per the 
573 
following protocol during both the hotel and at-home portions of the trial. Glycemic Treatment 
574 
Guidelines will be available for staff use during the study sessions and will be provided to 
575 
participants for the at-home phase of the study. 
576 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 31 of 60 
 
 Hypoglycemia 
577 
a. If CGM falls below 70 mg/dL at any time, confirm <70mg/dL CGM readings and 
578 
potential hypoglycemia symptoms with a fingerstick blood glucose. If blood glucose 
579 
confirms <70mg/dL CGM reading, hypoglycemia will be treated with oral glucose 
580 
of approximately 5-15 g. Participants will be encouraged to wait 15 min prior to 
581 
giving a second glucose treatment.  These fingerstick checks will be performed 
582 
during the hotel stay and during the home portion if the participant chooses to do so.  
583 
During the hotel stay we will also recheck a fingerstick blood glucose before 
584 
retreatment.   
585 
b. If a participant experiences any symptoms of hypoglycemia (e.g., shakiness, 
586 
dizziness, sweating, pallor, clumsiness, difficulty paying attention, or tingling 
587 
around the mouth), then the participant should treat with oral glucose of 5-15 g. 
588 
Participants will be encouraged to wait 15 min prior to giving a second glucose 
589 
treatment.  During the hotel portion of the study, a fingerstick blood glucose will be 
590 
assessed before such treatment for symptoms and before any re-treatment. 
591 
c. If a participant displays any signs of neuroglycopenia (e.g., lethargy, disorientation, 
592 
confusion, or inappropriate behavior) or severe hypoglycemia (e.g., hypoglycemic 
593 
seizure, loss of consciousness, inability to properly consume treatment) 
594 
hypoglycemia will be treated with either oral glucose or glucagon. The patient will 
595 
be discharged from the study. The participant should consult with a study physician 
596 
to discuss next steps for broader evaluation of symptoms unrelated to hypoglycemia. 
597 
 Hyperglycemia 
598 
If CGM value is >300 mg/dL for 2 hours or >400 mg/dL at any time, check fingerstick BG and 
599 
ketone level every 60±15 minutes. If unexplained hyperglycemia, evaluate the integrity of the 
600 
insulin site, consider changing the site and providing a correction bolus as recommended by the 
601 
bolus calculator. If insulin is given subcutaneous injection rather than through the DiAs, closed-
602 
loop control should be suspended for up to four hours unless directed by a study clinician. 
603 
 
604 
VISIT 6 
605 
Participants will receive training on at-home use of the study system, safety protocols, and at-home 
606 
study contacts on the day of discharge. Study equipment training is described in section Chapter 
607 
4:.  
608 
 
609 
Discharge will occur after breakfast on Day 3. After discharge, participants will proceed to the 
610 
Remote Monitored At-Home Phase of the study. 
611 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 32 of 60 
 
 
612 
The participant will be instructed to notify study staff if they experience any issues with the study 
613 
devices. During the hotel phase, staff will provide hands-on support and troubleshooting training 
614 
for any device issues. If subcutaneous insulin is needed, the participant will turn off closed-loop 
615 
mode as instructed by study staff. During the at-home phase, participants will be instructed to 
616 
contact the staff on-call in the event of subcutaneous insulin need. If insulin is delivered by any 
617 
means other than the study pump, the participant will be instructed to turn off closed-loop mode 
618 
for approximately four hours. This timeframe can be adjusted  by the study physician. 
619 
The participant will also be asked to alert the study clinical staff for technical issues with the 
620 
Tandem research pump and/or the DiAs system, including use of the study pump and study CGM 
621 
(open loop mode) during periods of component disconnections or technical difficulties.  
622 
Glucagon will be available at the hotel once the investigational system is in place. All participants 
623 
will confirm that they have rescue glucagon available at home for the at-home phase. 
624 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 33 of 60 
 
Chapter 8:  Remote Monitored At-Home Fully Closed Loop Period 
625 
VISIT 7 
626 
 
627 
Upon discharge on day 3 of the hotel period, participants will begin a 7 day/6-night Remote 
628 
Monitored At-Home stage of the study. Participants will continue to wear the FCL research system 
629 
as initiated during the hotel period. Participants will be instructed to eat approximately 3 freely 
630 
chosen meals per day without announcing them to the system. The exception is that on 2 separate 
631 
days participants will 1) announce all food intake (triggering an immediate BPS dose) and 2) use 
632 
their usual insulin-to-carbohydrate ratio for all food ingestion. Participants will be instructed to 
633 
participate in their usual level of physical activity. Participants will complete the study after lunch 
634 
on overall study day 9 (Day 7 of the home portion), at which point they will return to use of their 
635 
usual diabetes care.  
636 
Participants in Group A will complete the study after this 1-week FCL data collection period. 
637 
Participants in Group B will then begin the Usual Care control period for data comparison (see 
638 
section 6.1). 
639 
 
640 
All participants will continue to be remote monitored during the At-Home period of the study 
641 
using the connection between DiAs and Diabetes Web Monitoring (DWM) platform at UVA. 
642 
Study staff may review the AID system data on the DWM platform as needed; in addition, at each 
643 
site, a licensed medical provider (MD, PA, NP, RN, CDCES) will receive the following automated 
644 
alerts from the DWM (automated notification system, ANS): 
645 
1. CGM > 300 mg/dL for 1 hour. 
646 
2. CGM < 70 mg/dL for 20 minutes. 
647 
3. CGM < 55 mg/dL at any point. 
648 
4. No sensor data for > 1 hour. 
649 
The provider on call will contact study participants (e.g., call, text, or video chat) and/or their 
650 
companion for any of the above CGM alerts which are not resolved within a timely manner. 
651 
Participants will be asked to manage glycemic extremes per the hyper- hypoglycemia safety 
652 
protocol. 
653 
Contact (e.g., phone, text, email, etc.) with the study team will occur as needed. Any relevant 
654 
contacts will be recorded on the CRF and summarized as appropriate (e.g. contact that is not a 
655 
scheduling or supplies issue will not be recorded).  
656 
 
657 
All participants will complete the INSPIRE and Technology Acceptance survey: 
658 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 34 of 60 
 
• Prior to initiating the study equipment at the hotel admission 
659 
• At the conclusion of the one week of At-Home FCL data collection.  
660 
 
661 
VISIT 8 
662 
Approximately 24-48 hours after the hotel session, the study team will contact the participant via 
663 
phone/email/text/video to:  
664 
• Ask about any changes to the participant’s medical history and medication. 
665 
• Review any hypoglycemic events that are less than 60 mg/dL. 
666 
• Review any hyperglycemic events that are more than 300 mg/dL . 
667 
• Verify that questions have been answered. The study physician or designee will be 
668 
available for any questions related to insulin adjustments/parameters. 
669 
The study team may contact the participant for issues related to data collection and equipment 
670 
issues.  
671 
 
672 
Participants will be asked to attend the Post-Study Check-In Visit (visit 8) in the event of a 
673 
withdrawal or early termination.  
674 
 
675 
Participants may have unscheduled visits during the study period if required for additional device 
676 
training or other unanticipated needs per the study investigator discretion.  
 
