A Randomized, Two-way, Cross-over Study to Assess the Efficacy of an MPC Exercise-enabled Closed-loop System vs FMPD Exercise-enabled Closed-loop System
Phase: NA
Conditions: Type 1 Diabetes
Sponsor: Oregon Health and Science University

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PROTOCOL TITLE: A randomized, two-way, cross-over study to assess the efficacy of an 
MPC exercise-enabled closed-loop system vs FMPD exercise-enabled closed-loop system  
 
  
STUDY SITE: 
Oregon Health Science University 
3181 SW Sam Jackson Park Rd 
Portland, OR 97239 
 
FUNDING: 
JDRF & Helmsley Charitable Trust  
 
PRINCIPAL INVESTIGATORS: 
Jessica R. Castle MD; Peter Jacobs PhD  
 
CO-INVESTIGATORS:  
Joseph El Youssef MBBS 
Leah Wilson MD 
Melanie Jackson MD 
 
Background: 
 
Closed-loop systems automate insulin delivery based on continuous glucose monitoring (CGM) 
values to minimize hypoglycemia and hyperglycemia, and in some cases also deliver glucagon to 
prevent and treat hypoglycemia. Closed-loop systems have been tested extensively in both the 
inpatient and outpatient settings. Our group has previously developed both an insulin-only 
closed-loop system and a dual-hormone (insulin and glucagon) closed-loop system. The novelty 
of these closed-loop systems are their ability to automatically detect exercise and adjust dosing in 
response to the exercise. Recently, we completed an outpatient closed-loop study, which tested 
the OHSU insulin-only closed-loop system with automated exercise detection [1]. Participants 
participated in four arms in randomized order: current care (their typical diabetes care, which 
included an insulin pump with or without a sensor), sensor-augmented pump with predictive low 
glucose suspend (using a t:slim pump and Dexcom G5 sensor with a PLGS algorithm running on 
the smartphone), insulin-only closed-loop system with exercise detection, and bi-hormonal 
(insulin + glucagon) closed-loop system with exercise detection. Each arm was 4 days long, with 
two 12 hour in clinic visits on days 1 and 4, with the remainder of the time spent as an outpatient 
using a cloud-based remote monitoring system. During the time spent as an outpatient, 
participants went to work, slept at home, travelled, and even went skiing. Participants performed 
moderate exercise for 45 minutes at 60% VO2max during both of the in clinic visits as well as 
performed one at home exercise session. The primary endpoints were percent time in 
hypoglycemia (CGM <70 mg/dL) and percent time in target (CGM 70-180 mg/dL) expressed as 
mean (SD). The mean time in hypoglycemia was the lowest with dual-hormone during the 
exercise period: 3.4±4.5% vs. 8.3±12.6% single-hormone (p=0.009) vs 7.6±8.0% predictive low 
glucose suspend (p<0.001) vs 4.3±6.8% current care where pre-exercise insulin adjustments 
were allowed (p=0.49). This type of manual adjustment was not allowed in any other arm and no 
snacks were given prior to exercise. Time in hypoglycemia was also the lowest with dual-
hormone during the entire 4-day study: 1.3±1.0% vs. 2.8±1.7% single-hormone (p<0.001) vs. 
2.0±1.5% predictive low glucose suspend (p=0.04) vs. 3.1±3.2% current care (p=0.007). Time in 
range during the entire study was the highest with insulin-only closed-loop system: 74.3±8.0% 
vs 72.0±10.8% dual-hormone (p=0.44). The OHSU insulin-only closed-loop system performance 

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was comparable to those reported in a recent meta-analysis of AP studies [2] which reported a 
mean time in range of 70.8% using insulin-only closed-loop systems vs 74.3% in our recent 
study. We have also completed a study on patients with T1D who used the OHSU dual-hormone 
AP for 22 hours within the hospital during which participants performed mild exercise for 45 
minutes on a treadmill [3]. For this study, we used the OHSU bi-hormonal artificial pancreas 
system that adjusts dosing after an exercise announcement to reduce exercise-related 
hypoglycemia. Results showed that adjusting hormones during exercise reduced hypoglycemia. 
 
The study described within this protocol is designed to test the efficacy of a new modified 
insulin-only closed-loop algorithm, a model-predictive control (MPC) algorithm that modulates 
insulin delivery based on estimated activity level. The potential benefit of this type of algorithm 
is that it handles exercise not as a discrete event, but it automatically adjusts insulin delivery 
based on estimated activity level. This type of algorithm may significantly improve glucose 
control over the FMPD algorithm which is designed only to detect exercise over 4 metabolic 
equivalent of tasks (METs) for a specific duration of 45 minutes.      
  
Primary Objective: 
• To confirm superiority of the OHSU MPC exercise-enabled closed-loop system as 
measured by percent of time with sensed glucose less than 70 mg/dl as compared to the 
OHSU FMPD exercise-enabled closed-loop system.    
 
