Safety and Efficacy of Initializing the Control-IQ Artificial Pancreas System Using Total Daily Insulin
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Sponsor: University of Virginia

 
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Safety and Efficacy of Initializing the 
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Control-IQ Artificial Pancreas System Using 
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Total Daily Insulin 
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Participating Institutions 
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University of Virginia Center for Diabetes Technology 
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NCT03804983 
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Version Number: v1.4 
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2/7/2019 
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UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
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KEY ROLES 
24 
 
Protocol Sponsor/Chair 
 
Name, degree 
Marc Breton, PhD 
Institution Name 
University of Virginia 
 
Study Licensed Medical Investigator  
 
Name, degree 
Melissa Schoelwer, MD 
Institution Name 
University of Virginia 
 
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UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
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TABLE OF CONTENTS 
26 
CHAPTER 1: BACKGROUND INFORMATION ............................................................................................ 13 
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1.1 Introduction .......................................................................................................................... 13 
28 
1.2 Rationale .............................................................................................................................. 15 
29 
1.3 Potential Risks and Benefits of the Investigational Device ................................................. 15 
30 
1.3.1 Known Potential Risks ................................................................................................... 16 
31 
1.3.1.1 Venipuncture Risks ................................................................................................ 16 
32 
1.3.1.2 Fingerstick Risks .................................................................................................... 16 
33 
1.3.1.3 Subcutaneous Catheter Risks (CGM) .................................................................... 16 
34 
1.3.1.4 Risk of Hypoglycemia ........................................................................................... 16 
35 
1.3.1.5 Risk of Hyperglycemia .......................................................................................... 16 
36 
1.3.1.6 Risk of Device Reuse ............................................................................................. 17 
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1.3.1.7 Risk of Injury during Ski/Snowboarding ............................................................... 17 
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1.3.1.8 Other Risks ............................................................................................................ 17 
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1.3.2 Known Potential Benefits .............................................................................................. 17 
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1.4 General Considerations ........................................................................................................ 18 
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CHAPTER 2: STUDY ENROLLMENT AND SCREENING ............................................................................. 19 
42 
2.1 Participant Recruitment and Enrollment.............................................................................. 19 
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2.1.1 Informed Consent and Authorization Procedures .......................................................... 19 
44 
2.2 Participant Inclusion Criteria ............................................................................................... 19 
45 
2.3 Participant Exclusion Criteria .............................................................................................. 20 
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2.4 Screening Procedures ........................................................................................................... 21 
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2.4.1 Eligibility and Baseline Procedures at Screening .......................................................... 21 
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CHAPTER 3: STUDY SYSTEM TRAINING ................................................................................................. 22 
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3.1 Study Equipment Training ................................................................................................... 22 
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3.1.1 Initiation of CGM .......................................................................................................... 22 
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3.1.2 Initiation of Study Pump ................................................................................................ 22 
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3.1.3 Initiation of Activity Tracker ......................................................................................... 22 
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3.1.4 Blood Glucose and Ketone Testing ............................................................................... 23 
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3.1.5 Post-Training Check In .................................................................................................. 23 
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180030 – Winter Study 2019 v1.4 
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CHAPTER 4: SKI ADMISSION PROCEDURES ........................................................................................... 24 
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4.1 Admission Check-In Procedures ......................................................................................... 24 
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4.1.1 Participant Check-In & Verification .............................................................................. 24 
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4.1.2 Randomization ............................................................................................................... 24 
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4.2 Main Admission Activities and Procedures......................................................................... 25 
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4.2.1 General Admission Overview ........................................................................................ 25 
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4.2.2 Device Procedures for the Participants .......................................................................... 25 
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4.2.3 Participants’ Admission Itinerary .................................................................................. 25 
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CHAPTER 5: AT-HOME TREATMENT & STUDY COMPLETION .............................................................. 28 
64 
5.1 At-Home Treatment Continuation ....................................................................................... 28 
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5.1.1 Post Admission Follow-up Phone Call .......................................................................... 28 
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5.2 Final Study Visit .................................................................................................................. 28 
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5.3 Early Termination Visit (If Applicable) .............................................................................. 28 
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5.4 Unscheduled Visits .............................................................................................................. 28 
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5.5 Participant Access to Study Device at Study Closure ......................................................... 28 
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CHAPTER 6: STUDY DEVICES .................................................................................................................. 30 
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6.1 Description of the Investigational Device ........................................................................... 30 
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6.1.1 Insulin Pump .................................................................................................................. 30 
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6.1.2 Continuous Glucose Monitoring .................................................................................... 30 
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6.1.3 Blood Glucose Meter and Strips .................................................................................... 30 
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6.1.3.1 Blood Glucose Meter Testing ................................................................................ 30 
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6.1.3.2 Blood Glucose Meter Supplies .............................................................................. 30 
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6.1.4 Blood Ketone Meter and Strips...................................................................................... 30 
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6.1.4.1 Blood Ketone Testing ............................................................................................ 30 
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6.1.4.2 Blood Ketone Meter Supplies ................................................................................ 30 
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6.1.5 Activity Tracker ............................................................................................................. 31 
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6.1.6 Study Device Accountability Procedures ...................................................................... 31 
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6.1.7 Blood Ketone Testing .................................................................................................... 31 
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6.2 Safety Measures ................................................................................................................... 31 
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6.2.1 CGM Calibration ........................................................................................................... 31 
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6.2.2 System Failure ............................................................................................................... 31 
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6.2.3 Hypoglycemia Threshold Alert and Safety Protocol ..................................................... 31 
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6.2.4 Hyperglycemia Threshold Alert and Safety Protocol .................................................... 32 
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CHAPTER 7: POINT-OF-CARE TESTING .................................................................................................. 33 
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7.1 Point-of-Care Samples ......................................................................................................... 33 
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CHAPTER 8: ADVERSE EVENTS, DEVICE ISSUES, AND STOPPING RULES ............................................. 34 
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8.1 Adverse Events .................................................................................................................... 34 
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8.1.1 Definitions...................................................................................................................... 34 
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8.1.2 Reportable Adverse Events ............................................................................................ 35 
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8.1.2.1 Hypoglycemic Events ............................................................................................ 35 
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8.1.2.2 Hyperglycemic Events/Diabetic Ketoacidosis ....................................................... 35 
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8.1.3 Relationship of Adverse Event to Study Device............................................................ 36 
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8.1.4 Intensity of Adverse Event............................................................................................. 36 
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8.1.5 Coding of Adverse Events ............................................................................................. 36 
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8.1.6 Outcome of Adverse Event ............................................................................................ 36 
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8.2 Reportable Device Issues ..................................................................................................... 37 
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8.3 Pregnancy Reporting............................................................................................................ 38 
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8.4 Timing of Event Reporting .................................................................................................. 38 
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8.5 Stopping Criteria .................................................................................................................. 38 
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8.5.1 Participant Discontinuation of Study Device ................................................................. 38 
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8.5.2 Criteria for Suspending or Stopping Overall Study ....................................................... 39 
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8.6 Risks..................................................................................................................................... 39 
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CHAPTER 9: MISCELLANEOUS CONSIDERATIONS ................................................................................. 40 
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9.1 Drugs Used as Part of the Protocol ...................................................................................... 40 
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9.2 Prohibited Medications, Treatments, and Procedures ......................................................... 40 
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9.3 Participant Compensation .................................................................................................... 40 
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9.4 Participant Withdrawal ........................................................................................................ 40 
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9.5 Confidentiality ..................................................................................................................... 40 
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CHAPTER 10: STATISTICAL CONSIDERATION ........................................................................................ 41 
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180030 – Winter Study 2019 v1.4 
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10.1 Statistical and Analytical Plans.......................................................................................... 41 
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10.2 Statistical Hypotheses ........................................................................................................ 41 
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10.3 Sample Size........................................................................................................................ 41 
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10.4 Outcome Measures ............................................................................................................ 41 
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10.4.1 Primary Efficacy Endpoint .......................................................................................... 41 
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10.4.2 Secondary Efficacy Endpoints ..................................................................................... 41 
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10.4.2.1 Safety Analyses .................................................................................................... 42 
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10.5 Device Issues ..................................................................................................................... 42 
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CHAPTER 11: DATA COLLECTION AND MONITORING ........................................................................... 44 
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11.1 Case Report Forms and Device Data ................................................................................. 44 
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11.2 Study Records Retention ................................................................................................... 44 
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11.3 Protocol Deviations............................................................................................................ 44 
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CHAPTER 12: ETHICS/PROTECTION OF HUMAN PARTICIPANTS........................................................... 45 
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12.1 Ethical Standard ................................................................................................................. 45 
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12.2 Institutional Review Boards............................................................................................... 45 
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12.3 Informed Consent Process ................................................................................................. 45 
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12.3.1 Consent Procedures and Documentation ..................................................................... 45 
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12.3.2 Participant and Data Confidentiality ............................................................................ 45 
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CHAPTER 13: REFERENCES ..................................................................................................................... 47 
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LIST OF ABBREVIATIONS 
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ABBREVIATION 
DEFINITION 
AP 
Artificial Pancreas 
BG 
Blood Glucose 
BT/BTLE 
Bluetooth, Bluetooth low energy 
CRF 
Case Report Form 
CGM 
Continuous Glucose Monitoring 
CLC 
Closed-Loop Control 
CSII 
Continuous Subcutaneous Insulin Injection 
CTR 
Control-to-Range 
DiAs 
Diabetes Assistant 
DKA 
Diabetic Ketoacidosis 
EC 
European Commission 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HbA1c 
Hemoglobin A1c 
HCL 
Hybrid Closed Loop 
ID 
Identification 
iDCL 
International Diabetes Closed Loop 
IDE 
Investigational Device Exemption 
IOB 
Insulin-on-Board 
IQR 
Interquartile Range 
JDRF 
Juvenile Diabetes Research Foundation 
NIH 
National Institutes of Health 
POC 
Point-of-Care 
QA 
Quality Assurance 
QC 
Quality Control 
RBM 
Risk-Based Monitoring 
SAP 
Sensor-Augmented Pump 
SD 
Standard Deviation 
TDI 
Total Daily Insulin 
UI 
User Interface 
 
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UNIVERSITY OF VIRGINIA 
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Signature Page 
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Safety and Efficacy of Initializing the Control-IQ Artificial 
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Pancreas System Using Total Daily Insulin  
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Protocol Identifying Number: Winter-Study-2019 
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IDE Sponsor: Marc Breton, PhD 
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Version Number: v1.4 
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2/7/2019 
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Protocol Chair/Director 
 
Name, degree 
Marc Breton, PhD 
Signature / Date 
 
 
 