677 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 35 of 60 
 
Chapter 9:  Medical Monitor Safety Review 
678 
The Medical Monitor will review compiled safety data at the conclusion of the trial. In addition, 
679 
the Medical Monitor will review all DKA and severe hypoglycemia irrespective of relatedness to 
680 
study device use, and all serious events (including UADEs) related to study device use at the time 
681 
of occurrence. The Medical Monitor also will be informed of any Adverse Device Effects (ADE) 
682 
not meeting criteria for a UADE if the Study PI requests the Medical Monitor review. The Medical 
683 
Monitor can request modifications to the study protocol or suspension or stoppage of the study if 
684 
deemed necessary based on the totality of safety data available. 
 
685 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 36 of 60 
 
Chapter 10:  Testing Procedures 
686 
 
687 
 HbA1c  
688 
A blood sample (either capillary or venous draw) will be obtained at screening to obtain a baseline 
689 
Hemoglobin A1c level. A blood test obtained within 4 weeks prior to enrollment may be used. 
690 
HbA1c level may be measured by the study team using the DCA2000, a comparable point of care 
691 
device, at time of screening. Labs may be obtained at a local laboratory (e.g., LabCorp, Quest) 
692 
convenient to the participant. 
693 
 Pregnancy Test 
694 
A serum or urine pregnancy test will be required for women of childbearing potential at in person 
695 
visit and admission. Test must be negative to participate in the study. 
696 
 
697 
 Demographic Data Survey 
698 
Research in diabetes technology has revealed significant disparities in minoritized population’s 
699 
representation in clinical trials and access to devices that improve diabetes outcomes. Collection 
700 
of detailed demographic data regarding participants in technology trials has become essential. This 
701 
includes data on race/ethnicity, income levels and insurance status, as well as education and other 
702 
variables that describe the study population.  
703 
The Demographic Data Survey will be electronically administered once eligibility has been met. 
704 
The below information will be gathered for all participants. 
705 
a. Age 
706 
b. Gender 
707 
c. Race 
708 
d. Ethnicity 
709 
e. Martial status 
710 
f. Level of education 
711 
g. Employment status 
712 
h. Household income 
713 
i. Health insurance status 
714 
j. Monthly insulin costs and co-payments 
715 
  INSPIRE Questionnaire 
716 
The self-administered INSPIRE (INsulin Dosing Systems: Perceptions, Ideas, Reflections and 
717 
Expectations) questionnaires have been developed to determine the psychosocial impact of AID 
718 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 37 of 60 
 
systems in a range of relevant factors specific to youth with T1D (8-17 years of age) and adults 
719 
with T1D, as well as parents/caregivers of youth with T1D, and partners of adults with T1D.  
720 
The questionnaire will be administered at the onset of hotel admission and at the conclusion of the 
721 
study.  
722 
 Technology Expectations Survey  
723 
Participants will complete a Technology Expectation/Acceptance Survey which includes questions 
724 
about attitudes, feelings, and behaviors related to the technology used in this study. AID Benefits 
725 
and Burdens Scale Survey  
726 
The questionnaire will be administered prior to or at the onset of hotel admission and at the 
727 
conclusion of the study.  
 
728 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 38 of 60 
 
Chapter 11: Risks Associated with the Clinical Trial 
729 
 
730 
Risks and Benefits are detailed below. Loss of confidentiality is a potential risk; however, data are 
731 
handled to minimize this risk.  Hypoglycemia, hyperglycemia and ketone formation are always a 
732 
risk in participants with type 1 diabetes and participants will be monitored for these symptoms.  
733 
 Venipuncture Risks 
734 
A hollow needle/plastic tube will be placed in the arm for taking blood samples. Blood draws can 
735 
cause some common reactions like pain, bruising, or redness at the sampling site. Less common 
736 
reactions include bleeding from the sampling site, formation of a small blood clot or swelling of 
737 
the vein and surrounding tissues, and fainting. 
738 
 Fingerstick Risks 
739 
About 1 drop of blood will be removed by fingerstick for measuring blood sugars and sometimes 
740 
HbA1c or other tests. This is a standard method used to obtain blood for routine hospital laboratory 
741 
tests.  Pain is common at the time of lancing.  In about 1 in 10 cases, a small amount of bleeding 
742 
under the skin will produce a bruise. A small scar may persist for several weeks.  The risk of local 
743 
infection is less than 1 in 1000. This should not be a significant contributor to risks in this study 
744 
as finger sticks are part of the usual care for people with diabetes. 
745 
 Subcutaneous Catheter Risks (CGM) 
746 
Participants using the CGM will be at minimal risk for developing a local skin infection at the site 
747 
of the sensor needle placement.  If a needle is left under the skin for more than 24 hours, it is 
748 
possible to get an infection where it goes into the skin, with swelling, redness and pain. There may 
749 
be bleeding where the catheter is put in and bleeding under the skin causes a bruise (1 in 10 risk). 
750 
Study staff should verbally alert the participant that on rare occasions, the CGM may break and 
751 
leave a small portion of the sensor under the skin that may cause redness, swelling, or pain at the 
752 
insertion site. The participant should be further instructed to notify the study coordinator 
753 
immediately if this occurs. 
754 
 Risks of Hypoglycemia  
755 
As with any person having type 1 diabetes and using insulin, there is always a risk of having low 
756 
blood sugar (hypoglycemia). The frequency of hypoglycemia should be no more and possibly less 
757 
than it would be as part of daily living. Symptoms of hypoglycemia can include sweating, 
758 
jitteriness, and not feeling well. Just as at home, there is the possibility of fainting or seizures 
759 
(convulsions) and that for a few days the participant may not be as aware of symptoms of 
760 
hypoglycemia. A CGM functioning poorly and significantly over-reading glucose values could 
761 
lead to inappropriate insulin delivery. 
762 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 39 of 60 
 
 Risks of Hyperglycemia  
763 
Hyperglycemia and ketonemia could occur if insulin delivery is attenuated or suspended for an 
764 
extended period or if the pump or infusion set is not working properly. A CGM functioning poorly 
765 
and significantly under-reading glucose values could lead to inappropriate suspension of insulin 
766 
delivery. 
767 
 Risks of Device Reuse  
768 
Participant will be informed that FDA or relevant national authorities have approved the insulin 
769 
pump, CGM, glucometer and ketone meter for individual use and that by using them among 
770 
multiple patients, bloodborne pathogens (i.e. Hepatitis B) may be spread through the use of 
771 
multiple users. 
772 
The study CGM system is labelled for single patient use only. The sensor (the component of the 
773 
system that enters the skin) will be individual use only. The transmitter and receiver may be reused 
774 
during the study after the study team cleans the device using a hospital-approved cleaning 
775 
procedure. The transmitter is attached to the sensor but does not enter the skin and the receiver, if 
776 
used, is a handheld device.  
777 
CGM cleaning instructions are provided in the Dexcom G4 Platinum (Professional) Cleaning and 
778 
Disinfection manual (current edition) and a similar approach will be applied for the CGMs used in 
779 
this study. 
780 
The study insulin pumps are labelled for single patient use. During the study, this device may be 
781 
reused after the study team cleans the device with a hospital-approved cleaning procedure. All 
782 
infusion set equipment will be single patient use only (infusion set insertion kits, tubing, cartridges 
783 
etc.)   
784 
The study-provided blood glucose meter will be returned to the study participant at the conclusion 
785 
of the study after the study team has confirmed data collection. The study team will use cleaning 
786 
procedures if it is necessary to be in physical contact with the equipment to download the device. 
787 
The study team will clean the ketone meter per manufacturer directions.  
788 
 Device Cleaning Instructions 
789 
Members of the study team will clean the study equipment after use as noted in these instructions. 
790 
CGM cleaning instructions are provided in the Dexcom G4 PLATINUM (Professional) Cleaning 
791 
and Disinfection manual (current edition). The transmitter should be cleaned with Clorox 
792 
Healthcare® Bleach Germicidal Cleaner or any disinfectant product in a spray bottle containing a 
793 
bleach solution of 6500 parts per million with the EPA registration number 56392-7. The 
794 
transmitter will be submerged in this solution and then placed on an absorbent wipe or clean 
795 
surface. Two sprays will be dispensed from the Clorox cleaner onto each side of the transmitter. 
796 
A nylon brush will be used to scrub the transmitter on all sides for 30 seconds.  The transmitter 
797 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 40 of 60 
 