Secondary Objective: 
• To confirm superiority of the OHSU MPC exercise-enabled closed-loop as measured by 
other glucose metrics as compared to the OHSU FMPD exercise-enabled closed loop 
system.    
Study Hypothesis: 
We propose that the use of the OHSU MPC exercise-enabled closed-loop system as compared to 
the OHSU FMPD exercise-enabled closed-loop system will increase the time in range as 
measured by sensed glucose values.   
 
Endpoints 
Primary Endpoint:  
• Percent of time with sensed glucose <70 mg/dl across the duration of inpatient day (Day 
3 MPC vs. Day 1 FMPD) 
Secondary Endpoints:  
• Percent of time with sensed glucose between 70-180 mg/dl across the study duration 
• Percent of time with sensed glucose between 70-180 mg/dl across the duration of the 
inpatient day (Day 3 MPC vs. Day 1 FMPD) 

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• Percent of time with sensed glucose between 70 – 180 mg/dl from the start of the in-
clinic exercise session until the start of the next meal  
• Percent of time with sensed glucose <70 mg/dl from the start of the in-clinic exercise 
session until the start of the next meal 
• Number of carbohydrate treatments (defined as 15 or 20 grams of carbohydrate)   
• Mean sensed glucose 
• Coefficient of variation of glucose  
• Percent of time with sensed glucose <54 mg/dl 
• Percent of time with sensed glucose >180 mg/dl 
• Mean amount of insulin delivered per day (in units/kg) 
Study Type  
This is a single center, randomized, two treatment, crossover trial designed to compare the 
glucose control resulting from the use of the OHSU MPC exercise-enabled AP system as 
compared to the OHSU FMPD exercise-enabled AP system.  
 
Study Population 
Study population will be adults with type 1 diabetes, ages 21 – 50 years of age.  Older 
participants are excluded due to higher risk of unrecognized coronary artery disease.  Younger 
participants are excluded as it is appropriate to assess safety first in the adult population. Twenty-
five participants will be recruited to participate in studies.   
 
Power Analysis 
A sample of 24 subjects provides at least 80% power to detect a paired difference for a two-sided 
Wilcoxon signed-rank test of the difference between use of exercise-enabled MPC algorithm and 
FMPD algorithm with alpha set at 0.05 for our primary outcome of percent of time <70 mg/dl. 
We use the sample size for a one-sample t-test, n, with an adjustment factor for the double 
exponential (or Laplace) distribution of the difference such that the final sample size n' = n/(2/3). 
We anticipate a mean difference of 1.2 (SD 2.5) based on our prior published AP study data. For 
normally-distributed secondary outcomes, we have >80% power to detect differences of 0.6 SD 
or greater using a two-sided one-sample t-test for the mean difference at the 0.05 significance 
level. These calculations were performed using PASS version. We propose to enroll 25 
participants in this study as this will yield more than 80% power as stated above (see Participant 
Recruiting).   
 
Protocol Summary: 
Participants will undergo two approximately 76 hour studies.  See Figure 1 &2 for a diagram of 
the study flow and structure. During each of these intervention visits, participants will wear an 
Omnipod to deliver insulin and a Dexcom G6 CGM to measure glucose.  The CGM system will 
provide sensed glucose data every 5 minutes.  Sensed glucose data will be wirelessly transmitted 
via Bluetooth Low Energy (BTLE) from the Dexcom G6 transmitter to the smartphone master 
controller every five minutes.  The smart phone will wirelessly communicate via BTLE to an 
Omnipod through a PDM (Insulet Corp.). During one of the studies, glucose will be controlled 

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using the MPC exercise-enabled mode.  During another study, glucose will be controlled using 
the FMPD exercise-enabled mode.  The closed loop system will receive activity data through a 
Polar M600 watch worn by the participant. Participants will arrive at the clinic at approximately 
7am for the inpatient visits.  Participants will eat breakfast, lunch and dinner at approximately 
8am, noon, and 5pm respectively.  Participants will perform activities of daily living and 
exercise. Participants will be discharged at approximately 7pm. Participants will then go home 
for the remainder of the study visit and perform two exercise sessions at home.  Participants will 
return to OHSU on Day 4 for removal of all devices.  The exception to this is for the first 8 
participants using the MPC exercise-enable mode. These participants will stay at OHSU during 
the day and go home to sleep each night (7pm-7am). These participants will use the system in 
open-loop mode while off campus. 
Figure 1: Study Flow Design 
 
 
Figure 2: Study structure 

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Participant Criteria 
Inclusion Criteria:  
1. Diagnosis of type 1 diabetes mellitus for at least 1 year.  
2. Male or female participants 21 to 50 years of age.  
3. Physically willing and able to perform aerobic exercise (as determined by the investigator 
after reviewing the participant’s activity level)  
4. Current use of an insulin pump for at least 3 months with stable insulin pump settings for 
>2 weeks.   
5. Lives with another person age 18 or older who will be present while participant exercises 
at home and that can attend the training on using the system. 
6. Lives within 40 miles of OHSU main campus. 
7. HbA1c ≤ 10% at screening.    
8. Total daily insulin requirement is less than 139 units/day.  
9. Current use of a phone or other device so can be contacted by study staff off-campus 
10. Willingness to follow all study procedures, including attending all clinic visits.  
11. Willingness to sign informed consent and HIPAA documents.  
 