 
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SITE PRINCIPAL INVESTIGATOR STATEMENT OF COMPLIANCE 
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Protocol Title: Safety and Efficacy of Initializing the Control-IQ Artificial Pancreas System 
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Using Total Daily Insulin 
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Protocol Version/Date: v1.4/07FEB2019 
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I have read the protocol specified above.  In my formal capacity as a Site Principal Investigator, 
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my duties include ensuring the safety of the study participants enrolled under my supervision 
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with complete and timely information, as outlined in the protocol.  It is understood that all 
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information pertaining to the study will be held strictly confidential and that this confidentiality 
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requirement applies to all study staff at this site. 
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This trial will be carried out in accordance with ICH E6 Good Clinical Practice (GCP) and as 
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required by the following: United States (US) Code of Federal Regulations (CFR) applicable to 
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clinical studies (45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 
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CFR Part 812). 
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As the Principal Investigator, I will assure that no deviation from, or changes to the protocol 
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will take place without prior agreement from the sponsor and documented approval from the 
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Institutional Review Board (IRB), or other approved Ethics Committee, except where necessary 
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to eliminate an immediate hazard(s) to the trial participants. 
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All key personnel (all individuals responsible for the design and conduct of this trial) have 
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completed Human Participants Protection Training and Good Clinical Practice Training.  
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Further, I agree to ensure that all staff members involved in the conduct of this study are 
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informed about their obligations in meeting the above commitments. 
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Investigator’s Signature __________________________________ Date: _____ / _____ / _____ 
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             dd     mmm 
yyyy 
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Investigator’s Name: _____________________________ 
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Site Name: _______________________________ 
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UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
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PROTOCOL SUMMARY 
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PARTICIPANT AREA 
DESCRIPTION 
Title 
Safety and Efficacy of Initializing the Control-IQ Artificial Pancreas 
System Using Total Daily Insulin 
Investigational Device 
Control-IQ Artificial Pancreas System with MyTDI 
Objectives 
The objective of the study is to assess the safety and efficacy of using the 
Control-IQ artificial pancreas system using MyTDI in a randomized 
controlled trial. 
Study Design 
Up to 25 participants may be consented.  Up to 20 participants will 
complete a 5-day at-home data collection period prior to coming to the 
Ski Admission where they will be randomized in a 1:1 fashion.  Half of 
participants will initiate on the Control-IQ AP with their usual parameters 
while half will be initiated on the Control-IQ with MyTDI AP system.  
Participants will continue study treatment for an additional 5 days at home 
following the end of the Ski Admission. 
Number of Sites 
1 
Endpoint 
The primary outcome for the first phase is time in target range 70-180 
mg/dL measured by CGM in Control-IQ group vs Control-IQ with 
MyTDI group over approximately 2 weeks. 
Population 
Key Exclusion Criteria  
- Age 12-18 
- Clinical diagnosis of Type 1 Diabetes 
Key Exclusion Criteria  
- History of DKA in the past 6 months 
- History of hypoglycemic seizure or loss of consciousness in the past 
6 months 
Sample Size 
20 participants (up to 25 may be consented) 
Treatment Groups 
Group 1 (HCL – Hybrid Closed Loop): 
• 
Control-IQ with usual parameters 
Group 2 (MyTDI): 
• 
Control-IQ with MyTDI 
Participant Duration 
3 weeks 
Protocol Overview/Synopsis 
After consent is signed, eligibility will be assessed.  Eligible participants 
will be screened and enter the data collection period for approximately 5 
days at home.  Participants will then be randomized 1:1 to the use of 
Control-IQ vs. Control-IQ with MyTDI during a 72 hours ski admission.  
Following the admission, participants will continue the randomized 
treatment for approximately 5 days at home. 
 
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UNIVERSITY OF VIRGINIA 
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Figure 1: Study Design 
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Following a 5-day at-home data collection period, participants will be randomized 1:1 to use the 
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Control-IQ system with their usual parameters or the Control-IQ system based on his/her total 
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daily insulin.  This treatment will continue through the Ski Admission and for 5 days at home.
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Table 1. Schedule of Study Visits and Procedures 
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Screening 
Post-Training 
Data 
Collection 
Ski Admission 
Post-Admission Data 
Collection 
End of 
Study 
Location 
Clinic 
Home 
Ski Lodge 
Home 
Home 
Comment 
Screen / Enroll 
5 Days 
72 Hours 
5 Days 
15-60 min 
Informed Consent 
X 
 
 
 
 
Eligibility Assessment 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
HbA1c  
X 
 
 
 
 
Randomization 
 
 
X 
 
 
Pregnancy test (if applicable) 
X 
 
X 
 
 
Physical Exam 
X 
 
X 
 
 
Vital Signs (including height/weight) 
X 
 
X 
 
 
Device Data download(s) 
 
 
X 
 
X 
Wear Study CGM, Insulin Pump, & Activity 
Tracker 
 
X 
X 
X 
 
Group 1:  - Control-IQ AP (usual parameters) 
 
 
X 
 
Group 2:  - Control-IQ AP with myTDI 
 
 
X 
 
Review diabetes management and AEs 
X 
X 
X 
X 
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UNIVERSITY OF VIRGINIA 
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Chapter 1: Background Information 
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1.1 Introduction 
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The Tandem t:slim X2 insulin pump with Control-IQ Technology is a third-generation closed-
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loop control (CLC) system.  The CLC is an “artificial pancreas” (AP) that uses algorithms to 
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automatically manage insulin delivery for people with diabetes based on their blood sugar and 
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calculated insulin needs.  This system retains the same control algorithm that was initially tested 
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by UVA’s DiAs system and then implemented in the inControl system. DiAs is described in 13 
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IDEs (see IDEs 1-12 and 14 in the list below) and inControl is described in IDEs G160097, 
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G160181, G150240, G140169/S010.  For complete algorithmic and clinical background, we 
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refer to these IDEs and to a number of scientific publications that describe glycemic control 
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outcomes and clinical impressions from the use of these systems (see list of peer-reviewed 
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papers in References).  This control algorithm has been implemented in two mobile platforms 
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(DiAs and inControl) and has been tested in over 30 clinical trials by hundreds of adults and 
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children with type 1 diabetes in the United States and overseas  
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This trial will expand on a number of clinical trials that have extensively tested the AP system in 
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over 350,000 hours of outpatient human use and in several centers in the U.S. and abroad.  The 
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italicized IDEs are currently using the t:slim X2 with Control-IQ Technology system proposed in 
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this trial: 
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1. IDE #G110095: Feasibility study of closed loop control in type 1 diabetes using heart rate 
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monitoring as an exercise marker, approved 10/08/2011;  
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2. IDE #G120032: Early feasibility (pilot) study of outpatient control-to-range; 3/2/2012;  
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3. IDE #G120210: Early feasibility study 2 of outpatient control-to-range; 10/12/2012;  
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4. IDE #G130118: DiAs control-to-range nocturnal closed-loop camp study; 6/19/2013;  
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5. IDE #G130121: Optimizing closed-loop control of type 1 diabetes mellitus in adolescents; 
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6/19/2013;  
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6. IDE# G130142: Closed loop control in adolescents using heart rate as exercise indicator; 
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7/16/13;  
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7. IDE #G130143: Early feasibility study of adaptive advisory/automated (AAA) control of type 
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1 diabetes; 7/19/2013;  
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8. IDE #G140066: Full day and night closed-loop with DiAs platform; 5/9/14.  
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9. IDE #G140068: Unified Safety System (USS) Virginia Closed Loop versus sensor augmented 
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pump therapy overnight in type 1 diabetes; 5/14/2014;  
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10. IDE #G140089: Outpatient control-to-range: Safety and efficacy with day-and-night in-home 
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use; 6/6/2014;  
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11. IDE #G140169: Unified Safety System (USS) Virginia Closed-Loop versus Sensor 
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Augmented Pump (SAP) therapy for hypoglycemia reduction in type 1 diabetes; 10/3/2014.  
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12. IDE #G150221: Reducing risks and improving glucose control during extended exercise in 
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youth with T1DM: The AP Ski Camp; 11/09/2015;  
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13. IDE #G150240: Project Nightlight: Efficacy and system acceptance of dinner/night vs. 24 hr 
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closed loop control; 11/12/2015;  
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14. IDE #G160047: Closed-loop in young children 5-8 years old using DiAs platform; 
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03/29/2016; 
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15. IDE #G160097: Clinical Acceptance of the Artificial Pancreas: the International Diabetes 
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Closed-Loop (iDCL) Trial/Research Site Training Protocol; 06/03/16.  
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16. IDE#G160181: PROTOCOL 1 for “Clinical Acceptance of the Artificial Pancreas: The 
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International Diabetes Closed Loop (iDCL) Trial; 09/21/16  
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17. IDE#G170255: Protocol 3 for “Pilot Trial of t:slim X2 with Control-IQ Technology”; 
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11/16/17 and IDE#G170255/S001 Protocol 3 for “Training Study of t:slim X2 with Control-IQ 
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Technology”; 11/16/17 
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18. IDE#G160181: Real-Time Monitoring and Glucose Control During Winter-Sport Exercise in 
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Youth with Type 1 Diabetes: The AP Ski Camp Continued; 10/26/2017 
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19. IDE#150240/S008: A long-term home use study, enrolling 18-70 years old TID participants 
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since January 2018; this study is expected to be completed April 2019; 02/02/18; 
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20. IDE#G18053 : “The International Diabetes Closed Loop (iDCL) trial: Clinical Acceptance 
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of the Artificial Pancreas - A Pivotal Study of t:slim X2 with Control-IQ Technology”; 
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randomized controlled trial of 6 month at home closed loop system vs. sensor-augmented pump 
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with a 3 month extension phase ; 04/13/18 ; 
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21. IDE #G180174: “The VRIF Trial: Hypoglycemia Reduction with Automated-Insulin Delivery 
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System”; 08/29/18.  
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22. IDE#G180053/S007 :“The International Diabetes Closed Loop (iDCL) trial: Clinical 
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Acceptance of the Artificial Pancreas - A Pivotal Study of t:slim X2 with Control-IQ Technology 
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– Extension Study ;”A 3-month extension study for participants who completed the prior 6-
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month randomized controlled trial (RCT) of a closed loop system (Control-IQ) vs. sensor-
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augmented pump (SAP); [PENDING REVIEW BY AGENCY] 
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23. IDE#G180053/S008 : “The International Diabetes Closed Loop (iDCL) Trial: Clinical 
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Acceptance of the Artificial Pancreas in Pediatrics - A Pivotal Study of t:slim X2 with Control-
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IQ Technology”;  4-month parallel group randomized clinical trial with 3:1 randomization to 
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intervention with the closed loop system vs. standard of care (SC); [PENDING REVIEW BY 
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AGENCY] 
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This trial will test the closed-loop AP system both under home conditions as well as during a 
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stress situation of ski camp while utilizing a new feature, MyTDI, which will be described in 
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more detail in the next section. 
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1.2 Rationale 
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The closed-loop AP system works by modulating subcutaneous insulin infusion based on 
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computed real-time needs.  Studies have shown that use of an AP system results in increased 
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time in the euglycemic range (70-180 mg/dL), particularly overnight.  Challenges persist during 
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times of rapid blood sugar fluctuations, such as following meals or during exercise.  Significantly 
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improved glycemic control and fewer hypoglycemic events have been previously demonstrated 
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in pediatric patients using the AP system in summer and winter camp settings.  Studies to date 
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have run the system using the foundation of the subject’s home insulin parameters, which are 
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often complicated and involve fluctuating basal rates, carbohydrate ratios, and correction factors 
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depending on the time of the day and might not be reflective of his/her true insulin needs. The 
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CLC system allows the user to receive feedback on his/her average total daily insulin needs with 
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a report of Total Daily Insulin (TDI). Clinicians can in turn use TDI to easily determine insulin 
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pump parameters using standard formulas to calculate the optimal basal rate, carbohydrate ratio, 
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and correction factor as follows:  
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• Basal rate = TDI/48 (half of the daily insulin needs are delivered in the form of basal 
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insulin) 
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• Correction factor (CF) = 1650/TDI  
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• Carb ratio (CR) = 450/TDI (to be used for lunch and dinner)  
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• Carb ratio for breakfast: to achieve a 20% increase in insulin we will use the following 
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carb ratio: CRbkfst=CR/1.2  (to account for increased insulin needs in the morning)  
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The system can then modify the insulin to keep blood glucose in range as necessary.  
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This trial aims to demonstrate the safety and feasibility of using MyTDI to determine insulin 
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parameters on the CLC AP system t:slim X2 with Control-IQ technology for use both at ski 
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camp and at home in adolescent patients with type 1 diabetes.    
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Primary Specific Aim: 
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To assess the safety and feasibility of using insulin parameters as determined by MyTDI during 
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normal outpatient conditions in the t:slim X2 with Control-IQ Technology AP system.  
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Secondary Specific Aims: 
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To assess the safety and feasibility of using insulin parameters as determined by MyTDI during 
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intense exercise outpatient conditions in the t:slim X2 with Control-IQ Technology AP system.  
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1.3 Potential Risks and Benefits of the Investigational Device 
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Risks and Benefits are detailed below. Loss of confidentiality is a potential risk; however, data 
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are handled to minimize this risk.  Hypoglycemia, hyperglycemia and ketone formation are 
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always a risk in participants with type 1 diabetes and participants will be monitored for this. 
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1.3.1 Known Potential Risks 
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1.3.1.1 Venipuncture Risks 
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A hollow needle/plastic tube will be placed in the arm for taking blood samples. Blood draws 
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can cause some common reactions like pain, bruising, or redness at the sampling site.  Less 
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common reactions include bleeding from the sampling site, formation of a small blood clot or 
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swelling of the vein and surrounding tissues, and fainting. 
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1.3.1.2 Fingerstick Risks 
311 
About 1 drop of blood will be removed by fingerstick for measuring blood sugars and sometimes 
312 
HbA1c or other tests. This is a standard method used to obtain blood for routine hospital 
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laboratory tests.  Pain is common at the time of lancing.  In about 1 in 10 cases, a small amount 
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of bleeding under the skin will produce a bruise.  A small scar may persist for several weeks.  
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The risk of local infection is less than 1 in 1000.  This should not be a significant contributor to 
316 
risks in this study as fingersticks are part of the usual care for people with diabetes. 
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1.3.1.3 Subcutaneous Catheter Risks (CGM) 
318 
Participants using the CGM will be at low risk for developing a local skin infection at the site of 
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the sensor needle placement.  If a catheter is left under the skin for more than 24 hours, it is 
320 
possible to get an infection where it goes into the skin, with swelling, redness and pain.  There 
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may be bleeding where the catheter is put in and bleeding under the skin causes a bruise (1 in 10 
322 
risk). 
323 
Study staff should verbally alert the participant that on rare occasions, the CGM may break and 
324 
leave a small portion of the sensor under the skin that may cause redness, swelling or pain at the 
325 
insertion site.  The participant should be further instructed to notify the study coordinator 
326 
immediately if this occurs. 
327 
1.3.1.4 Risk of Hypoglycemia 
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As with any person having type 1 diabetes and using insulin, there is always a risk of having a 
329 
low blood sugar (hypoglycemia).  The frequency of hypoglycemia should be no more and 
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possibly less than it would be as part of daily living.  Symptoms of hypoglycemia can include 
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sweating, jitteriness, and not feeling well.  Just as at home, there is the possibility of fainting or 
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seizures (convulsions) and that for a few days the participant may not be as aware of symptoms 
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of hypoglycemia.  A CGM functioning poorly and significantly over-reading glucose values 
334 
could lead to inappropriate insulin delivery. 
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1.3.1.5 Risk of Hyperglycemia 
336 
Hyperglycemia and ketonemia could occur if insulin delivery is attenuated or suspended for an 
337 
extended period or if the pump or infusion set is not working properly.  A CGM functioning 
338 
poorly and significantly under-reading glucose values could lead to inappropriate suspension of 
339 
insulin delivery. 
340 