will be placed in the Clorox Cleaner solution for one minute. The transmitter is then rinsed under 
798 
flowing tap water for ten seconds. The transmitter will then be disinfected using a disinfectant 
799 
product with EPA registration number 56392-7 using similar procedures as the cleaning process.   
800 
Per the pump manufacturer, the insulin pump will be cleaned with a damp lint-free cloth. Use of 
801 
household or industrial cleaners, solvents, bleach, scouring pads, chemicals, or sharp instruments 
802 
are prohibited. The pump should never be submerged in water. If needed, use only a very mild 
803 
detergent, such as a bit of liquid soap with warm water. A soft towel will be used to dry the pump.  
804 
The glucometer is cleaned and disinfected with two separate Super Sani-Cloths (EPA number 
805 
9480-4). The entire surface will be cleaned, making sure the surface stays wet for 2 minutes. This 
806 
step is repeated with a clean cloth for disinfecting the device.  
807 
The Precision Xtra User’s Guide suggests that healthcare professionals use 10% bleach, 70% 
808 
alcohol or 10% ammonia to clean the device.  
809 
Equipment that touches intact skin will be cleaned with ethyl or isopropyl alcohol (70-90%), 
810 
quaternary ammonium germicidal detergent (i.e. Cavicide, EPA number 46781) or household 
811 
bleach. The contact time on the surface depends on the method used to clean the equipment. 
812 
Cavicide requires three minutes on the surface of the equipment. Clorox Germicidal Bleach Wipes 
813 
require two minutes on the equipment. The surface should remain wet (i.e. slightly damp) with the 
814 
disinfectant to be considered effective though not wet enough to leave drops of liquid.  
815 
In the event a manufacturer updates cleaning procedures for their device, the study team will 
816 
adhere to the most current recommendations.  
817 
There is the risk of blood sampling collection and contamination from sampling techniques. Hand 
818 
washing with either soap & water or waterless hand sanitizer will be used prior to caring for the 
819 
study subject. Gloves will be worn during blood sample collection and processing. Medical 
820 
personnel will continue to practice hygiene for the subject’s protection (i.e. hand washing, 
821 
changing gloves frequently, disposing needles properly). Gloves will be removed, and hands 
822 
washed or sanitized prior to leaving and upon return to the subject’s room. Soiled linen will be 
823 
changed to minimize the transfer of pathogenic organisms. 
824 
 Hb1Ac Risk 
825 
An NGSP Point of Care analyzer (i.e. DCA Vantage Analyzer) will be utilized at the research site 
826 
to obtain the subject’s HbA1c level. 
827 
 Other Risks  
828 
Some participants may develop skin irritation or allergic reactions to the adhesives used to secure 
829 
the CGM, or to secure the insulin infusion sets for the continuous subcutaneous insulin infusion.  
830 
If these reactions occur, different adhesives or “under-taping” (such as with IV 3000, Tegaderm, 
831 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 41 of 60 
 
etc.) will be tried, sites will be rotated frequently, and a mild topical steroid cream or other 
832 
medication may be required. 
833 
Whenever the skin is broken there is the possibility of an infection. The CGM and pump infusion 
834 
sites are inserted under the skin. It is possible that any part that is inserted under the skin may cause 
835 
an infection. These occur very infrequently, but, if an infection was to occur, oral and/or topical 
836 
antibiotics can be used. The risk of skin problems could be greater if you use a sensor for longer 
837 
than it is supposed to be used. Therefore, participants will be carefully instructed about proper use 
838 
of the sensor. 
839 
Data downloaded from the CGM, insulin pump, glucometer, and ketone meter will be collected 
840 
for the study as measures of diabetes self-management behaviors. Some people 
841 
may be uncomfortable with the researchers' having such detailed information about their daily 
842 
diabetes habits. 
843 
 Known Potential Benefits  
844 
It is anticipated that this protocol will yield increased knowledge about using an automated 
845 
closed-loop system with anticipatory action to control glucose levels. The individual participant 
846 
may not benefit from study participation. 
847 
 Risk Assessment 
848 
Based on the facts that (1) adults and adolescents with diabetes experience mild hypoglycemia and 
849 
hyperglycemia frequently as a consequence of the disease and its management, (2) the study 
850 
intervention involves periodic automated insulin dosing that may increase the likelihood of 
851 
hypoglycemia, and periodic automated attenuation of insulin delivery that may increase the 
852 
likelihood of hyperglycemia, (3) mitigations are in place, and have been tested in prior studies 
853 
using the investigational device system in the home setting, that limit the likelihood of excessive 
854 
insulin dosing or prolonged withdrawal of insulin, and (4) rapid reversal of hypoglycemia and 
855 
hyperglycemia can be achieved, it is the assessment of the investigators that this protocol falls 
856 
under DHHS 46.405 which is a minor increase over minimal risk. In addition, it is the belief of the 
857 
investigators that this study also presents prospects of direct benefit to the participants and general 
858 
benefit to others with diabetes. 
859 
 
860 
The study is being conducted in compliance with the policies described in the study policies 
861 
document, with the ethical principles that have their origin in the Declaration of Helsinki, with the 
862 
protocol described herein, and with the standards of Good Clinical Practice (GCP). 
863 
Whenever possible, data will be directly collected in electronic case report forms, which will be 
864 
considered the source data. 
865 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 42 of 60 
 
The protocol is considered a significant risk device study, due to the fact that the closed loop 
866 
system is experimental. Therefore, an investigational device exemption (IDE) from the U.S. Food 
867 
and Drug Administration (FDA) is required to conduct the study. 
 
868 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 43 of 60 
 
Chapter 12: Adverse Events, Device Issues, and Stopping Rules 
869 
 
870 
 Adverse Events (AE) 
871 
Any untoward medical occurrence in a study participant, irrespective of the relationship between 
872 
the adverse event and the device(s) under investigation (section 12.2) for reportable adverse events 
873 
for this protocol). 
874 
Positive pregnancy test will not be considered an adverse event.  
875 
 Serious Adverse Event (SAE) 
876 
 Any untoward medical occurrence that: 
877 
• Results in death. 
878 
• Is life-threatening; (a non-life-threatening event which, had it been more severe, might 
879 
have become life-threatening, is not necessarily considered a serious adverse event). 
880 
• Requires inpatient hospitalization or prolongation of existing hospitalization. 
881 
• Results in persistent or significant disability/incapacity or substantial disruption of the 
882 
ability to conduct normal life functions (life threatening). 
883 
• Is a congenital anomaly or birth defect. 
884 
• Is considered a significant medical event by the investigator based on medical judgment 
885 
(e.g., may jeopardize the participant or may require medical/surgical intervention to 
886 
prevent one of the outcomes listed above). 
887 
 Unanticipated Adverse Device Effect (UADE) 
888 
Any serious adverse effect on health or safety or any life-threatening problem or death caused by, 
889 
or associated with, a device, if that effect, problem, or death was not previously identified in nature, 
890 
severity, or degree of incidence in the investigational plan or application (including a 
891 
supplementary plan or application), or any other unanticipated serious problem associated with a 
892 
device that relates to the rights, safety, or welfare of participants (21 CFR 812.3(s)). 
893 
 Adverse Device Effect (ADE) 
894 
Any untoward medical occurrence in a study participant which the device may have caused or to 
895 
which the device may have contributed. 
896 
 Device Complaints and Malfunctions 
897 
A device complication or complaint is something that happens to a device or related to device 
898 
performance, whereas an adverse event happens to a participant. A device complaint may occur 
899 
independently from an AE, or along with an AE. An AE may occur without a device complaint or 
900 
there may be an AE related to a device complaint. A device malfunction is any failure of a device 
901 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 44 of 60 
 