Exclusion Criteria:  
1. Female of childbearing potential who is pregnant or intending to become pregnant or 
breast-feeding, or is not using adequate contraceptive methods. Acceptable contraception 
includes birth control pill / patch / vaginal ring, Depo-Provera, Norplant, an IUD, the 
double barrier method (the woman uses a diaphragm and spermicide and the man uses a 
condom), or abstinence. 
2. Any cardiovascular disease, defined as a clinically significant EKG abnormality at the 
time of screening or any history of: stroke, heart failure, myocardial infarction, angina 
Day 1
Day 2
Day 3
Day 4
Inpatient
Inpatient
Inpatient
Study ends
Day 1
Inpatient
MPC  
(first n=8)
FMPD
(n = 24)
Day 1
Day 2
Day 3
Day 4
Inpatient
At home
At home
MPC
(last n=16)
At home
At home
At home
At home
At home
At home
Day 2
Day 3
Day 4
At home
At home
At home
At home
At home
Study ends
Study ends
Overnight
Overnight
Overnight

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pectoris, or coronary arterial bypass graft or angioplasty. Diagnosis of 2nd or 3rd degree 
heart block or any non-physiological arrhythmia judged by the investigator to be 
exclusionary. 
3. Renal insufficiency (GFR < 60 ml/min, using the MDRD equation as reported by the 
OHSU laboratory). 
4. Liver failure, cirrhosis, or any other liver disease that compromises liver function as 
determined by the investigator.   
5. Hematocrit of less than 36% for men, less than 32% for women. 
6. Hypertensive participants with systolic blood pressure ≥ 160 mmHg or diastolic blood 
pressure ≥ 100 mmHg despite treatment or who have treatment-refractory hypertension 
(e.g. requiring four or more medications).  
7. History of severe hypoglycemia during the past 12 months prior to screening visit or 
hypoglycemia unawareness as judged by the investigator. Participants will complete a 
hypoglycemia awareness questionnaire.  Participants will be excluded for four or more R 
responses.  
8. History of diabetes ketoacidosis during the prior 6 months prior to screening visit, as 
diagnosed on hospital admission or as judged by the investigator. 
9. Adrenal insufficiency. 
10. Any active infection. 
11. Known or suspected abuse of alcohol, narcotics, or illicit drugs.  
12. Seizure disorder. 
13. Active foot ulceration. 
14. Severe peripheral arterial disease characterized by ischemic rest pain or severe 
claudication. 
15. Major surgical operation within 30 days prior to screening. 
16. Use of an investigational drug within 30 days prior to screening. 
17. Chronic usage of any immunosuppressive medication (such as cyclosporine, 
azathioprine, sirolimus, or tacrolimus). 
18. Bleeding disorder, treatment with warfarin, or platelet count below 50,000. 
19. Allergy to aspart or lispro insulin. 
20. Current administration of oral or parenteral corticosteroids. 
21. Any life threatening disease, including malignant neoplasms and medical history of 
malignant neoplasms within the past 5 years prior to screening (except basal and 
squamous cell skin cancer).  
22. Beta blockers or non-dihydropyridine calcium channel blockers. 
23. Current use of any medication intended to lower glucose other than insulin (ex. use of 
liraglutide). 
24. A positive response to any of the questions from the Physical Activity Readiness 
Questionnaire with one exception: participant will not be excluded if he/she takes a single 

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blood pressure medication that doesn’t impact heart rate and blood pressure is controlled 
on the medication (blood pressure is less than 140/90 mmHg).  
25. Any chest discomfort with physical activity, including pain or pressure, or other types of 
discomfort.  
26. Any clinically significant disease or disorder which in the opinion of the Investigator may 
jeopardize the participant’s safety or compliance with the protocol.  
Participant Recruiting: 
Participants will be recruited from OHSU clinics, from flyers to be posted in approved places at 
OHSU or posted on the web to the clinical trials page for the OHSU Schnitzer Diabetes Clinic, to 
the Clinic’s facebook group, ads on facebook, electronic newsletter or from the OHSU 
Participant Recruitment website. The T1D Exchange may send out approved recruitment emails 
to Glu community users in the Portland/Vancouver area. Handouts may also be made available 
to faculty at Tuality, Providence, Kaiser, and Legacy to pass along to patients/participants who 
show interest in the study. Records from OHSU Schnitzer Diabetes Clinic patients may be 
screened to find potential participants. Participants will also be recruited from a list of 
participants who participated in past OHSU studies who have agreed to be contacted regarding 
future studies involving Drs. Castle from the OHSU diabetes research registry and/or 
www.clinicaltrials.gov. Non-english speaking participants will not be recruited since this 
protocol would require the use of medical devices and mobile software that do not have non-
english versions available. Up to 50 participants may be screened in this study.  Goal enrollment 
is 25 participants.  
 