UNIVERSITY OF VIRGINIA 
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1.3.1.6 Risk of Device Reuse 
341 
The study CGM system is labeled for single use only. The sensor (the component of the system 
342 
that enters the skin) will be single use only. The transmitter and receiver may be reused during 
343 
the study after cleaning the device using a hospital-approved cleaning procedure. The transmitter 
344 
is attached to the sensor but does not enter the skin and the receiver is a handheld device. 
345 
Participants will be informed that FDA or relevant national authorities have approved these 
346 
devices for single use and that by using them among multiple patients, bloodborne pathogens 
347 
(i.e. Hepatitis B) may be spread through the use of multiple users. 
348 
The study insulin pump is labeled for single-patient use. During the study, this device may be 
349 
reused after cleaning adhering to a hospital-approved cleaning procedure. All infusion set 
350 
equipment will be single patient use only (infusion set insertion kits, tubing, cartridges etc.)  
351 
Participants will be informed that FDA or relevant national authorities typically approve the 
352 
insulin pump device for single use and that by using them among multiple patients, bloodborne 
353 
pathogens (i.e. Hepatitis B) may be spread through the use of multiple users. 
354 
The study blood glucose meter and blood ketone meter are labeled for single-patient use. 
355 
During the study, only one person can use each device as there are rare risks that bloodborne 
356 
pathogens (i.e. Hepatitis B) may be spread through the use of multiple users. 
357 
1.3.1.7 Risk of Injury during Ski/Snowboarding 
358 
Bruising, dislocations, sprains, and fractures of the leg and shoulders are very common while 
359 
participating in these activities.  
360 
1.3.1.8 Other Risks 
361 
Some participants may develop skin irritation or allergic reactions to the adhesives used to secure 
362 
the CGM, or to secure the insulin infusion sets for the continuous subcutaneous insulin infusion.  
363 
If these reactions occur, different adhesives or “under-taping” (such as with IV 3000, Tegaderm, 
364 
etc.) will be tried, sites will be rotated frequently, and a mild topical steroid cream or other 
365 
medication may be required. 
366 
Whenever the skin is broken there is the possibility of an infection.  The CGM and pump 
367 
infusion sites are inserted under the skin.  It is possible that any part that is inserted under the 
368 
skin may cause an infection.  These occur very infrequently, but, if an infection was to occur, 
369 
oral and/or topical antibiotics can be used.  The risk of skin problems could be greater if you use 
370 
a sensor for longer than it is supposed to be used.  Therefore, participants will be carefully 
371 
instructed about proper use of the sensor. 
372 
Data downloaded from the CGM, pump, and the home glucose and ketone meter will be 
373 
collected for the study as measures of diabetes self-management behaviors.  Some people 
374 
may be uncomfortable with the researchers' having such detailed information about their daily 
375 
diabetes habits. 
376 
1.3.2 Known Potential Benefits 
377 
One purpose of this research is to reduce the frequency of hypoglycemia and severe 
378 
hypoglycemic events in relation to performing a winter sport exercise (skiing/snowboarding). 
379 

UNIVERSITY OF VIRGINIA 
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Hypoglycemia is the number one fear of many individuals and families with someone who has 
380 
type 1 diabetes and this fear often prevents optimal glycemic control. 
381 
It is expected that this protocol will yield increased knowledge about using an automated 
382 
closed-loop to control the glucose level. The individual participant may not benefit from study 
383 
participation. 
384 
1.4 General Considerations 
385 
The study is being conducted in compliance with the policies described in the study policies 
386 
document, with the ethical principles that have their origin in the Declaration of Helsinki, with 
387 
the protocol described herein, and with the standards of Good Clinical Practice (GCP). 
388 
Whenever possible, data will be directly collected in electronic case report forms, which will be 
389 
considered the source data. 
390 
There is no restriction on the number of participants to be enrolled by each site toward the 
391 
overall recruitment goal. 
392 
The protocol is considered a significant risk device study, due to the fact that the closed loop 
393 
system is experimental.  Therefore, an investigational device exemption (IDE) from the U.S. 
394 
Food and Drug Administration (FDA) is required to conduct the study. 
395 