to meet its performance specifications or otherwise perform as intended. Performance 
902 
specifications include all claims made in the labeling for the device. The intended performance of 
903 
a device refers to the intended use for which the device is labeled or marketed. (21 CFR 803.3).   
904 
 
905 
For this protocol, a reportable adverse event includes any untoward medical occurrence that meets 
906 
one of the following criteria: 
907 
• A serious adverse event as defined in section 12.1.2. 
908 
• An Adverse Device Effect as defined in section 12.1.4, unless excluded from reporting 
909 
in section 12.7. 
910 
• An Adverse Event as defined in section 12.1.1 occurring in association with a study 
911 
procedure. 
912 
• An AE as defined in section 12.1.1 which leads to discontinuation of a study device for 
913 
4 or more hours during the hotel phase and 12 or more hours during the at home phase. 
914 
• Hypoglycemia meeting the definition of severe hypoglycemia as defined in section 
915 
12.2.1 
916 
• Diabetic ketoacidosis (DKA) as defined in section 12.2.2 or in the absence of DKA, a 
917 
hyperglycemic or ketosis event meeting the criteria defined below. 
918 
Hypoglycemia and hyperglycemia not meeting the criteria below will not be recorded as adverse 
919 
events unless associated with an Adverse Device Effect. Skin reactions from sensor placement are 
920 
only reportable if severe and/or required treatment. 
921 
 Hypoglycemia Event 
922 
Hypoglycemia not associated with an Adverse Device Effect is only reportable as an adverse event 
923 
when the following definition for severe hypoglycemia is met:   
924 
• The event required assistance of another person due to altered consciousness, and 
925 
required another person to actively administer carbohydrate, glucagon, or other 
926 
resuscitative actions. 
927 
• Impaired cognitively to the point that he/she was unable to treat himself/herself, was 
928 
unable to verbalize his/ her needs, was incoherent, disoriented, and/or combative, or 
929 
experienced seizure or coma. These episodes may be associated with sufficient 
930 
neuroglycopenia to induce seizure or coma. 
931 
• 
If plasma glucose measurements are not available during such an event, neurological 
932 
recovery attributable to the restoration of plasma glucose to normal is considered 
933 
sufficient evidence that the event was induced by a low plasma glucose concentration. 
934 
 Hyperglycemia Events/Diabetes Ketoacidosis 
935 
Hyperglycemia not associated with an Adverse Device Effect is only reportable as an adverse 
936 
event when one of the following four criteria is met:  
937 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 45 of 60 
 
• The event involved DKA, as defined by the Diabetes Control and Complications Trial 
938 
(DCCT) and described below. 
939 
• Evaluation or treatment was obtained at a health care provider facility for an acute event 
940 
involving hyperglycemia or ketosis. 
941 
• Blood ketone level ≥1.5 mmol/L and communication occurred with a health care 
942 
provider at the time of the event. 
943 
• Blood ketone level ≥3.0 mmol/L, even if there was no communication with a health 
944 
care provider. 
945 
Hyperglycemic events are classified as DKA if the following are present: 
946 
• Symptoms such as polyuria, polydipsia, nausea, or vomiting. 
947 
• Serum ketones ≥1.5 mmol/L or large/moderate urine ketones. 
948 
• Either arterial blood pH <7.30 or venous pH <7.24 or serum bicarbonate <15. 
949 
• Treatment provided in a health care facility. 
950 
All reportable Adverse Events—whether volunteered by the participant, discovered by study 
951 
personnel during questioning, or detected through physical examination, laboratory test, or other 
952 
means—will be reported on an adverse event form online.  Each adverse event form is reviewed 
953 
by the Medical Monitor to verify the coding and the reporting that is required. 
954 
 
955 
The study investigator will review each adverse event and assess the relationship of any adverse 
956 
event to be related or unrelated by determining if there is a reasonable possibility that the adverse 
957 
event may have been caused by the study device. 
958 
To ensure consistency of adverse event causality assessments, investigators should apply the 
959 
following general guideline when determining whether an adverse event is related: 
960 
• RELATED: There is a plausible temporal relationship between the onset of the adverse 
961 
event and the study intervention, and the adverse event cannot be readily explained by 
962 
the participant’s clinical state, intercurrent illness, or concomitant therapies; and/or the 
963 
adverse event follows a known pattern of response to the study intervention; and/or the 
964 
adverse event abates or resolves upon discontinuation of the study intervention or dose 
965 
reduction and, if applicable, reappears upon re-challenge. 
966 
• UNRELATED: Evidence exists that the adverse event has an etiology other than the 
967 
study intervention (e.g., preexisting medical condition, underlying disease, intercurrent 
968 
illness, or concomitant medication); and/or the adverse event has no plausible temporal 
969 
relationship to study intervention. 
970 
 
971 
The intensity of an adverse event will be rated on a three-point scale: (1) mild, (2) moderate, or (3) 
972 
severe.  It is emphasized that the term severe is a measure of intensity: thus, a severe adverse event 
973 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 46 of 60 
 
is not necessarily serious. For example, itching for several days may be rated as severe, but may 
974 
not be clinically serious. 
975 
• MILD: Usually transient, requires no special treatment, and does not interfere with the 
976 
participant’s daily activities. 
977 
• MODERATE: Usually causes a low level of inconvenience or concern to the 
978 
participant and may interfere with daily activities but is usually ameliorated by simple 
979 
therapeutic measures. 
980 
• SEVERE: Interrupts a participant’s usual daily activities and generally requires 
981 
systemic drug therapy or other treatment. 
982 
 
983 
Adverse events will be coded per standard categories (i.e., mild, moderate, severe).  The Medical 
984 
Monitor will review the investigator’s assessment of causality and may agree or disagree.  Both 
985 
the investigators and Medical Monitor’s assessments will be recorded.  The Medical Monitor will 
986 
have the final say in determining the causality. 
987 
Adverse events that continue after the participant’s discontinuation or completion of the study will 
988 
be followed until their medical outcome is determined or until no further change in the condition 
989 
is expected. 
990 
 