Withdrawal Criteria 
The participant may withdraw at will at any time or at the discretion of the Investigator.  
A participant must be withdrawn if the following applies: 
• Hypoglycemia during the treatment period posing a safety problem as judged by the 
investigator.  
• Hyperglycemia during the treatment period posing a safety problem as judged by the 
investigator.  
• Protocol deviation having influence on efficacy or safety data as judged by the 
Investigator.  
• Substantial and repeated non-compliance with trial procedures.  
• Pregnancy.  
• Intention of becoming pregnant.  
Visit Procedures 
Screening (Visit 1) 
Screening will take place within 12 weeks prior to the 1 week run-in period (Visit 2).  All 
screening visits will take place at OHSU’s Oregon Clinical Translational Research Institute 
(OCTRI) outpatient clinic, the AIMS lab in Biomedical Engineering Dept at CHH1 or the Harold 
Schnitzer Diabetes Health Center. The participant will be sent the consent form prior to the 
screening by email so that they can have time to read it fully at their leisure and prepare any 

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questions they might have. Upon arrival and prior to any procedures, study staff will explain the 
study, give the participant ample time to ask questions and consider participation, and ensure that 
the participant voices understanding of the informed consent and study requirements. To 
minimize the possibility of coercion and to ensure that participant is signing the appropriate 
version of the consent, an informed consent checklist will be used by study staff. After the 
participant has signed the consent, a copy of the consent/authorization form will be given to the 
participant. The original will be kept for the source document.  
 
A capillary blood glucose (CBG) will be obtained and measured by a Contour Next glucose 
meter and recorded after consenting. Prior to measurement of any blood samples, the meter will 
undergo quality control testing with two different glucose levels, one high and one low, and both 
values must fall within the accepted range for a meter to be used.  
 
Study personnel will review medical history, and medications. Height, weight, pulse, and blood 
pressure will be obtained.  A study investigator will perform a physical examination, excluding 
breast and pelvic exams. Females of child-bearing potential will take a urine pregnancy test, 
which must be negative to participate.  A venous blood sample will be taken for the following 
tests: hemoglobin A1C, complete blood count, complete metabolic set (including creatinine, liver 
set, and electrolytes).  If the participant has already had these lab studies done within the past 2 
months and the results are available, those results can be used in place of the blood draw. An 
EKG will be completed. A study investigator will assess inclusion/exclusion criteria and review 
the participant’s medical record for clarification as needed.   When feasible, the participant’s 
insulin pump and glucose sensor, if applicable, will be downloaded before enrollment. A three-
digit participant ID number will be assigned to the participant.  This visit will take approximately 
1.5 hours.  
 
One Week Run-in Period 
The purpose of this run-in period is to teach participants how to use the Dexcom CGM system 
using the iPancreas software. For those new to CGM, it is also designed to provide them 
exposure prior to starting the intervention visits. The one week run-in period will take place 
within 8 weeks prior to the first 76 hour treatment visit.  After arrival at the OHSU OCTRI 
outpatient clinic, the AIMS lab in Biomedical Engineering Dept at CHH1 or Harold Schnitzer 
Diabetes Health Center clinic, women of childbearing potential will receive a urine pregnancy 
test if the last pregnancy test was more than 7 days prior.  This test must be negative before 
further participation is allowed. This visit will take approximately 30-60 minutes.  
 
Participants will receive training on how to use and calibrate the Dexcom G6 CGM system 
including changing out the sensor every 10 days.  The wire glucose sensor is sterile and 
commercially available from DexcomTM and will be used for single use only as directed by the 
manufacturer.  Participants will be trained to insert the sensor into the subcutaneous tissue of the 
abdomen after appropriate preparation of the abdominal skin per the manufacturer’s directions.  
Participants will be trained how to pair the Dexcom G6 transmitter to the iPancreas app on the 
smart phone, start and stop a new sensor session and how to enter calibrations. The Dexcom G6 
does not require calibrations. As part of the training, study staff will review with the participants 
that Dexcom G6 values can be inaccurate. In the event that the participant’s symptoms (such as 

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symptoms of hypoglycemia or hyperglycemia) are discrepant with the G6 CGM reading, then the 
participants will be instructed to perform a CBG and use this CBG value to make treatment 
decisions and use the CBG value to calibrate the Dexcom G6 device.  Participants will be 
provided with a copy of the Dexcom G6 user guide.    
 
The CGM alerts will be set at 70 mg/dL and 300 mg/dL. Participants will be trained how to 
begin a run-in study on the iPancreas app at home after two hours when the sensor warm-up is 
completed. Participants will be given a Dexcom G6 transmitter and sensor to insert the day 
before each treatment visit along with a Contour Next meter for measuring their capillary blood 
glucose.  
 
There is the option to complete this visit via Webex with the study devices delivered to the 
participant and study staff virtually connecting with participants for training on the devices and 
study procedures while they are at home. Participants will complete a urine pregnancy test at 
home provided by study staff if the last pregnancy test was more than 7 days prior. 
 