UNIVERSITY OF VIRGINIA 
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Page 19 of 48 
Chapter 2: Study Enrollment and Screening 
396 
2.1 Participant Recruitment and Enrollment 
397 
Enrollment will proceed with the goal of having 20 participants, age 12-18 years, enter the 
398 
randomized trial, with the expectation that 20 participants will complete the randomized trial.  A 
399 
maximum of 25 individuals may be enrolled into screening for the study in order to achieve this 
400 
goal. 
401 
Participants will be recruited at the University of Virginia. 
402 
2.1.1 Informed Consent and Authorization Procedures 
403 
Potential eligibility may be assessed as part of a routine-care examination.  Before completing 
404 
any procedures or collecting any data that are not part of usual care, written informed consent 
405 
will be obtained. 
406 
For potential study participants ≥18 years old, the study protocol will be discussed with the 
407 
potential study participant by study staff.  The potential study participant will be given the 
408 
Informed Consent Form to read.  Potential study participants will be encouraged to discuss the 
409 
study with family members and their personal physicians(s) before deciding whether to 
410 
participate in the study. 
411 
For potential participants under 18 years of age, a parent/legal guardian (referred to subsequently 
412 
as “parent”) will be provided with the Informed Consent Form to read and will be given the 
413 
opportunity to ask questions.  Potential participants meeting the IRB’s minimum age of assent 
414 
will be given a Child Assent Form to read and discuss with his/her parents and study personnel.  
415 
If the parent and child agree to participate, the Informed Consent Form and Child Assent Form 
416 
will be signed.  A copy of the consent form will be provided to the participant and his/her parent 
417 
and another copy will be added to the participant’s study record. 
418 
A participant is considered enrolled when the informed consent form has been signed. 
419 
2.2 Participant Inclusion Criteria 
420 
Individuals must meet all of the following inclusion criteria in order to be eligible to participate 
421 
in the study. 
422 
• Criteria for documented hyperglycemia (at least 1 must be met): 
423 
o Clinical diagnosis of type 1 diabetes (C-peptide levels and antibody 
424 
determinations are not required) 
425 
o Diagnosis of type 1 diabetes is based on the investigator’s judgement 
426 
• Criteria for requiring insulin at diagnosis (both criteria must be met): 
427 
o Daily insulin therapy for ≥ 6 months 
428 
o Insulin pump therapy for ≥ 3 months 
429 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 20 of 48 
• Age 12-18 years 
430 
• Currently using no insulins other than one of the following rapid-acting insulins at the 
431 
time of enrollment: insulin lispro (Humalog), insulin aspart (Novolog), or insulin 
432 
glulisine (Apidra). If using glulisine, subject must be willing to switch to lispro or aspart. 
433 
• Treatment with any non-insulin glucose-lowering agent (including GLP-1 agonists, 
434 
Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, biguanides, sulfonylureas, and 
435 
naturaceuticals) is permitted if stable on current dose for at least 3 months. 
436 
• Willingness to wear a continuous glucose sensor and physiological monitor for the 
437 
duration of the study. 
438 
• For females, not pregnant or breastfeeding.  Female subjects who are sexually active 
439 
should agree to use birth control during the study. 
440 
2.3 Participant Exclusion Criteria 
441 
Individuals meeting any of the following exclusion criteria at baseline will be excluded from 
442 
study participation. 
443 
• Diabetic ketoacidosis in the past 6 months 
444 
• Hypoglycemic seizure or loss of consciousness in the past 6 months 
445 
• History of seizure disorder 
446 
• History of any heart disease including coronary artery disease, heart failure, or 
447 
arrhythmias 
448 
• History of altitude sickness 
449 
• Chronic pulmonary conditions that could impair oxygenation 
450 
• Cystic fibrosis 
451 
• Current use of oral glucocorticoids, beta-blockers or other medications, which in the 
452 
judgement of the investigator, would be a contraindication to participation in the study. 
453 
• History of ongoing renal disease (other than microalbuminuria). 
454 
• Subjects requiring intermediate or long-acting insulin (such as NPH, Detemir, or 
455 
Glargine). 
456 
• Pregnancy 
457 
• Presence of a febrile illness within 24 hours of the Ski Admission. 
458 

UNIVERSITY OF VIRGINIA 
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Page 21 of 48 
• Medical or psychiatric conditions that in the judgement of the investigator might interfere 
459 
with the completion of the protocol such as: 
460 
o Inpatient psychiatric treatment in the past 6 months 
461 
o Uncontrolled adrenal insufficiency 
462 
o Alcohol abuse 
463 
2.4 Screening Procedures 
464 
After informed consent has been signed, a potential participant will be evaluated for study 
465 
eligibility through the elicitation of a medical history, performance of a physical examination 
466 
by study personnel (i.e. licensed medical physicians and nurse practitioners) and local laboratory 
467 
testing if needed to screen for exclusionary medical conditions. 
468 
Individuals who do not initially meet study eligibility requirements may be rescreened at a later 
469 
date per investigator discretion. 
470 
2.4.1 Eligibility and Baseline Procedures at Screening 
471 
The following procedures and testing will be performed to ensure eligibility: 
472 
• Inclusion and exclusion criteria assessed 
473 
• Demographics (date of birth, sex, race and ethnicity) 
474 
• Contact information  
475 
• Medical history 
476 
• Concomitant medications and supplements 
477 
• Pregnancy Test for women of child-bearing potential (urine) 
478 
• Blood draw 
479 
• Hemoglobin A1c measured using the DCA2000 or comparable point of care device or local 
480 
lab; a lab result within 3 months of enrollment may be used at the investigator’s discretion 
481 
• Physical examination including height, weight, and vital signs (physical exam from the last 
482 
12 months may be used at the investigator’s discretion) 
483 

UNIVERSITY OF VIRGINIA 
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Page 22 of 48 
Chapter 3: Study System Training 
484 
3.1 Study Equipment Training 
485 
This phase may begin immediately after enrollment is complete.  Participants will be trained and 
486 
begin using the Control-IQ system to manage their glucose levels and insulin delivery at the 
487 
conclusion of the training session.  Participants will discontinue the use of their existing CGM 
488 
and insulin pump, if applicable.  Training on use of the activity tracker (i.e. Fitbit) will also 
489 
occur.  Participants will use the study equipment (study insulin pump, study CGM, study activity 
490 
tracker) to collect data for approximately 5 days prior to the Ski Admission. During this at-home 
491 
portion of the study, participants will be remotely monitored by at least one of their parents or 
492 
care providers, using the Dexcom or Tandem app. 
493 
3.1.1 Initiation of CGM 
494 
The participant will be provided with sensors and instructed to use the study CGM on a daily 
495 
basis. Training will be provided to participants not experienced with CGM use as to how to use 
496 
the CGM in real-time to make management decisions and how to review the data after an upload 
497 
for retrospective review. Participants using a personal CGM prior to the study will discontinue 
498 
the personal CGM beginning in this period. 
499 
The participant will be observed placing the sensor. The study CGM user’s guide will be 
500 
provided for the participant to take home. 
501 
3.1.2 Initiation of Study Pump 
502 
Participants will complete training on the study pump as detailed below. 
503 
• The participant will be fully instructed on the study insulin pump. A qualified system trainer 
504 
(i.e. Certified Diabetes Educator) will conduct the training and in particular discuss 
505 
differences from their home pump in important aspects such as calculation of insulin on 
506 
board and correction boluses. Additional topics are not limited to but may include: infusion 
507 
site initiation, cartridge/priming procedures, setting up the pump, charging the pump, 
508 
navigation through menus, bolus procedures including stopping a bolus, etc. 
509 
• The study team will assist the participant in study pump infusion site initiation and will start 
510 
the participant on the study pump. The study pump will be programmed with the 
511 
participant’s usual basal rates and pump parameters. The participant’s personal pump will be 
512 
removed. 
513 
• The participant will be supervised with the study pump during at least one meal or snack 
514 
bolus to ensure participant understanding of the pump features. 
515 
• The participant will be encouraged to review the literature provided with the pump and 
516 
infusion sets after the training is completed. 
517 
3.1.3 Initiation of Activity Tracker 
518 
Participants will receive a commercially available activity tracker to collect additional 
519 
information about movement and heart rate.  The activity tracker can be removed during bathing. 
520 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 23 of 48 
 
521 
3.1.4 Blood Glucose and Ketone Testing 
522 
Participants will receive supplies for blood glucose and ketone testing. 
523 
• Blood glucose testing 
524 
 Participants will be provided with a study blood glucose meter and test strips. 
525 
 All study blood glucose meters will be QC tested with at least two different 
526 
concentrations of control solution if available during all office visits.  A tested meter 
527 
will not be used in a study if it does not read within the target range at each 
528 
concentration per manufacturer labeling.   
529 
 Participants will be reminded to use the study blood glucose meter for all fingerstick 
530 
BGs during the study. 
531 
 Participants will be given guidelines for treatment of low or high blood glucose. 
532 
• Blood ketone testing 
533 
 Participants will be provided with a study blood ketone meter and test strips. 
534 
 All study blood ketone meters will be QC tested with at least two different 
535 
concentrations of control solution if available during all office visits.  A tested meter 
536 
will not be used in a study if it does not read within the target range at each 
537 
concentration per manufacturer labeling.     
538 
 Participants will be instructed to perform blood ketone testing as described in 
539 
section 6.2.4 
540 
 Participants will be given guidelines for treatment of elevated blood ketones 
541 
• Participants will be required to have a home glucagon emergency kit. Participants who 
542 
currently do not have one will be given a prescription for the glucagon emergency kit 
543 
3.1.5 Post-Training Check In 
544 
The study team will contact the participants approximately 48-72 hours after initiation of the 
545 
study equipment to discuss: 
546 
• Questions or concerns about the study and/or equipment 
547 
• Ensure proper use of study equipment 
548 
• Ask about the occurrence of any events, including adverse events   
549 
Members of the study team are available 24 hours a day to address questions or concerns from 
550 
the participants.  Participants will have the contact information of multiple team members.  If 
551 
there is a medical emergency that requires immediate medical attention, participants will be 
552 
instructed to call emergency medical services (e.g. 911).   
553 
 