991 
The outcome of each reportable adverse event will be classified by the investigator as follows: 
992 
• RECOVERED/RESOLVED – The participant recovered from the AE/SAE without 
993 
sequelae.  Record the AE/SAE stop date. 
994 
• RECOVERED/RESOLVED WITH SEQUELAE – The event persisted and stabilized 
995 
without change in the event anticipated.  Record the AE/SAE stop date. 
996 
• FATAL – A fatal outcome is defined as the SAE that resulted in death. Only the event 
997 
that was the cause of death should be reported as fatal. AEs/SAEs that were ongoing at 
998 
the time of death; however, were not the cause of death, will be recorded as “resolved” 
999 
at the time of death. 
1000 
• NOT RECOVERED/NOT RESOLVED (ONGOING) – An ongoing AE/SAE is 
1001 
defined as the event was ongoing with an undetermined outcome. 
1002 
• An ongoing outcome will require follow-up by the site in order to determine the final 
1003 
outcome of the AE/SAE. 
1004 
• The outcome of an ongoing event at the time of death that was not the cause of death, 
1005 
will be updated and recorded as “resolved” with the date of death recorded as the stop 
1006 
date. 
1007 
• UNKNOWN – An unknown outcome is defined as an inability to access the participant 
1008 
or the participant’s records to determine the outcome (for example, a participant that 
1009 
was lost to follow-up). 
1010 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 47 of 60 
 
All clinically significant abnormalities of clinical laboratory measurements or adverse events 
1011 
occurring during the study and continuing at study termination should be followed by the 
1012 
participant’s physician and evaluated with additional tests (if necessary) until diagnosis of the 
1013 
underlying cause, or resolution.  Follow-up information should be recorded on source documents. 
1014 
If any reported adverse events are present when a participant completes the study, or if a participant 
1015 
is withdrawn from the study due to an adverse event, the participant will be contacted for re-
1016 
evaluation within 2 weeks. If the adverse event has not been resolved, additional follow-up will be 
1017 
performed as appropriate.  Every effort should be made by the Investigator or delegate to contact 
1018 
the participant until the adverse event has resolved or stabilized. 
1019 
 
1020 
All UADEs, ADEs, device complaints, and device malfunctions will be reported irrespective of 
1021 
whether an adverse event occurred, except in the following circumstances. 
1022 
The following device issues are anticipated and will not be reported but will report as an Adverse 
1023 
Event if the criteria for AE reporting described above are met: 
1024 
• Component disconnections 
1025 
• CGM sensors lasting fewer than the number of days expected per CGM labeling 
1026 
• CGM tape adherence issues 
1027 
• Pump infusion set occlusion not leading to ketosis 
1028 
• Battery lifespan deficiency due to inadequate charging or extensive wireless 
1029 
communication 
1030 
• Intermittent device component disconnections/communication failures not leading to 
1031 
system replacement 
1032 
• Device issues clearly addressed in the user guide manual that do not require additional 
1033 
troubleshooting 
1034 
• Skin reactions from CGM sensor placement or pump infusion set placement that do not 
1035 
meet criteria for AE reporting 
1036 
 
1037 
• UADEs must be reported within 10 working days to the FDA after the sponsor first 
1038 
receives notice of the adverse effect. 
1039 
• Other reportable adverse events, device malfunctions (with or without an adverse 
1040 
event) and device complaints should be reported promptly, but there is no formal 
1041 
required reporting period. 
1042 
• The IDE Sponsor will investigate the UADE and if indicated, report the results of the 
1043 
investigation to the IRBs, FDA, and Medical Monitor within 10 working days of the 
1044 
study team becoming aware of the UADE per 21CFR 812.46(b) (2).  
1045 
• The Medical Monitor will determine if the UADE presents an unreasonable risk to 
1046 
participants. If so, the Medical Monitor must ensure that all investigations, or parts of 
1047 
investigations presenting that risk, are terminated as soon as possible but no later than 
1048 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 48 of 60 
 
5 working days after the Medical Monitor makes this determination and no later than 
1049 
15 working days after first receipt notice of the UADE. 
1050 
• In the case of a device system component malfunction (e.g. pump, CGM, control 
1051 
algorithm), information will be forwarded to the responsible manufacturer by the study 
1052 
personnel. 
1053 
 
1054 
 Participant Discontinuation  
1055 
A participant will be discontinued if any of the following occur: 
1056 
• The investigator believes it is unsafe for the participant to continue the intervention.  
1057 
This could be due to the development of a new medical condition or worsening of an 
1058 
existing condition; or participant behavior contrary to the indications for use of the 
1059 
device that imposes on the participant’s safety 
1060 
• The participant requests that the treatment be stopped 
1061 
• Two distinct episodes of DKA 
1062 
• Two distinct severe hypoglycemia events as defined in section 12.2.1. 
1063 
• Two events of any kind: severe hypoglycemia or DKA 
1064 
 Suspending/Stopping Overall Study 
1065 
In the case of an unanticipated system malfunction resulting in a severe hypoglycemia or severe 
1066 
hyperglycemia event (as defined in section 12.2.2), use of the study device system will be 
1067 
suspended while the problem is diagnosed. 
1068 
In the event that two distinct episodes of DKA or two distinct severe hypoglycemia events as 
1069 
defined in section 12.2.1 occur, the overall study would be suspended while the underlying 
1070 
conditions are determined.   
1071 
In addition, study activities could be similarly suspended if the manufacturer of any constituent 
1072 
study device requires stoppage of device use for safety reasons (e.g., product recall). The affected 
1073 
study activities may resume if the underlying problem can be corrected by a protocol or system 
1074 
modification that will not invalidate the results obtained prior to suspension. The study Medical 
1075 
Monitor will review all adverse events and adverse device events that are reported during the study 
1076 
and will review compiled safety data at periodic intervals. The Medical Monitor may request 
1077 
suspension of study activities or stoppage of the study if deemed necessary based on the totality 
1078 
of safety data available. 
1079 
 
1080 
A Medical Monitor will review all DKA and severe hypoglycemia irrespective of relatedness to 
1081 
study device use, and all serious events (including UADEs) related to study device use at the time 
1082 
of occurrence. The Medical Monitor can request modifications to the study protocol or suspension 
1083 
or outright stoppage of the study if deemed necessary based on the totality of safety data available. 
1084 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 49 of 60 
 
Details regarding the Medical Monitor review will be documented in a separate Medical Monitor 
1085 
document.   
1086 
 
1087 
A data breach is defined in the HITECH Act (43 USC 17932) as an unauthorized acquisition, 
1088 
access, or use of protected health information (PHI) that compromises the security or privacy of 
1089 
such information.   
 
1090 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 50 of 60 
 
Chapter 13:  Miscellaneous Considerations  
1091 
 
1092 
Participants using glulisine at the time of enrollment will be asked to contact their personal 
1093 
physician to change their prescribed personal insulin to lispro or aspart for the duration of the trial. 
1094 
The study devices (study insulin pump, study CGM) must be removed before Magnetic Resonance 
1095 
Imaging (MRI), Computed Tomography (CT) or diathermy treatment. Participants may continue 
1096 
in the trial after temporarily discontinuing use if requiring one of the treatments above. 
1097 
 
1098 
Participation in the study is voluntary. Participant may withdraw at any time.  For participants who 
1099 
do withdraw from the study, the study team will determine if their data will be used in analysis.  
1100 
 
1101 
For security and confidentiality purposes, subjects will be assigned an identifier that will be used 
1102 
instead of their name.  Protected health information gathered for this study may be shared with the 
1103 
third-party collaborators.  De-identified subject information may also be provided to collaborators 
1104 
involved in the study after the appropriate research agreement has been executed. 
1105 
 
1106 
If a participant is lost to follow up and participant outcome cannot be determined, outcome 
1107 
classification will be the last known outcome/contact with the participant. A participant will be 
1108 
considered lost to follow-up after three attempted contacts that do not result in any communication 
1109 
from the participant. A certified letter may be sent as the fourth and final attempt to communicate 
1110 
with the participant.  
 