76 hour Treatment Visits  
The participant will be asked to check his/her glucose before driving to the clinic and to bring a 
snack in the car in case hypoglycemia does occur (in which case, the participant must park and 
treat the hypoglycemia).  After the first treatment visit, the washout period will be 6 days to 10 
weeks calculated from the day of admission to the research center until the start of the next 
admission.  The participant will arrive at the research center at approximately 7am.  Women of 
childbearing potential will receive a urine pregnancy test if the last pregnancy test was more than 
7 days prior.  This test must be negative before further participation is allowed 
 
An assessment will take place at the beginning of the participant’s first closed-loop study. We 
will inquire whether the participant has had changes in their medications and/or medical history 
to confirm the participant hasn’t developed any study exclusion criteria. A capillary blood 
glucose (CBG) will be obtained and measured by a Contour Next glucose meter.  When they 
arrive, participants will be given 15-20 grams of oral carbohydrate if the CBG reading is less 
than 70 mg/dl.  CBG values > 300 mg/dl will be managed at the discretion of the investigator 
with a correction bolus and serum ketones will be checked.  If serum ketones are ≥ 0. 6 mM, the 
study will not be started and insulin therapy will be guided by the onsite investigator.   
 
During each treatment visit, glucose will be controlled using either: 1) the OHSU MPC exercise-
enabled closed-loop mode or 2) the OHSU FMPD exercise-enabled closed-loop mode. The first 
12 hours of the visit will be conducted in the OCTRI inpatient research unit, the Harold 
Schnitzer Diabetes Health Center or the AIMS lab in the Biomedical Engineering Dept at CHH1.  
The participants will then go home. For the first 8 participants using the MPC mode, they will 
stay at OHSU during the day and go home at night, using the system in open-loop mode while 
off campus. If safety criteria are met, as outlined below, subsequent participants will be at home 
for the remainder of the intervention period, returning on Day 4 to the clinic to return all devices. 
A code team is available immediately by page at all times. 
 

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Inpatient Visits (~40 hours for first 8 participants, 12 hours for remainder of participants) 
An Omnipod (510K#042792) will be filled with Novolog® or Humalog® insulin for all studies. 
We will use only name brand insulin, not generic insulin. We will provide the participants with 
kits to replace the pod at home in case of pod malfunction or dislodgement at home. The 
Omnipod will be primed and inserted as directed by the manufacturer. Research staff will train 
participants on the approved pod placement options from the Omnipod User Guide. Participants 
will wear a Polar watch to inform the controller. Participants will disconnect his/her own pump 
and remove his/her own insulin infusion set once insulin delivery has started via the Omnipod. 
The research staff will initialize the system and begin the closed-loop study with the correct 
mode, either FMPD or MPC based on the participant’s randomization, using the iPancreas smart 
phone application. Two staff will review each of the settings to confirm the settings are inputted 
correctly. The participant will be given enough study supplies for the 76 hour visit.  A study 
investigator will be available in person or by phone for the entire 76 hour visit.  
 
Study staff will complete a training with each participant on using the Dexcom G6, the Omnipod 
system, and the Polar watch. Participants will be shown how to use the smartphone user interface 
which includes: entering basal profiles, insulin carb ratios and sensitivity, activating and 
deactivating Omnipods, giving meal boluses, carb treatments, blood glucose values and ketone 
levels, addressing alerts, troubleshooting the devices connection to the phone via Bluetooth, and 
pausing the study.   Instruction will be given on identifying an Omnipod malfunction. The time 
required for this training will vary, depending on the experience of each participant, but will be 
sufficient to help him/her become comfortable using the smart phone and changing the Omnipod. 
If the participant experiences difficulties using the Omnipod during the study period, study staff 
will be available to educate and support by phone. Training will include that the smart bolus 
calculator available in open loop mode is a suggestion and that participants should use their 
judgement on what insulin dose to take as the bolus calculator is not aware of certain 
circumstances such as illness or alcohol use.   
 
The participant will need to demonstrate competency in operating the system before study staff 
leave the room.  A competency assessment will be completed throughout the day of the first 
closed-loop visit. Each participant will start the G6 sensor and start the Omnipod on their own 
during onboarding. Participants will need to show competency in accepting exercise detection, 
entering fingerstick glucose values and announcing meals during the day on campus. Participants 
will demonstrate competency in the following using a simulated closed loop study: pausing and 
resuming a study, using the smart bolus calculator and manual bolus while in pause mode, for 
FMPD: force start exercise, cancel exercise, for MPC: disabling exercise adjustment. Participants 
will be given a pager number to call for any problems during the 76 hour visit. The companion 
will accompany the participant to receive training (or be previously trained) on treatment in case 
of severe hypoglycemia episode, including administration of rescue carbohydrates and use 
of emergency glucagon kit.  Companions will also be trained on the closed-loop system. This 
training may be completed virtually. 
 