 
554 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 24 of 48 
 
555 
Chapter 4: Ski Admission Procedures 
556 
4.1 Admission Check-In Procedures 
557 
4.1.1 Participant Check-In & Verification 
558 
At time of check-in, participants will undergo the following procedures/tests: 
559 
• Vital signs measured 
560 
• A fever or had a significant illness within 24-hours of admission will disqualify 
561 
participant from study 
562 
• A fingerstick blood glucose and fingerstick ketone measurement will be obtained 
563 
• Female subjects of childbearing potential will be required to complete a urine pregnancy 
564 
test. If positive, participant will be discontinued from the study.  
565 
• Study devices and insertion sites will be inspected 
566 
• Confirm that the participant brought his/her personal insulin, study supplies, and regular 
567 
medications.   
568 
• Participants will be asked to perform a blood ketone fingerstick.  If ketones >1.5 mmol/L, 
569 
study staff should treat with oral hydration and, if needed, the Glycemic Treatment 
570 
Guidelines will be followed; ketones will be re-checked every hour until ≤1.5 mmol/L.  
571 
The participant will be able to begin participation in the winter sport activities once the 
572 
CGM reads between 80-300 mg/dL and ketones are ≤1.5 mmol/L. 
573 
• Data from the participant’s insulin pumps will be reviewed and/or downloaded for a 
574 
review of pump settings and average of daily insulin delivery. 
575 
4.1.2 Randomization 
576 
After participants have successfully checked in and are deemed eligible to continue participation 
577 
in the study, they may be randomized.  Using a randomized block design, the participants will be 
578 
assessed and put in blocks of two according to age and HbA1c.  If an identical match is not 
579 
possible, the closest in age and HbA1c value will be paired and then randomized – one member 
580 
of each block randomly assigned to each of the two treatment groups. 
581 
Participants who randomize to Group 1 Hybrid Closed Loop (HCL) will have no modifications 
582 
to their insulin pump parameters other than the standard 20% reduction in insulin to account for 
583 
increased exercise while at ski camp.  Participants who randomize to Group 2 (MyTDI) will have 
584 
modifications to their insulin pump parameters to take into consideration his/her total daily 
585 
insulin along with the 20% reduction in insulin during ski camp.   
586 
The MyTDI adjustments will be as follows: 
587 
• A single basal rate equal to TDI/48 will be implemented across the whole day 
588 
• A single correction factor of 1650/TDI will be implemented across the whole day 
589 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 25 of 48 
• Carbohydrate ratios will be set at: 
590 
o 0000-04:00 
CR=450/TDI 
591 
o 0400-1100 
CR=450/TDI)/1.2 
592 
o 1100-0000 
CR=450/TDI 
593 
TDI will be reduced by 20% of the internal Control-IQ estimation total daily dose; if not 
594 
available, total daily dose over the last 5 days will be used. 
595 
Aside from the insulin pump settings, all other study procedures are identical in the two 
596 
treatment groups during the Admission and the second at-home portion of the study. 
597 
4.2 Main Admission Activities and Procedures 
598 
4.2.1 General Admission Overview 
599 
During the entire admission, participants will be monitored remotely by the study team.  Study 
600 
team members trained in all protocol interventions (including the hypo and hyperglycemia safety 
601 
protocols) will be skiing with the participants, with each member remotely connected to the 
602 
participants CGM data.  In addition, a study team member trained in all protocol and glycemic 
603 
treatment guidelines procedures will be available at a central location in the resort.   
604 
All recreational activities will be managed by ‘Riding on Insulin’ with study staff supervision. 
605 
During the overnight hours, study staff will be actively monitoring real-time CGM data for all 
606 
participants from a dedicated room in the ski resort with direct access to the participants. 
607 
4.2.2 Device Procedures for the Participants 
608 
All participants will continue to wear the CGM and insulin pump that was provided to them at 
609 
the Screening Visit throughout the Admission, with the only difference between the randomized 
610 
groups being the insulin regimen settings in the AP system.   
611 
Participants will have all equipment with them at all times, including a cell phone (personal or 
612 
study-provided) with the Dexcom Follow App.  Participants will be asked to respond to both 
613 
hypoglycemia and hyperglycemia alarms.  If they do not respond to the alarms within 10 
614 
minutes, study personnel will assist the subject as per the Glycemic Treatment Guidelines.  
615 
Participants may be re-educated as needed by the study staff, who will be available at all times to 
616 
assure proper use of all study equipment. 
617 
4.2.3 Participants’ Admission Itinerary 
618 
Participants will generally follow the below schedule during the Admission: 
619 
Evening of Check-in 
620 
1500-1900: Check-In & Randomization.  Participants will undergo the check-in procedures 
621 
outlined in section 4.1.  Study team will download the study equipment. 
622 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 26 of 48 
1900-2000: Dinner.  The study CGM will be used to determine the pre-meal bolus. 
623 
2000-2300: Evening Activity. 
624 
Day 1 
625 
0800-0900: Breakfast.  The study CGM will be used to determine the pre-meal bolus. 
626 
0900-1200: Morning Ski Activity.  Participants will begin the morning ski session if his/her 
627 
CGM reads >100 mg/dL.  If ≤ 100 mg/dL, the Glycemic Treatment Guidelines will be followed 
628 
until cleared to begin activity. 
629 
1200-1300: Lunch.  The study CGM will be used to determine the pre-meal bolus. 
630 
1300-1600: Afternoon Ski Activity.  Participants will begin the afternoon ski session if his/her 
631 
CGM reads >100 mg/dL.  If ≤ 100 mg/dL, the Glycemic Treatment Guidelines will be followed 
632 
until cleared to begin activity. 
633 
1600-1800: Quiet time 
634 
1800-2000: Dinner.  The study CGM will be used to determine the pre-meal bolus. 
635 
2200: Bedtime Snack.  The study CGM will be used to determine the pre-meal bolus. 
636 
2030-2300: Evening Activity.   
637 
Day 2 
638 
0800-0900: Breakfast.  The study CGM will be used to determine the pre-meal bolus. 
639 
0900-1200: Morning Ski Activity.  Participants will begin the morning ski session if his/her 
640 
CGM reads >100 mg/dL.  If ≤ 100 mg/dL, the Glycemic Treatment Guidelines will be followed 
641 
until cleared to begin activity. 
642 
1200-1300: Lunch.  The study CGM will be used to determine the pre-meal bolus. 
643 
1300-1600: Afternoon Ski Activity.  Participants will begin the afternoon ski session if his/her 
644 
CGM reads >100 mg/dL.  If ≤ 100 mg/dL, the Glycemic Treatment Guidelines will be followed 
645 
until cleared to begin activity. 
646 
1600-1800: Quiet time 
647 
1800-2000: Dinner.  The study CGM will be used to determine the pre-meal bolus. 
648 
2200: Bedtime Snack.  The study CGM will be used to determine the pre-meal bolus. 
649 
2030-2300: Evening Activity.   
650 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 27 of 48 
Day 3 
651 
0800-0900: Breakfast.  The study CGM will be used to determine the pre-meal bolus. 
652 
0900-1200: Checkout and discharge to parents. The study staff will adjust all participants’ 
653 
insulin pumps to remove the 20% rate reduction with the cessation of ski activity and in 
654 
anticipation of the at-home treatment period.  Participants will be discharged if appropriate and 
655 
in accordance with the Glycemic Treatment Guidelines.  Participants will be discharged with the 
656 
study equipment and any supplies needed for the at-home treatment period.  
657 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 28 of 48 
Chapter 5: At-Home Treatment & Study Completion 
658 
5.1 At-Home Treatment Continuation 
659 
Participants discharged from the Ski Admission will continue the randomized treatment for 
660 
approximately 5 days at home.  Participants are free to engage in their normal daily activities and 
661 
diets during this time.  Participants will receive and be instructed to follow the Glycemic 
662 
Treatment Guidelines during this time.  During the at-home continuation portion of the study, 
663 
participants will be remotely monitored by at least one of their parents or care providers, using 
664 
the Dexcom or Tandem app.   
665 
5.1.1 Post Admission Follow-up Phone Call 
666 
The study team will contact the participants approximately 24-48 hours after they are discharged 
667 
from the Ski Admission to discuss: 
668 
• Questions or concerns about the study and/or equipment 
669 
• Ensure proper use of study equipment 
670 
• Ask about the occurrence of any events, including adverse events   
671 
Members of the study team are available 24 hours a day to address questions or concerns from 
672 
the participants.  Participants will have the contact information of multiple team members.  If 
673 
there is a medical emergency that requires immediate medical attention, participants will be 
674 
instructed to call emergency medical services (e.g. 911).   
675 
5.2 Final Study Visit 
676 
The final study visit may be performed remotely (phone) or in-person.  After approximately 5 
677 
days of at-home use of the study-assigned treatment, participants will be instructed to turn off the 
678 
Control-IQ system and remove the study equipment.  If this visit is performed in person, the 
679 
participant will return the study equipment to the study team.  If this visit is performed remotely, 
680 
the participant will return the study equipment by mailing it.  At this visit, participants will be 
681 
asked about any existing adverse events and any new adverse events that have not been reported 
682 
to the study team.   
683 
5.3 Early Termination Visit (If Applicable) 
684 
Participants will be asked to come for an end of study visit in the event of withdrawal or early 
685 
termination. 
686 
5.4 Unscheduled Visits 
687 
Participants may have unscheduled visits during the study period if required for additional device 
688 
training or other unanticipated needs per the study investigator discretion. 
689 
5.5 Participant Access to Study Device at Study Closure 
690 
Participant will return all investigational study devices and supplies (insulin pump, CGM, 
691 
activity tracker, and related supplies) at study closure.  Participant may keep the study ketone 
692 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 29 of 48 
meter and study glucometer if these devices are not marked for investigational use only after the 
693 
study team has downloaded all data from the devices. 
694 
 