1111 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 51 of 60 
 
Chapter 14: Statistical Consideration 
1112 
 
1113 
The proposed work is a safety and feasibility study of the FCL system and is not intended to be 
1114 
powered to fully demonstrate efficacy of the system. The sample size of up to 6 participants per 
1115 
session at each site was selected based on previous experience of the feasible number of individuals 
1116 
to supervise at one time under similar study conditions.  
1117 
 Planned Analysis 
1118 
The primary outcome of interest will be the change in the mean CGM between the week of the 
1119 
Usual Care observational period and the week of AIDANET at-home. This study represents a 
1120 
small pilot study to assess the safety and efficacy of the small-version AIDANET system and is 
1121 
not formally powered. Nevertheless, the randomized crossover design will allow for analysis of 
1122 
period effects between Group A and Group B. Comparison between these groups will be made to 
1123 
determine if a period effect can explain part of the benefit of the FCL system during the at-home 
1124 
period. 
1125 
a. Null Hypothesis: There is no difference in the mean CGM between the week of 
1126 
Usual Care observational period and the at-home FCL period. 
1127 
b. Alternative Hypothesis: There is a difference in the mean CGM between the week 
1128 
of Usual Care observational period and the at-home FCL period. 
1129 
Analysis will involve use of repeated measure ANOVA models to predict CGM average and TIR 
1130 
with the FCL status a fixed effect and baseline HbA1c and gender as covariates. 
1131 
Secondary outcomes: 
1132 
All secondary outcomes will be similarly analyzed. If an outcomes distribution is not suited for 
1133 
mixed model analysis (e.g., profound skewness, or large atom at boundary) we will perform paired 
1134 
Wilcoxon signed rank test (and loose the capacity to use covariate) to test difference in the median 
1135 
instead of the mean; this is expected for time below 70mg/dL, number of hypoglycemia, and 
1136 
possibly time above 250mg/dL. 
1137 
We do not plan to correct for multiple comparisons. 
1138 
We do not expect substantial missing values in this supervised study, but if more than 3 participants 
1139 
have one or more missing admissions, we will consider switching from RANOVA to mixed model 
1140 
repeated measures. 
1141 
 
1142 
As an early exploratory study, the goal will be to complete 6 participants to provide data from a 
1143 
variety of individuals. This number was chosen out of feasibility and not from a formal power 
1144 
calculation. The total sample size of 6 participants was selected based on previous experience of 
1145 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 52 of 60 
 
the number of participants necessary to satisfy FDA requirements for a safety and feasibility study 
1146 
and move onto a larger out-patient efficacy study. While this sample size is thus a convenience 
1147 
sample, we may still determine the power to analyze each of the study hypotheses based on pilot 
1148 
trial data. 
1149 
 
1150 
 Primary Efficacy Endpoint 
1151 
The primary metric for analysis will be change in mean CGM between the second last 7 days week 
1152 
of the control Usual-Care period and the one-week Remote Monitored At-Home FCL period. 
1153 
 Secondary Outcomes 
1154 
Glycemic Metrics will be obtained directly from CGM data and will include the standard metrics 
1155 
recommended by the international consensus on CGM including mean CGM, GMI derived from 
1156 
mean CGM, time in range 70-180 mg/dL, CGM standard deviation (StDev), CGM coefficient of 
1157 
variation (CV), CGM %<54 mg/dL, CGM %<70 mg/dL, CGM %>180 mg/dL, and CGM %>250 
1158 
mg/dL. For the Usual Care period, CGM data will be obtained from either the participant’s 
1159 
personal CGM or a study provided CGM. Data for the control Usual-Care period will be analyzed 
1160 
by last available 7-day period. During the FCL period, CGM data will be obtained directly from 
1161 
the study device. As GMI is a linear transformation of mean CGM, this metric will have the same 
1162 
effect and will be presented as a primary outcome as well. All other glycemic metrics will be 
1163 
considered secondary outcome measures. 
1164 
Device-Use Metrics will include time in automation, total daily insulin dose, and number of 
1165 
boluses per day. During the Usual Care period, participants using an insulin pump will have their 
1166 
pump uploaded at the end of the period to capture their insulin delivery and bolus data. The FCL 
1167 
period, insulin use, and bolus data (if any) will be captured from the experimental device. 
1168 
Exercise Challenge Metrics will include the duration of exercise, approximate intensity of exercise 
1169 
(low, moderate, or high intensity), the % CGM<70 mg/dL, % CGM<54 mg/dL, and any episodes 
1170 
of SH (CGM<70mg/dL for more than 15 minutes with interruption, CGM≥70, of less than 15 
1171 
minutes or CHO treatment) during and 2 hours after the exercise challenges. 
1172 
Unannounced Meal Metrics during the supervised house/hotel FLC stage participants will be 
1173 
instructed to eat at least 3 meals per day. The time of completion for these meals will be recorded 
1174 
by study staff. The % CGM>250 mg/dL for the 4 hours after each meal will be recorded and 
1175 
specifically analyzed. Participants will be instructed to freely eat meals during the supervised at-
1176 
home FCL stage but will not be required to record the timing of the meals for unannounced meals. 
1177 
Patient Reported Outcomes will include several surveys aiming to capture participant satisfaction 
1178 
with the FCL device and any changes in distress or burden of diabetes management. See 
1179 
APPENDIX for survey tools. These surveys will include: 
1180 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 53 of 60 
 
a. The INSPIRE Measures: A validated tool assessing the positive expectancies of AID 
1181 
systems for youth, adults, and parents and partners of people with diabetes. This tool 
1182 
has been specifically endorsed by the FDA for use with developing insulin-dosing 
1183 
systems. 
1184 
b. Technology Expectations Surveys: A 25 question self-report measure of 
1185 
expectations from advanced technologies and perceived impact of the technology on 
1186 
quality of life. Validated to age 13+ years. 
1187 
These surveys will be administered at baseline and then at the end of the prior to or at the start of 
1188 
the 1-week supervised House/Hotel FCL period and at the end of the 1-week remote-monitored 
1189 
at-home FCL study 
1190 
 CGM Data Treatment 
1191 
a. Saturated CGM values “High” and “Low” will be replaced by 401mg/dL and 
1192 
39mg/dL respectively.  
1193 
b. Any CGM gaps shorter than 1 hour will be interpolated  
1194 
c. CGM data during recorded occlusion event will be removed from analysis as 
1195 
follows: any measurement less than 2h before or after the time of record will be 
1196 
removed. 
1197 
d. CGM data following a pump/DiAs communication interruption >1h by less than 2h 
1198 
will be removed 
1199 
 Outcome Computation Conditions 
1200 
Outcomes will only be computed if at least 80% of the analysis window CGM measurements (after 
1201 
data treatment) are available. 
1202 
 
1203 
We will assess for the system’s functionality, including the ability of the system to run its code 
1204 
without error (delivering insulin safely, as planned), as well as its ability to avoid low BG <70 
1205 
mg/dL. 
1206 
 
1207 
Baseline demographic and clinical characteristics of the cohort of all randomized participants will 
1208 
be summarized in a table using summary statistics appropriate to the distribution of each variable. 
1209 
Descriptive statistics will be displayed overall and by treatment group. 
1210 
Will include: 
1211 
a. Age 
1212 
b. HbA1c 
1213 
c. Gender 
1214 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 54 of 60 
 
d. Race/ethnicity 
1215 
e. CGM use before enrollment 
1216 
f. AID use before enrollment 
1217 
g. Diabetes duration 
1218 
h. BMI 
1219 
i. Total Daily Insulin 
1220 
 