The algorithm will push data up to a cloud server that can be monitored remotely every 5 
minutes. A study coordinator will be available at all times for the visits with the ability to 
monitor iPancreas remotely via a cloud system on the web in the event of any issues. iPancreas 

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will generate alerts on the smartphone according to Appendix D. The participants will all be 
trained as to the action required by each alert. Each alert has a specific condition to be met for it 
to be considered serviced (i.e. enter treatment with oral carbohydrates).  The refractory period is 
also specific to each alert with shorter refractory periods for alerts that concern participant safety.   
If the participant does not appropriately respond to the alert in the allotted timeframe, the alert 
will push to the study coordinator and the on-call investigator according to Appendix D. At that 
time, the coordinator will pull up the web-based monitoring system. The study investigator and 
technician may intervene with a telephone call, text or a personal visit at any time. If the 
participant cannot be reached and sensor glucose is below 50 mg/dl, the emergency contacts 
provided by the participant will be contacted. If the alert is still un-serviced and study staff are 
unable to reach the participant or either of the emergency contacts, emergency medical services 
will be contacted. To facilitate this, the phone will track the participant’s location and push GPS 
coordinates to the cloud server approximately every 10 minutes.  Cloud coordinates will be 
pushed with a known, fixed offset to allow for scrambling.  
 
In order to push alerts to study coordinators and study investigators, the cloud server used for 
remote monitoring will have a drop down menu for study staff to sign in and out for the duration 
of their monitoring shift.   Each study coordinator and investigator listed in the menu will have a 
cell phone number on file that can receive texts with pushed alerts.  
 
During all studies, sensed glucose data will be wirelessly transmitted via BTLE from the 
Dexcom G6 transmitter to the insulin-delivery algorithm every five minutes.  The insulin-
delivery algorithm will calculate insulin doses and will run on a smartphone. The smart phone 
will wirelessly communicate via BTLE to a PDM communicating to an Omnipod for automated 
insulin delivery.    
Both the FMPD and MPC control algorithms include a predictive low glucose suspend algorithm 
(PLGS).  The PLGS algorithm includes (1) an algorithm to predict hypoglycemia and (2) a 
mechanism to override the controller and shut off insulin if low glucose is predicted by the 
hypoglycemia prediction algorithm.  The predictive low glucose suspend algorithm will be 
continuously monitoring the trend of blood glucose with every new glucose value. If the sensed 
glucose is within 70-140 mg/dl and predicted to fall below 90 mg/dl within the next 30 minutes 
according to the LSTM algorithm, insulin infusion will be turned off.  If this occurs, the control 
algorithm will shut off insulin for a maximum of 120 minutes suspension within any 150 minute 
window. Suspension will be limited to 180 minutes during the nighttime (11pm-7am). After 5 
minutes of insulin suspension, insulin delivery will resume if sensor glucose is above 70 mg/dl 
and predicted to rise above 120 mg/dl at 30 minutes in the future. 
  
If at any time study staff determines that a sensor can no longer be used, a new sensor will be 
inserted. In order to ensure safety and to assess sensor accuracy, the participant will be asked to 
check their blood glucose two times during the day (typically before breakfast and at bedtime), 
for symptoms of hypoglycemia, and in response to system alert (such as for low or high sensor 
alerts).  We will also instruct patients to perform a capillary blood glucose immediately prior to 
and immediately following exercise. Participants will be instructed to check a fingerstick glucose 
at bedtime and again at 2am on exercise days. The participant will be able to check his/her 
capillary blood glucose more than 2 times a day if they feel they need to.  If the participant’s 

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blood glucose is < 70 mg/dl or is experiencing symptoms of hypoglycemia, he/she will be 
instructed to treat with 15 grams of carbohydrates.  
 
For participant safety, if a sensor value is not available for 20 minutes or communication with 
the Omnipod is lost for more than 30 minutes, the Omnipod will begin insulin delivery according 
to a pre-set basal profile(s) inputted for the participant at study start. When this occurs for a lost 
sensor, iPancreas will activate the predictive low glucose suspend feature if the last known 
sensor value was within the range of 70-140 mg/dl and predicted to fall below 90 mg/dl within 
thirty minutes or if the sensor glucose is less than 70 mg/dl. Insulin is suspended for 30 minutes, 
after which basal insulin delivery resumes. When communication with the sensor or Omnipod is 
restored, the system will automatically resume, updating the IOB accordingly.  
 
Participants will eat breakfast, lunch and dinner at approximately 8am, noon and 5pm 
respectively. Meals will be announced to the controller. For each meal, food items will be self-
selected. The number of grams of carbohydrates will be counted by the participant and entered in 
the controller. Immediately before eating, each participant will receive 100% (nominal) of 
his/her typical pre-meal insulin dose based on their insulin to carbohydrate ratio. The same self-
selected meals will be offered during FMPD Day 1 and MPC Day 3 inpatient days, and in the 
event a particular food item is not available, a different item with a similar amount of 
carbohydrate will be provided.  
 