 
695 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 30 of 48 
Chapter 6: Study Devices 
696 
6.1 Description of the Investigational Device 
697 
6.1.1 Insulin Pump 
698 
The study system will include the Tandem t:slim X2 with Control-IQ Technology.   
699 
6.1.2 Continuous Glucose Monitoring 
700 
The study CGM will include Dexcom G6 transmitter and sensors when using the Tandem t:slim 
701 
X2 with Control-IQ technology.  The CGM sensor will be replaced at least once every 10 days. 
702 
6.1.3 Blood Glucose Meter and Strips 
703 
Blood glucose levels will be measured using the study’s blood glucose meter (glucometer) and 
704 
the CGM device will be calibrated if needed using the study glucometer and strips in accordance 
705 
with the manufacturer’s labeling. 
706 
6.1.3.1 Blood Glucose Meter Testing 
707 
• All study blood glucose meters will be QC tested with at least two different concentrations of 
708 
control solution if available during all office visits.  A tested meter will not be used in a study 
709 
if it does not read within the target range at each concentration per manufacturer labeling.   
710 
• Participants will be reminded to use the study blood glucose meter for all fingerstick blood 
711 
glucose measurements. 
712 
6.1.3.2 Blood Glucose Meter Supplies 
713 
• Participants will be provided all necessary supplies during the study.   
714 
• Participants will permitted to keep these devices at the conclusion of the study. 
715 
6.1.4 Blood Ketone Meter and Strips 
716 
Blood ketone levels will be measured using the Abbott Precision Xtra Ketone Meter and strips in 
717 
accordance with the manufacturer’s labeling.  The blood glucose meter component of the 
718 
Precision Xtra device will not be used. 
719 
6.1.4.1 Blood Ketone Testing 
720 
• All study blood ketone meters will be QC tested with at least two different concentrations of 
721 
control solution if available during all office visits.  A tested meter will not be used in a study 
722 
if it does not read within the target range at each concentration per manufacturer labeling.   
723 
• Participants will be instructed on how to perform blood ketone testing. 
724 
• Participants will be given guidelines for treatment of elevated blood ketones. 
725 
6.1.4.2 Blood Ketone Meter Supplies 
726 
• Participants will be provided all necessary supplies during the study.   
727 
• Participants will permitted to keep these devices at the conclusion of the study.  
728 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 31 of 48 
6.1.5 Activity Tracker 
729 
• Participants will be trained on the study activity tracker that will be used to collect additional 
730 
information about movement and heart rate.  
731 
• Participants will be asked to wear the device during the entire study. The monitor can be 
732 
removed during bathing. 
733 
6.1.6 Study Device Accountability Procedures 
734 
Device accountability procedures will be detailed in the site procedures manual. 
735 
6.1.7 Blood Ketone Testing 
736 
• All study blood ketone meters will be QC tested with at least two different concentrations of 
737 
control solution if available during all office visits.  A tested meter will not be used in a study 
738 
if it does not read within the target range at each concentration per manufacturer labeling.   
739 
• Participants will be instructed on how to perform blood ketone testing. 
740 
• Participants will be given guidelines for treatment of elevated blood ketones. 
741 
6.2 Safety Measures 
742 
6.2.1 CGM Calibration 
743 
Throughout the study, participants will be instructed to calibrate the study CGM in accordance 
744 
with manufacturer labelling. 
745 
6.2.2 System Failure 
746 
If the CGM signal becomes unavailable for more than 20 minutes consecutively, Control-IQ or 
747 
closed loop will not operate to automatically adjust insulin. If the CGM is not connected, the 
748 
system will revert to usual function of the pump and deliver insulin with the insulin dosing 
749 
parameters programmed in the system for that individual. Resumption of Closed-Loop will 
750 
occur automatically once CGM signal is available again. 
751 
If the study system is unable to activate Control-IQ for any reason, the pump will automatically 
752 
revert to preprogrammed basal insulin delivery without any need for instruction from the user. 
753 
If the t:slim X2 detects a system error that does not allow the pump to operate, the Malfunction 
754 
Alarm will display and the participant will be instructed to contact Tandem Technical Support 
755 
via the study team. 
756 
6.2.3 Hypoglycemia Threshold Alert and Safety Protocol 
757 
During the course of the study, participants will be permitted to change the CGM low glucose 
758 
threshold alert setting on their device or mobile app, but will be instructed to choose a value no 
759 
less than 60 mg/dL. 
760 
The t:slim X2 with Control-IQ system will issue a predictive hypoglycemia alert (Control-IQ 
761 
Low Alert) when the system predicts BG <70 mg/dL within the next 15 minutes (<80 mg/dL 
762 
when exercise mode is activated). 
763 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 32 of 48 
If the participant receives a Control-IQ Low Alert, a message appears on the UI that is 
764 
accompanied by vibration followed by vibrations and/or sound if not acknowledged by the user 
765 
in 5 minutes.  This alert remains on the screen until acknowledged by the user. The user is 
766 
prompted to test blood sugar and treat with carbs. 
767 
If a participant’s CGM reading is <80 mg/dL, the Glycemic Treatment Guidelines will be 
768 
followed. 
769 
6.2.4 Hyperglycemia Threshold Alert and Safety Protocol 
770 
During the course of the study, participants will be permitted to change the CGM high glucose 
771 
threshold alert setting on their device or mobile app, but will be instructed to choose a value no 
772 
greater than 300 mg/dL. 
773 
The t:slim X2 with Control-IQ system will issue a predictive hyperglycemia alert (Control-IQ 
774 
High Alert) when the system has increased insulin delivery, but detects a CGM value above 200 
775 
mg/dL and does not predict the value will decrease in the next 30 minutes. 
776 
If the participant receives a Control-IQ High Alert, a message appears on the UI that is 
777 
accompanied by vibration followed by vibrations and/or sound if not acknowledged by the user 
778 
in 5 minutes. This alert remains on the screen until acknowledged by the user. The user is 
779 
prompted to check the site for occlusion and test blood glucose. 
780 
If a participant’s CGM reading is >300 mg/dL for over 2 hours or ≥400 mg/dL at any point, the 
781 
Glycemic Treatment Guidelines will be followed. 
782 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 33 of 48 
Chapter 7: Point-of-Care Testing 
783 
7.1 Point-of-Care Samples 
784 
1. HbA1c: 
785 
• Performed locally at the Screening visit or a lab result that was completed within 2 weeks 
786 
prior to the Screening visit. 
787 
2. Urine Pregnancy: 
788 
• Performed locally for females of child-bearing potential at the Screening visit and prior to the 
789 
start of the Ski Admission. 
790 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 34 of 48 
Chapter 8: Adverse Events, Device Issues, and Stopping Rules 
791 
8.1 Adverse Events 
792 
8.1.1 Definitions 
793 
Adverse Event (AE): Any untoward medical occurrence in a study participant, irrespective of the 
794 
relationship between the adverse event and the device(s) under investigation (see section 8.1.2 
795 
for reportable adverse events for this protocol). 
796 
Serious Adverse Event (SAE): Any untoward medical occurrence that: 
797 
• Results in death. 
798 
• Is life-threatening; (a non-life-threatening event which, had it been more severe, might have 
799 
become life-threatening, is not necessarily considered a serious adverse event). 
800 
• Requires inpatient hospitalization or prolongation of existing hospitalization. 
801 
• Results in persistent or significant disability/incapacity or substantial disruption of the ability 
802 
to conduct normal life functions (sight threatening). 
803 
• Is a congenital anomaly or birth defect. 
804 
• Is considered a significant medical event by the investigator based on medical judgment (e.g., 
805 
may jeopardize the participant or may require medical/surgical intervention to prevent one of 
806 
the outcomes listed above). 
807 
Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on health or safety or 
808 
any life-threatening problem or death caused by, or associated with, a device, if that effect, 
809 
problem, or death was not previously identified in nature, severity, or degree of incidence in the 
810 
investigational plan or application (including a supplementary plan or application), or any other 
811 
unanticipated serious problem associated with a device that relates to the rights, safety, or 
812 
welfare of participants (21 CFR 812.3(s)). 
813 
Adverse Device Effect (ADE): Any untoward medical occurrence in a study participant which 
814 
the device may have caused or to which the device may have contributed. 
815 
Device Complaints and Malfunctions: A device complication or complaint is something that 
816 
happens to a device or related to device performance, whereas an adverse event happens to a 
817 
participant.  A device complaint may occur independently from an AE, or along with an AE.  
818 
An AE may occur without a device complaint or there may be an AE related to a device 
819 
complaint.  A device malfunction is any failure of a device to meet its performance specifications 
820 
or otherwise perform as intended.  Performance specifications include all claims made in the 
821 
labeling for the device.  The intended performance of a device refers to the intended use for 
822 
which the device is labeled or marketed. (21 CFR 803.3).  Note: for reporting purposes, sites 
823 
will not be asked to distinguish between device complaints and malfunctions. 
824 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 35 of 48 
8.1.2 Reportable Adverse Events 
825 
For this protocol, a reportable adverse event includes any untoward medical occurrence that 
826 
meets one of the following criteria: 
827 
1. A serious adverse event 
828 
2. An Adverse Device Effect as defined in section 8.1.1, unless excluded from reporting in 
829 
section 8. 
830 
3. An Adverse Event occurring in association with a study procedure 
831 
4. Hypoglycemia meeting the definition of severe hypoglycemia as defined below  
832 
5. Diabetic ketoacidosis (DKA) as defined below or in the absence of DKA, a hyperglycemic or 
833 
ketosis event meeting the criteria defined below 
834 
Hypoglycemia and hyperglycemia not meeting the criteria below will not be recorded as adverse 
835 
events unless associated with an Adverse Device Effect.  Skin reactions from sensor placement 
836 
are only reportable if severe and/or required treatment. 
837 
Pregnancy occurring during the study will not be considered an adverse event. 
838 
8.1.2.1 Hypoglycemic Events 
839 
Hypoglycemia not associated with an Adverse Device Effect is only reportable as an adverse 
840 
event when the following definition for severe hypoglycemia is met: the event required 
841 
assistance of another person due to altered consciousness, and required another person to actively 
842 
administer carbohydrate, glucagon, or other resuscitative actions.  This means that the participant 
843 
was impaired cognitively to the point that he/she was unable to treat himself/herself, was unable 
844 
to verbalize his/ her needs, was incoherent, disoriented, and/or combative, or experienced seizure 
845 
or coma.  These episodes may be associated with sufficient neuroglycopenia to induce seizure or 
846 
coma.  If plasma glucose measurements are not available during such an event, neurological 
847 
recovery attributable to the restoration of plasma glucose to normal is considered sufficient 
848 
evidence that the event was induced by a low plasma glucose concentration. 
849 
8.1.2.2 Hyperglycemic Events/Diabetic Ketoacidosis 
850 
Hyperglycemia not associated with an Adverse Device Effect is only reportable as an adverse 
851 
event when one of the following four criteria is met:  
852 
• the event involved DKA, as defined by the Diabetes Control and Complications Trial 
853 
(DCCT) and described below 
854 
• evaluation or treatment was obtained at a health care provider facility for an acute event 
855 
involving hyperglycemia or ketosis 
856 
• blood ketone level ≥1.5 mmol/L and communication occurred with a health care provider at 
857 
the time of the event 
858 
• blood ketone level ≥3.0 mmol/L, even if there was no communication with a health care 
859 
provider 
860 
Hyperglycemic events are classified as DKA if the following are present: 
861 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 36 of 48 
• Symptoms such as polyuria, polydipsia, nausea, or vomiting; 
862 
• Serum ketones ≥1.5 mmol/L or large/moderate urine ketones; 
863 
• Either arterial blood pH <7.30 or venous pH <7.24 or serum bicarbonate <15; and 
864 
• Treatment provided in a health care facility 
865 
All reportable Adverse Events—whether volunteered by the participant, discovered by study 
866 
personnel during questioning, or detected through physical examination, laboratory test, or other 
867 
means—will be reported on an adverse event form online.  Each adverse event form is reviewed 
868 
by the Medical Monitor to verify the coding and the reporting that is required. 
869 
8.1.3 Relationship of Adverse Event to Study Device 
870 
The study investigator will assess the relationship of any adverse event to be related, possibly 
871 
related, or unrelated by determining if there is a reasonable possibility that the adverse event may 
872 
have been caused by the study device. 
873 
8.1.4 Intensity of Adverse Event 
874 
The intensity of an adverse event will be rated on a three point scale: (1) mild, (2) moderate, or 
875 
(3) severe.  It is emphasized that the term severe is a measure of intensity: thus a severe adverse 
876 
event is not necessarily serious.  For example, itching for several days may be rated as severe, 
877 
but may not be clinically serious. 
878 
• MILD: Usually transient, requires no special treatment, and does not interfere with the 
879 
participant’s daily activities. 
880 
• MODERATE: Usually causes a low level of inconvenience or concern to the participant and 
881 
may interfere with daily activities, but is usually ameliorated by simple therapeutic measures. 
882 
• SEVERE: Interrupts a participant’s usual daily activities and generally requires systemic 
883 
drug therapy or other treatment. 
884 
8.1.5 Coding of Adverse Events 
885 
Adverse events will be coded using the MedDRA dictionary.  The Medical Monitor will review 
886 
the investigator’s assessment of causality and may agree or disagree.  Both the investigator’s and 
887 
Medical Monitor’s assessments will be recorded.  The Medical Monitor will have the final say in 
888 
determining the causality. 
889 
Adverse events that continue after the participant’s discontinuation or completion of the study 
890 
will be followed until their medical outcome is determined or until no further change in the 
891 
condition is expected. 
892 
8.1.6 Outcome of Adverse Event 
893 
The outcome of each reportable adverse event will be classified by the investigator as follows: 
894 
• RECOVERED/RESOLVED – The participant recovered from the AE/SAE without sequelae.  
895 
Record the AE/SAE stop date. 
896 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 37 of 48 
• RECOVERED/RESOLVED WITH SEQUELAE – The event persisted and had stabilized 
897 
without change in the event anticipated.  Record the AE/SAE stop date. 
898 
• FATAL – A fatal outcome is defined as the SAE that resulted in death.  Only the event that 
899 
was the cause of death should be reported as fatal.  AEs/SAEs that were ongoing at the time 
900 
of death; however, were not the cause of death, will be recorded as “resolved” at the time of 
901 
death. 
902 
• NOT RECOVERED/NOT RESOLVED (ONGOING) – An ongoing AE/SAE is defined as 
903 
the event was ongoing with an undetermined outcome. 
904 
 An ongoing outcome will require follow-up by the site in order to determine the final 
905 
outcome of the AE/SAE. 
906 
 The outcome of an ongoing event at the time of death that was not the cause of death, 
907 
will be updated and recorded as “resolved” with the date of death recorded as the stop 
908 
date. 
909 
• UNKNOWN – An unknown outcome is defined as an inability to access the participant or 
910 
the participant’s records to determine the outcome (for example, a participant that was lost to 
911 
follow-up). 
912 
All clinically significant abnormalities of clinical laboratory measurements or adverse events 
913 
occurring during the study and continuing at study termination should be followed by the 
914 
participant’s physician and evaluated with additional tests (if necessary) until diagnosis of the 
915 
underlying cause, or resolution.  Follow-up information should be recorded on source 
916 
documents. 
917 
If any reported adverse events are present when a participant completes the study, or if a 
918 
participant is withdrawn from the study due to an adverse event, the participant will be contacted 
919 
for re-evaluation within 2 weeks.  If the adverse event has not resolved, additional follow-up will 
920 
be performed as appropriate.  Every effort should be made by the Investigator or delegate to 
921 
contact the participant until the adverse event has resolved or stabilized. 
922 
8.2 Reportable Device Issues 
923 
All UADEs, ADEs, device complaints, and device malfunctions will be reported irrespective of 
924 
whether an adverse event occurred, except in the following circumstances. 
925 
The following device issues are anticipated and will not be reported but will be reported as an 
926 
Adverse Event if the criteria for AE reporting described above are met: 
927 
• Component disconnections 
928 
• CGM sensors lasting fewer than the number of days expected per CGM labeling 
929 
• CGM tape adherence issues 
930 
• Pump infusion set occlusion not leading to ketosis 
931 
• Battery lifespan deficiency due to inadequate charging or extensive wireless communication 
932 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 38 of 48 
• Intermittent device component disconnections/communication failures not leading to system 
933 
replacement 
934 
• Device issues clearly addressed in the user guide manual that do not require additional 
935 
troubleshooting 
936 
• Skin reactions from CGM sensor placement or pump infusion set placement that do not meet 
937 
criteria for AE reporting 
938 
8.3 Pregnancy Reporting 
939 
If pregnancy occurs, the participant will be discontinued from the study.  The occurrence of 
940 
pregnancy will be reported on an AE Form. 
941 
8.4 Timing of Event Reporting 
942 
SAEs must be reported to the IRB per IRB reporting guidelines for this protocol. 
943 
Other reportable adverse events, device malfunctions (with or without an adverse event), and 
944 
device complaints should be reported promptly by completion of an electronic case report form, 
945 
but there is no formal required reporting period. 
946 
Upon knowledge of an UADE, the investigator will investigate the UADE and if indicated, 
947 
report the results of the investigation to the IRB, and the FDA within ten working days of the 
948 
investigator becoming aware of the UADE per 21CFR 812.46(b) (2). The Medical Monitor must 
949 
determine if the UADE presents an unreasonable risk to participants. If so, the Medical Monitor 
950 
must ensure that all investigations, or parts of investigations presenting that risk, are terminated 
951 
as soon as possible but no later than 5 working days after the Medical Monitor makes this 
952 
determination and no later than 15 working days after first receipt notice of the UADE. 
953 
In the case of a device system component malfunction (e.g. pump, CGM, control algorithm), 
954 
information will be forwarded to the responsible company by the site personnel, to be handled 
955 
by its complaint management system. 
956 
8.5 Stopping Criteria 
957 
8.5.1 Participant Discontinuation of Study Device 
958 
Rules for discontinuing study device use are described below. 
959 
• The investigator believes it is unsafe for the participant to continue on the intervention.  This 
960 
could be due to the development of a new medical condition or worsening of an existing 
961 
condition; or participant behavior contrary to the indications for use of the device that 
962 
imposes on the participant’s safety 
963 
• The participant requests that the treatment be stopped 
964 
• Participant pregnancy 
965 
• One episode of DKA 
966 
• One severe hypoglycemia event as defined in section 8.1.2.1 
967 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 39 of 48 
If pregnancy occurs, the participant will be discontinued from the study entirely. Otherwise, even 
968 
if the study device system is discontinued, the participant will be encouraged to remain in the 
969 
study through the final study visit. 
970 
8.5.2 Criteria for Suspending or Stopping Overall Study 
971 
In the case of a system malfunction resulting in a severe hypoglycemia or severe hyperglycemia 
972 
event (as defined in section 8.1.2.2), use of the study device system will be suspended while the 
973 
problem is diagnosed. 
974 
In addition, study activities could be similarly suspended if the manufacturer of any constituent 
975 
study device requires stoppage of device use for safety reasons (e.g. product recall).  The 
976 
affected study activities may resume if the underlying problem can be corrected by a protocol or 
977 
system modification that will not invalidate the results obtained prior to suspension. 
978 
The study medical monitor will be informed of all serious adverse events and any unanticipated 
979 
adverse device events that occur during the study and will review compiled safety data at 
980 
periodic intervals.  The medical monitor may request suspension of study activities or stoppage 
981 
of the study if deemed necessary based on the totality of safety data available. 
982 
8.6 Risks 
983 
The potential risks associated with use of the study device are described in section 1.3. 
984 
Additional risks are minor and/or infrequent and include: 
985 
• Pain, bruising, redness, or infection from blood draws 
986 
• Loss of confidentiality 
987 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 40 of 48 
Chapter 9: Miscellaneous Considerations 
988 
9.1 Drugs Used as Part of the Protocol 
989 
Participants will use either lispro or aspart insulin prescribed by their personal physician. 
990 
9.2 Prohibited Medications, Treatments, and Procedures 
991 
Participants using glulisine at the time of enrollment will be asked to contact their personal 
992 
physician to change their prescribed personal insulin to lispro or aspart for the duration of the 
993 
trial. 
994 
Treatment with any non-insulin glucose-lowering agent (including GLP-1 agonists, Symlin, 
995 
DPP-4 inhibitors, SGLT-2 inhibitors, biguanides, sulfonylureas and naturaceuticals) will be 
996 
reviewed by the study team.  Use of these agents must be approved by the investigator prior to 
997 
initiation of study equipment. 
998 
The investigational study devices (t:slim X2 insulin pump, study CGM systems) must be 
999 
removed before Magnetic Resonance Imaging (MRI), Computed Tomography (CT) or diathermy 
1000 
treatment. Participants may continue in the trial after temporarily discontinuing use if requiring 
1001 
one of the treatments above. 
1002 
9.3 Participant Compensation 
1003 
Participants will not receive compensation or reimbursement for his/her participation in this 
1004 
study. 
1005 
9.4 Participant Withdrawal 
1006 
Participation in the study is voluntary, and a participant may withdraw at any time.  
1007 
For participants who withdraw, their data will be used up until the time of withdrawal. 
1008 
9.5 Confidentiality 
1009 
For security and confidentiality purposes, participants will be assigned an identifier that will 
1010 
be used instead of their name.  De-identified participant information may also be provided to 
1011 
Tandem for system evaluation purposes. 
1012 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 41 of 48 
Chapter 10: Statistical Consideration 
1013 
10.1 Statistical and Analytical Plans 
1014 
The approach to sample size and statistical analyses are summarized below.  A detailed statistical 
1015 
analysis plan will be written and finalized prior to the first tabulation of data by treatment group 
1016 
(ie, for DSMB review).  The analysis plan synopsis in this chapter contains the framework of the 
1017 
anticipated final analysis plan. 
1018 
10.2 Statistical Hypotheses 
1019 
The hypotheses for the primary outcome are: 
1020 
a. Null Hypothesis: the use of MyTDI results in a decreased percentage of the time spent 
1021 
between 70-180mg/dL during home use 
1022 
b. Alternative Hypothesis : the use of MyTDI does not results in a decreased percentage of 
1023 
the time spent between 70-180mg/dL during home use 
1024 
All outcomes will be analyzed using repeated measure ANOVA between baseline and the 
1025 
studied period, using within-between factors. 
1026 
We will compute all outcome for baseline, camp, and the final home segment. Outcomes will be 
1027 
further refined to focus on daytime (7am-11pm), nighttime (11pm-7am), and for the Ski 
1028 
Admission, ski time (9am-noon & 1:30pm-4:30) 
1029 
10.3 Sample Size 
1030 
We set the study to detect an effect size of 0.25 using repeated measure ANOVA and a within-
1031 
between comparison (baseline – home, grouped by treatment), assuming 0.75 correlation 
1032 
between measurements. With N=20 we expect to reach 85% power, allowing for up to 2 
1033 
participants (10%) to fail to complete the study. 
1034 
10.4 Outcome Measures 
1035 
10.4.1 Primary Efficacy Endpoint 
1036 
The primary outcome for this study is the percent of time spent between 70mg/dL and 180mg/dL 
1037 
as computed by the number of CGM values falling in this interval divided by the total number of 
1038 
available CGM values. CGM gaps inferior to 3 hours will be linearly interpolated 
1039 
10.4.2 Secondary Efficacy Endpoints 
1040 
Additional CGM outcomes will include: 
1041 
• Percent CGM below 50mg/dL 
1042 
• Percent CGM below 54mg/dL 
1043 
• Percent below 60mg/dL 
1044 
• Percent CGM below 70mg/dL 
1045 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 42 of 48 
• Percent CGM above 180mg/dL 
1046 
• Percent CGM above 250mg/dL 
1047 
• Percent CGM above 300mg/dL: 
1048 
• Average CGM 
1049 
• CGM coefficient of variation 
1050 
• CGM based LBGI & HBGI 
1051 
Furthermore, we will compute 
1052 
• Total amount of insulin used 
1053 
• Number of Hypoglycemic episodes as defined by contiguous CGM below 70mg/dL 
1054 
• Number of rescue CHO 
1055 
• Total amount of rescues CHO 
1056 
10.4.2.1 Safety Analyses 
1057 
All randomized participants will be included in these analyses and the circumstances of all 
1058 
reportable cases of the following will be summarized and tabulated by treatment group: 
1059 
• Severe hypoglycemia 
1060 
• Diabetic ketoacidosis 
1061 
• Other serious adverse events and serious adverse device events 
1062 
• Unanticipated adverse device effects 
1063 
10.5 Device Issues 
1064 
The following tabulations and analyses will be performed by treatment group to assess device 
1065 
issues: 
1066 
• Device malfunctions requiring study team contact and other reported device issues 
1067 
• Sensor performance metrics (difference, absolute relative difference, and International 
1068 
Organization for Standardization criteria) – if applicable, by sensor version. 
1069 
• % time CGM data available -  overall and by month 
1070 
The following tabulations will be performed for the CLC arm only: 
1071 
• Performance metrics, describing the Control-IQ system and its components like: 
1072 
 % time CGM data were available to the Control-IQ system – overall and by month 
1073 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 43 of 48 
 % time in different operational modes per week - overall and by month  
1074 
 Rate of different failure events and alarms per 24 hours recorded by the Control-IQ 
1075 
system – overall and by month 
1076 
 