1221 
The following tabulations and analyses will be performed during time on the UVa AP systems to 
1222 
assess device issues: 
1223 
a. Device malfunctions requiring study team contact and other reported device issues 
1224 
b. % time CGM data available 
1225 
c. % time with closed loop control  
 
1226 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 55 of 60 
 
Chapter 15: Data Collection and Monitoring 
1227 
 
1228 
The study data are collected through a combination of case report forms (electronic and paper) and 
1229 
electronic device data files obtained from the software and individual hardware components.  
1230 
These electronic device files and electronic CRFs are considered the primary source 
1231 
documentation. 
1232 
When data are directly collected in electronic case report forms, this will be considered the source 
1233 
data.  Records will be maintained in accordance with ICH E6 and institutional regulatory 
1234 
requirements for the protection of confidentiality of participants. 
1235 
 
1236 
Study documents should be retained for a minimum of 2 years after the last approval of a marketing 
1237 
application in an ICH region and until there are no pending or contemplated marketing applications 
1238 
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical 
1239 
development of the investigational product.  These documents should be retained for a longer 
1240 
period, however, if required by local regulations.  No records will be destroyed without the written 
1241 
consent of the sponsor, if applicable.  It is the responsibility of the sponsor to inform the 
1242 
investigator when these documents no longer need to be retained. 
1243 
 
1244 
A protocol deviation is any noncompliance with the clinical trial protocol, Good Clinical Practices 
1245 
(GCP), or procedure requirements.  The noncompliance may be either on the part of the participant, 
1246 
the investigator, or the study site staff.  As a result of deviations, corrective actions may be 
1247 
developed by the site and implemented as appropriate.  Major deviations will be reported to the 
1248 
IRB-HSR within 7 calendar days of when the study team becomes aware of the event.  
1249 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 56 of 60 
 
Chapter 16: Ethics/Protection of Human Participants 
1250 
 
1251 
The investigator will ensure that this study is conducted in full conformity with Regulations for 
1252 
the Protection of Human Participants of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 
1253 
CFR Part 56, and/or the ICH E6. 
1254 
 
1255 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
1256 
be submitted to the IRB for review and approval.  Approval of both the protocol and the consent 
1257 
form must be obtained before any participant is enrolled.  Any amendment to the protocol will 
1258 
require review and approval by the IRB before the changes are implemented to the study.  All 
1259 
changes to the consent form will be IRB approved; a determination will be made regarding whether 
1260 
previously consented participants need to be re-consented. 
1261 
 
1262 
 Consent Procedures and Documentation 
1263 
Informed consent is a process that is initiated prior to an individual’s agreement to participate in 
1264 
the study and continues throughout the individual’s study participation. The potential participant 
1265 
will be provided with a short overview of the study including its study goals, study procedures, 
1266 
and study timeline. If the potential participant remains interested, they will be asked permission to 
1267 
review inclusion/exclusion criteria to assess if they are eligible to participate in the study. If 
1268 
permission is granted, the study team will review the Inclusion/Exclusion criteria (section 3.4 and 
1269 
3.5). If eligible, the study team member will provide a copy of the informed consent form (e.g., in 
1270 
person, email, fax, or mail) to the potential participant for their review. Potential participants may 
1271 
also elect to review the informed consent form prior to discussing pre-screening questions.  
1272 
The potential participant will be provided with ample time to read and review the consent form. 
1273 
After their review, the study team will discuss the study at length in a phone call/HIPAA compliant 
1274 
telecommunication method for consenting that is not face to face. All participants will receive 
1275 
verbal explanation in terms suited to their comprehension of the purposes, procedures, and 
1276 
potential risks of the study and of their rights as research participants. Extensive discussion of risks 
1277 
and possible benefits of participation will be provided. The potential participant will be given an 
1278 
opportunity to ask the study team questions or may speak directly with the study physician. The 
1279 
potential participant’s understanding of the information presented in the process of consent will be 
1280 
assessed by asking open-ended questions.  
1281 
The consent form may be signed electronically for both in-person and telecommunication 
1282 
screening visits. Note: For potential participants who are not able to sign an electronic consent 
1283 
form, in-person, email, fax, or mail will be alternatives used to obtain a signed consent. A HIPAA 
1284 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 57 of 60 
 
compliant video conferencing tool (e.g., Zoom, WebEx) will be utilized during the consenting 
1285 
process of the telecommunication screening visit to facilitate the FDA Part 11 compliant process 
1286 
of verification of reviewing two forms of identification if signing electronically off site. 
1287 
Participants can download a PDF copy of the signed consent and automatically receive a PDF via 
1288 
email from REDCap after the form is completed. CRCs also could download, print, and mail a 
1289 
paper copy for each participant. Study procedures may begin once the consent has been signed by 
1290 
the participant and a member of the study team.  
1291 
The rights and welfare of the participants will be protected by emphasizing to them that the quality 
1292 
of their medical care will not be adversely affected if they decline to participate in this study. 
1293 
 
1294 
The IRB-HSR Post Approval Monitoring (PAM) auditors, representatives of the IRB, or device 
1295 
company supplying study product may inspect documents and records required to be maintained 
1296 
by the investigator, including but not limited to, medical records (office, clinic, or hospital) for the 
1297 
participants in this study.   
1298 
The study participant’s contact information will be securely stored at the clinical site for internal 
1299 
use during the study. At the end of the study, all records will continue to be kept in a secure location 
1300 
for as long a period as dictated by local IRB and institutional regulations. The study data entry and 
1301 
study management systems used by research staff will be secured and password protected. At the 
1302 
end of the study, all study databases will be archived at the UVA CDT. 
 