Participants will perform activities of daily living (ADLs), such as vacuuming, washing dishes, 
and folding laundry for approximately 30 min at 10am or 3pm depending on the study (see 
‘Safety assessment – first 8 participants using MPC’).  Participants will complete a 30-minute 
aerobic exercise video at 10am or 3pm. (see ‘Safety assessment – first 8 participants using 
MPC’).  See Figure 3 below. 
Figure 3: Diagram of Exercise Study Procedures  
 
See Appendix E for Aerobic Video Outline. For participant safety, capillary blood glucose must 
be 80 mg/dl or higher to begin exercise.  

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During the exercise period, there will be defined rules for stopping exercise, including: 
• If the participant feels unwell, 
• If the participant develops hypoglycemic symptoms, such as excessive sweating, 
shaking/tremors, palpitations, feelings of dread or panic, light-headedness, nausea, 
difficulty concentrating or the like, 
• If the participant develops chest pain/pressure, 
• If the participant develops undue shortness of breath (SOB), 
• Signs of poor perfusion: light-headedness, confusion, ataxia, pallor, cyanosis, nausea, or 
cold and clammy skin  
• If the maximum heart rate of the participant (MHR) is exceeded, 
• For patient preference. 
If the exercise is stopped prematurely, the duration of exercise will be noted by the study staff 
and if the participant is deemed safe to participate in future studies, the exercise will be stopped 
after that same time duration for subsequent studies. For participant safety, if capillary blood 
glucose is < 70 mg/dl at any point during the exercise period, the participant will consume 15 g 
of carbohydrates and delay completion of exercise until blood glucose raises above 80 mg/dl. If 
glucose fails to rise above 80 mg/dl after a carbohydrate treatment during exercise, a second 
treatment of 15 grams will be given. Participants will be given instructions to take additional 
carbs at the start of exercise as needed based on CGM and trend to avoid post-exercise lows. See 
Appendix F inpatient instruction card. 
 
Participants will wear a Polar watch for collecting heart rate and accelerometry data. The Polar 
watch transmits this data to the smartphone controller via Bluetooth. iPancreas will convert the 
heart rate and accelerometry data into an estimated energy expenditure to determine if the 
participant is exercising. If the communication is not working between the Polar watch and the 
smartphone at the time of exercise during the inpatient visit, exercise may be delayed until 
communication is restored.  We are aware that there is a risk of hyperglycemia if the participant 
stops exercising after a short time with continued adjustments to insulin.  When using the FMPD 
mode: 1) an exercise cancellation option is available on the user interface for up to 30 minutes 
after the start of exercise that will revert insulin parameters to their nominal values and 2) if 
exercise is not detected by the algorithm when the participant is actually exercising, an exercise 
announcement button on the iPancreas user interface will be used. When using the MPD mode, 
the user can disable the exercise adjustment, thereby removing incoming exercise data for insulin 
dosing calculations.  
 
Safety assessment – first 8 participants using MPC  
Given this is the first human testing of the MPC exercise-enabled mode, the first 8 participants 
will stay at OHSU during the day for the entire period of using the MPC algorithm and go home 
to sleep each night (approximately 7pm-7am), using the system in open-loop mode while off 
campus. These participants will still complete only one in-clinic day for the FMPD arm (Day 1).  
 

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The study schedule will be slightly different for the days spent on campus using the MPC 
algorithm. On Day 1, participants will perform ADLs at 10am and again at 3pm. On Day 2, 
participants will complete the study aerobic exercise video at 10am and ADLs at 3pm. On Day 3, 
participants will perform ADLs at 10am and complete the study exercise video at 3pm. For each 
meal, food items will be self-selected. See Figure 3 above. 
 
For these 8 participants, we are matching Day 1 of the FMPD arm to Day 3 of the MPC arm. 
Participants will also perform the same activities at the same time on these days, ADLs at 10am 
and the study exercise video at 3pm. 
 
Capillary blood glucose will be measured with two consecutive blood glucose measurements at 
least 30 minutes apart prior to discharge. Participants will wait to discharge home at 
approximately 7pm if capillary blood glucose is <85 and or >300 mg/dl or at the discretion of the 
study investigator, and treatment will be at the discretion of the study investigator. Investigator 
will review the physician portal to assess participant’s insulin on board before they go home.  
These participants will use the system in open-loop mode while at home. Participants will be 
given a snack to take with them in case they develop hypoglycemia or hypoglycemic symptoms 
on the commute home.  
 
We will complete an interim analysis after the first 8 subjects using the MPC assessing time 
spent with CGM < 54 mg/dL, <70 mg/dL, and > 300 mg/dL and any adverse events. The MPC 
data will be compared to the equivalent data from the FMPD studies. If the interim analysis 
shows that the MPC data is comparable to the FMPD studies and presents no safety concerns, we 
will proceed to studying the MPC during outpatient visits. If it does not or if there are any 
instances of severe hypoglycemia or DKA (unrelated to infusion set failure), then the study will 
be halted, changes will be made as appropriate to algorithm and the protocol and a plan will be 
submitted to FDA and IRB that will need to be approved before further studies are conducted. 
After the algorithm adjustments are made, an additional 8 participants will then stay at the 
research clinic during the day for the entire period of using the MPC algorithm.  
 