1077 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 44 of 48 
Chapter 11: Data Collection and Monitoring 
1078 
11.1 Case Report Forms and Device Data 
1079 
The main study data are collected through a combination of case report forms (CRFs) and 
1080 
electronic device data files obtained from the study software and individual hardware 
1081 
components.  These electronic device files and electronic CRFs from the study website are 
1082 
considered the primary source documentation. 
1083 
When data are directly collected in electronic case report forms, this will be considered the 
1084 
source data.  Each participating site will maintain appropriate medical and research records for 
1085 
this trial, in compliance with ICH E6 and regulatory and institutional requirements for the 
1086 
protection of confidentiality of participants. 
1087 
11.2 Study Records Retention 
1088 
Study documents should be retained for a minimum of 2 years after the last approval of a 
1089 
marketing application in an ICH region and until there are no pending or contemplated marketing 
1090 
applications in an ICH region or until at least 2 years have elapsed since the formal 
1091 
discontinuation of clinical development of the investigational product.  These documents should 
1092 
be retained for a longer period, however, if required by local regulations.  No records will be 
1093 
destroyed without the written consent of the sponsor, if applicable.  It is the responsibility of the 
1094 
sponsor to inform the investigator when these documents no longer need to be retained. 
1095 
11.3 Protocol Deviations 
1096 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or procedure 
1097 
requirements.  The noncompliance may be either on the part of the participant, the investigator, 
1098 
or the study site staff.  As a result of deviations, corrective actions are to be developed by the site 
1099 
and implemented promptly.  The site PI/study staff is responsible for knowing and adhering to 
1100 
their IRB requirements.   
1101 