1303 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 58 of 60 
 
Chapter 17: References  
1304 
1. Rogers MAM, Kim C, Banerjee T, Lee JM. Fluctuations in the incidence of type 1 diabetes in the 
1305 
United States from 2001 to 2015: a longitudinal study. BMC medicine. 2017;15(1):199. 
1306 
2. Forlenza GP, Rewers M. The epidemic of type 1 diabetes: what is it telling us? Current opinion in 
1307 
endocrinology, diabetes, and obesity. 2011;18(4):248-51. 
1308 
3. Committee ADAPP. 6. Glycemic Targets: Standards of Medical Care in Diabetes—2022. Diabetes 
1309 
Care. 2021;45(Supplement_1):S83-S96. 
1310 
4. Committee ADAPP. 14. Children and Adolescents: Standards of Medical Care in Diabetes—2022. 
1311 
Diabetes Care. 2021;45(Supplement_1):S208-S31. 
1312 
5. Malik FS, Sauder KA, Isom S, Reboussin BA, Dabelea D, Lawrence JM, et al. Trends in Glycemic 
1313 
Control Among Youth and Young Adults With Diabetes: The SEARCH for Diabetes in Youth Study. 
1314 
Diabetes Care. 2022;45(2):285-94. 
1315 
6. Sawyer A, Sobczak M, Forlenza GP, Alonso GT. Glycemic Control in Relation to Technology Use in 
1316 
a Single Center Cohort of Children With Type 1 Diabetes. Diabetes technology & therapeutics. 2022. 
1317 
7. The effect of intensive treatment of diabetes on the development and progression of long-term 
1318 
complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial 
1319 
Research Group. N Engl J Med. 1993;329(14):977-86. 
1320 
8. Lachin JM, Genuth S, Nathan DM, Zinman B, Rutledge BN. Effect of glycemic exposure on the risk 
1321 
of microvascular complications in the diabetes control and complications trial--revisited. Diabetes. 
1322 
2008;57(4):995-1001. 
1323 
9. Pop-Busui R, Herman WH, Feldman EL, Low PA, Martin CL, Cleary PA, et al. DCCT and EDIC 
1324 
studies in type 1 diabetes: lessons for diabetic neuropathy regarding metabolic memory and natural 
1325 
history. Current diabetes reports. 2010;10(4):276-82. 
1326 
10. Jacobson AM, Braffett BH, Cleary PA, Gubitosi-Klug RA, Larkin ME. The long-term effects of type 
1327 
1 diabetes treatment and complications on health-related quality of life: a 23-year follow-up of the 
1328 
Diabetes Control and Complications/Epidemiology of Diabetes Interventions and Complications 
1329 
cohort. Diabetes Care. 2013;36(10):3131-8. 
1330 
11. Nathan DM, Bayless M, Cleary P, Genuth S, Gubitosi-Klug R, Lachin JM, et al. Diabetes control and 
1331 
complications trial/epidemiology of diabetes interventions and complications study at 30 years: 
1332 
advances and contributions. Diabetes. 2013;62(12):3976-86. 
1333 
12. Nathan DM. The diabetes control and complications trial/epidemiology of diabetes interventions and 
1334 
complications study at 30 years: overview. Diabetes Care. 2014;37(1):9-16. 
1335 
13. Berget C, Messer LH, Forlenza GP. A Clinical Overview of Insulin Pump Therapy for the Management 
1336 
of Diabetes: Past, Present, and Future of Intensive Therapy. Diabetes spectrum : a publication of the 
1337 
American Diabetes Association. 2019;32(3):194-204. 
1338 
14. Forlenza GP, Kushner T, Messer LH, Wadwa RP, Sankaranarayanan S. Factory-Calibrated Continuous 
1339 
Glucose Monitoring: How and Why It Works, and the Dangers of Reuse Beyond Approved Duration 
1340 
of Wear. Diabetes technology & therapeutics. 2019. 
1341 
15. Forlenza GP, Lal RA. Current Status and Emerging Options for Automated Insulin Delivery Systems. 
1342 
Diabetes technology & therapeutics. 2022. 
1343 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 59 of 60 
 
16. Kowalski A. Pathway to artificial pancreas systems revisited: moving downstream. Diabetes Care. 
1344 
2015;38(6):1036-43. 
1345 
17. Kowalski AJ. Can we really close the loop and how soon? Accelerating the availability of an artificial 
1346 
pancreas: a roadmap to better diabetes outcomes. Diabetes technology & therapeutics. 2009;11 Suppl 
1347 
1:S113-9. 
1348 
18. Ware J, Allen JM, Boughton CK, Wilinska ME, Hartnell S, Thankamony A, et al. Randomized Trial 
1349 
of Closed-Loop Control in Very Young Children with Type 1 Diabetes. N Engl J Med. 
1350 
2022;386(3):209-19. 
1351 
19. Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, et al. Six-Month 
1352 
Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes. N Engl J Med. 2019. 
1353 
20. Breton MD, Kanapka LG, Beck RW, Ekhlaspour L, Forlenza GP, Cengiz E, et al. A Randomized Trial 
1354 
of Closed-Loop Control in Children with Type 1 Diabetes. N Engl J Med. 2020;383(9):836-45. 
1355 
21. McAuley SA, Trawley S, Vogrin S, Ward GM, Fourlanos S, A. Grills C, et al. Closed-Loop Insulin 
1356 
Delivery Versus Sensor-Augmented Pump Therapy in Older Adults With Type 1 Diabetes (ORACL): 
1357 
A Randomized, Crossover Trial. Diabetes Care. 2021:dc211667. 
1358 
22. Collyns OJ, Meier RA, Betts ZL, Chan DSH, Frampton C, Frewen CM, et al. Improved Glycemic 
1359 
Outcomes With Medtronic MiniMed Advanced Hybrid Closed-Loop Delivery: Results From a 
1360 
Randomized Crossover Trial Comparing Automated Insulin Delivery With Predictive Low Glucose 
1361 
Suspend in People With Type 1 Diabetes. Diabetes Care. 2021;44(4):969-75. 
1362 
23. McAuley SA, Lee MH, Paldus B, Vogrin S, de Bock MI, Abraham MB, et al. Six Months of Hybrid 
1363 
Closed-Loop Versus Manual Insulin Delivery With Fingerprick Blood Glucose Monitoring in Adults 
1364 
With Type 1 Diabetes: A Randomized, Controlled Trial. Diabetes Care. 2020;43(12):3024-33. 
1365 
24. Messer LH, Berget C, Pyle L, Vigers T, Cobry E, Driscoll KA, et al. Real-World Use of a New Hybrid 
1366 
Closed Loop Improves Glycemic Control in Youth with Type 1 Diabetes. Diabetes technology & 
1367 
therapeutics. 2021. 
1368 
25. Da Silva J, Lepore G, Battelino T, Arrieta A, Castañeda J, Grosman B, et al. Real-world Performance 
1369 
of the MiniMed™ 780G System: First Report of Outcomes from 4'120 Users. Diabetes technology & 
1370 
therapeutics. 2021. 
1371 
26. Breton MD, Kovatchev BP. One Year Real-World Use of the Control-IQ Advanced Hybrid Closed-
1372 
Loop Technology. Diabetes technology & therapeutics. 2021. 
1373 
27. Berget C, Akturk HK, Messer LH, Vigers T, Pyle L, Snell-Bergeon J, et al. Real world performance of 
1374 
hybrid closed loop in youth, young adults, adults and older adults with type 1 diabetes: Identifying a 
1375 
clinical target for hybrid closed loop use. Diabetes, obesity & metabolism. 2021. 
1376 
28. Amadou C, Franc S, Benhamou PY, Lablanche S, Huneker E, Charpentier G, et al. Diabeloop DBLG1 
1377 
Closed-Loop System Enables Patients With Type 1 Diabetes to Significantly Improve Their Glycemic 
1378 
Control in Real-Life Situations Without Serious Adverse Events: 6-Month Follow-up. Diabetes Care. 
1379 
2021;44(3):844-6. 
1380 
29. Stone MP, Agrawal P, Chen X, Liu M, Shin J, Cordero TL, et al. Retrospective Analysis of 3-Month 
1381 
Real-World Glucose Data After the MiniMed 670G System Commercial Launch. Diabetes technology 
1382 
& therapeutics. 2018;20(10):689-92. 
1383 
30. Forlenza GP, Breton MD, Kovatchev B. Candidate Selection for Hybrid Closed Loop Systems. 
1384 
Diabetes technology & therapeutics. 2021. 
1385 

CLINICAL PROTOCOL 
 
 
MiniNET_25-Oct-2024 
 
Page 60 of 60 
 
31. Fredette ME, Zonfrillo MR, Park S, Quintos JB, Gruppuso PA, Topor LS. Self-reported insulin pump 
1386 
prescribing practices in pediatric type 1 diabetes. Pediatr Diabetes. 2021. 
1387 
32. Pauley ME, Berget C, Messer LH, Forlenza GP. Barriers to Uptake of Insulin Technologies and Novel 
1388 
Solutions. Med Devices (Auckl). 2021;14:339-54. 
1389