UNIVERSITY OF VIRGINIA 
180030 – Winter Study 2019 v1.4 
Page 45 of 48 
Chapter 12: Ethics/Protection of Human Participants 
1102 
12.1 Ethical Standard 
1103 
The investigator will ensure that this study is conducted in full conformity with Regulations for 
1104 
the Protection of Human Participants of Research codified in 45 CFR Part 46, 21 CFR Part 50, 
1105 
21 CFR Part 56, and/or the ICH E6. 
1106 
12.2 Institutional Review Boards 
1107 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
1108 
be submitted to the IRB for review and approval.  Approval of both the protocol and the consent 
1109 
form must be obtained before any participant is enrolled.  Any amendment to the protocol will 
1110 
require review and approval by the IRB before the changes are implemented to the study.  All 
1111 
changes to the consent form will be IRB approved; a determination will be made regarding 
1112 
whether previously consented participants need to be re-consented. 
1113 
12.3 Informed Consent Process 
1114 
12.3.1 Consent Procedures and Documentation 
1115 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
1116 
the study and continues throughout the individual’s study participation.  Extensive discussion of 
1117 
risks and possible benefits of participation will be provided to the participants and their families.  
1118 
Consent forms will be IRB-approved.  The participant will be asked to read and review the 
1119 
document.  The investigator will explain the research study to the participant and answer any 
1120 
questions that may arise.  All participants will receive a verbal explanation in terms suited to 
1121 
their comprehension of the purposes, procedures, and potential risks of the study and of their 
1122 
rights as research participants.  Participants will have the opportunity to carefully review the 
1123 
written consent form and ask questions prior to signing. 
1124 
The participants should have the opportunity to discuss the study with their surrogates or think 
1125 
about it prior to agreeing to participate.  The participant will sign the informed consent document 
1126 
prior to any procedures being done specifically for the study.  The participants may withdraw 
1127 
consent at any time throughout the course of the trial.  A copy of the informed consent document 
1128 
will be given to the participants for their records.  The rights and welfare of the participants will 
1129 
be protected by emphasizing to them that the quality of their medical care will not be adversely 
1130 
affected if they decline to participate in this study. 
1131 
12.3.2 Participant and Data Confidentiality 
1132 
The medical monitor, other authorized representatives of the sponsor, representatives of the IRB 
1133 
or device company supplying study product may inspect all documents and records required to 
1134 
be maintained by the investigator, including but not limited to, medical records (office, clinic, or 
1135 
hospital) for the participants in this study.  The clinical study site will permit access to such 
1136 
records. 
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The study participant’s contact information will be securely stored for internal use during the 
1138 
study.  At the end of the study, all records will continue to be kept in a secure location for as long 
1139 
a period as dictated by local IRB and Institutional regulations. 
1140 

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Chapter 13: References 
1141 
1.  
Anderson SM, Raghinaru D, Pinsker JE, et al. Multinational Home Use of Closed-Loop 
1142 
Control Is Safe and Effective. Diabetes Care 2016;39:1143-50. 
1143 
2.  
Breton MD, Brown SA, Karvetski CH, et al. Adding heart rate signal to a control-to-
1144 
range artificial pancreas system improves the protection against hypoglycemia during exercise in 
1145 
type 1 diabetes. Diabetes Technol Ther 2014;16:506-11. 
1146 
3.  
Breton MD, Chernavvsky DR, Forlenza GP, et al. Closed-Loop Control During Intense 
1147 
Prolonged Outdoor Exercise in Adolescents With Type 1 Diabetes: The Artificial Pancreas Ski 
1148 
Study. Diabetes Care 2017;40:1644-50. 
1149 
4.  
Breton MD, Patek SD, Lv D, et al. Continuous Glucose Monitoring and Insulin Informed 
1150 
Advisory System with Automated Titration and Dosing of Insulin Reduces Glucose Variability 
1151 
in Type 1 Diabetes Mellitus. Diabetes Technol Ther 2018;20:531-40. 
1152 
5.  
Chernavvsky DR, DeBoer MD, Keith-Hynes P, et al. Use of an artificial pancreas among 
1153 
adolescents for a missed snack bolus and an underestimated meal bolus. Pediatr Diabetes 
1154 
2016;17:28-35. 
1155 
6.  
Cobelli C, Renard E, Kovatchev BP, et al. Pilot Studies of Wearable Outpatient Artificial 
1156 
Pancreas in Type 1 Diabetes. Diabetes Care 2012;35:e65-e7. 
1157 
7.  
DeBoer MD, Breton MD, Wakeman C, et al. Performance of an Artificial Pancreas 
1158 
System for Young Children with Type 1 Diabetes. Diabetes Technol Ther 2017;19:293-8. 
1159 
8.  
DeBoer MD, Chernavvsky DR, Topchyan K, Kovatchev BP, Francis GL, Breton MD. 
1160 
Heart rate informed artificial pancreas system enhances glycemic control during exercise in 
1161 
adolescents with T1D. Pediatr Diabetes 2017;18:540-6. 
1162 
9.  
Del Favero S, Boscari F, Messori M, et al. Randomized Summer Camp Crossover Trial 
1163 
in 5- to 9-Year-Old Children: Outpatient Wearable Artificial Pancreas Is Feasible and Safe. 
1164 
Diabetes Care 2016;39:1180-5. 
1165 
10.  
Gildersleeve R, Riggs SL, Chernavvsky DR, Breton MD, DeBoer MD. Improving the 
1166 
Safety and Functionality of an Artificial Pancreas System for Use in Younger Children: Input 
1167 
from Parents and Physicians. Diabetes Technol Ther 2017;19:660-74. 
1168 
11.  
Keith-Hynes P, Guerlain S, Mize B, et al. DiAs user interface: a patient-centric interface 
1169 
for mobile artificial pancreas systems. J Diabetes Sci Technol 2013;7:1416-26. 
1170 
12.  
Keith-Hynes P, Mize B, Robert A, Place J. The Diabetes Assistant: A Smartphone-Based 
1171 
System for Real-Time Control of Blood Glucose. Electronics 2014;3:609. 
1172 
13.  
Kovatchev BP, Renard E, Cobelli C, et al. Feasibility of outpatient fully integrated 
1173 
closed-loop control: first studies of wearable artificial pancreas. Diabetes Care 2013;36:1851-8. 
1174 
14.  
Kovatchev BP, Renard E, Cobelli C, et al. Safety of outpatient closed-loop control: first 
1175 
randomized crossover trials of a wearable artificial pancreas. Diabetes Care 2014;37:1789-96. 
1176 
15.  
Kovatchev B, Cheng P, Anderson SM, et al. Feasibility of Long-Term Closed-Loop 
1177 
Control: A Multicenter 6-Month Trial of 24/7 Automated Insulin Delivery. Diabetes Technol 
1178 
Ther 2017;19:18-24. 
1179 

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16.  
Ly TT, Buckingham BA, DeSalvo DJ, et al. Day-and-Night Closed-Loop Control Using 
1180 
the Unified Safety System in Adolescents With Type 1 Diabetes at Camp. Diabetes Care. United 
1181 
States2016:e106-7. 
1182 
17.  
Place J, Robert A, Ben Brahim N, et al. DiAs web monitoring: a real-time remote 
1183 
monitoring system designed for artificial pancreas outpatient trials. J Diabetes Sci Technol 
1184 
2013;7:1427-35. 
1185 
18.  
Sanchez-Pena R, Colmegna P, Garelli F, et al. Artificial Pancreas: Clinical Study in Latin 
1186 
America Without Premeal Insulin Boluses. J Diabetes Sci Technol 2018;12:914-25. 
1187 
19.  
Thabit H, Hovorka R. Coming of age: the artificial pancreas for type 1 diabetes. 
1188 
Diabetologia 2016;59:1795-805. 
1189 
20.  
Troncone A, Bonfanti R, Iafusco D, et al. Evaluating the Experience of Children With 
1190 
Type 1 Diabetes and Their Parents Taking Part in an Artificial Pancreas Clinical Trial Over 
1191 
Multiple Days in a Diabetes Camp Setting. Diabetes Care 2016;39:2158-64. 
1192 
21.  
Zisser H, Renard E, Kovatchev B, et al. Multicenter closed-loop insulin delivery study 
1193 
points to challenges for keeping blood glucose in a safe range by a control algorithm in adults 
1194 
and adolescents with type 1 diabetes from various sites. Diabetes Technol Ther 2014;16:613-22 
1195 
 
1196