The remainder of the participants using the MPC algorithm will be allowed to complete the study 
as an outpatient after the first approximately 12 hour study visit after 8 participants are deemed 
safe to sleep at home and successfully completed the MPC arm without any events of severe 
hypoglycemia or diabetic ketoacidosis. Severe hypoglycemia is defined as event that required the 
assistance of another person due to altered consciousness, and required another person to actively 
administer carbohydrate, glucagon, or other resuscitative actions. Diabetic ketoacidosis is 
classified as: symptoms such as polyuria, polydipsia, nausea, or vomiting, serum ketones >1.5 
mmol/L or moderate/large urine ketones, either arterial blood pH<7.3 or venous pH<7.24 or 
serum bicarbonate <15, and treatment provided in a health care facility. If an event of severe 
hypoglycemia or diabetic ketoacidosis should occur, the study will be halted and a description of 
the serious adverse event and a new risk mitigation plan will be submitted to the FDA. The study 
will only resume once FDA approval is received.     
 

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We are aware that there is a risk of severe hypoglycemia while the participants are at home. The 
system will alert if the sensed glucose values fall below 70 mg/dl prompting the participant to 
obtain a capillary blood glucose sample. Participants will be required to live with at least one 
other person age 18 or older and live within 40 miles of OHSU. All participants will provide two 
emergency contacts to study staff and will be given an emergency glucagon hypokit if they don’t 
already have one.  
 
In case of a system error that cannot be corrected immediately with the participant off campus, 
the participant will be able to go into open-loop mode. This will allow the Omnipod to begin 
basal insulin delivery for a pre-set basal profile(s) inputted for the participant at the study start. 
Participants will be able to give meal boluses and corrections through the Omnipod while in 
open-loop mode. When the error is resolved, the participant can resume closed-loop mode and 
the system will resume.  If the participant goes into open-loop mode, this will be visible on the 
cloud server and may prompt a telephone call from study staff to determine the issue and the best 
way to resolve it. The participant may contact study staff at any time during the outpatient 
portion of the visit.  
 
Discharge from inpatient clinic 
If the participant’s schedule does not allow them to return to the clinic before the 72 hour mark 
from the time the first pod was activated, then a new insulin pod will be placed as described 
above approximately 1-2 hours prior to discharge to avoid use of any single pod beyond 72 
hours. At the completion of the 12 hour inpatient visit, participants will be discharged from the 
clinic, with the exception of the first 8 participants using MPC exercise-enable mode, as detailed 
above. Capillary blood glucose will be measured prior to discharge. Participants will wait to 
discharge home if capillary blood glucose is <85 and or >300 mg/dl or at the discretion of the 
study investigator, and treatment will be at the discretion of the study investigator. Once 
participant’s capillary blood glucose is between 85-300 mg/dl, they can be discharged home. For 
all participants using the MPC mode, the investigator will review the physician portal to assess 
participant’s insulin on board before they go home. Participants will be given enough supplies to 
continue running the study while at home for 2 days. After the participant is discharged on Day 
1, he/she will return home for Day 2 and Day 3 and return to OHSU on the morning of Day 4 to 
return all devices and end the study.   Participants will be instructed to not eat a meal after he/she 
leaves the inpatient clinic after the Day 1 visit. Starting the morning of Day 2, participants will 
be instructed to eat meals and snacks as they normally would. Participants will be instructed that 
his/her companion will be required to stay with them each night while an outpatient. 
 
For the two days spent as an outpatient, participants will be asked to workout using the study 
video in the morning at a time of their choice on either Day 2 or Day 3. Participants will be 
asked to fill out the specifics of the exercise in a journal. Participants will be asked to not 
exercise on the other day spent at home. During the FMPD visit, participants will be instructed to 
only accept exercise detection on the app if they are exercising for 20 minutes or longer. 
Participants will be reminded to check their blood glucose before and after exercise (as soon as 
possible after exercise but no later than 15 minutes after the completion of exercise). For 
participant safety, capillary blood glucose must be 100 mg/dl or higher to begin exercise while 
the participant is at home. Participants will be given instructions to take additional carbs at the 

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start of exercise as needed based on CGM and trend to avoid post-exercise lows. See Appendix F 
outpatient instruction card. Participants will be required to have a person age 18 or older who 
attended a training session on the study present while the participant exercises at home. For at 
home exercise, the companion will stay after the exercise until the participant’s CBG is > 100 
mg/dl or for 60 minutes after exercise is completed, whichever is longer. Participants will inform 
study staff when exercising at home in the MPC arm to allow for more direct remote monitoring. 
Staff will continue to monitor until exercise is completed and glucose is above 100 mg/dL. 
 
Return to the Outpatient Clinic at OHSU 
On the fourth day, participants will return to the AIMS lab in Biomedical Engineering Dept at 
CHH1, the CTRC clinic, or the Harold Schnitzer Diabetes Health Center in the morning.  
Participants will be asked to arrive early enough to provide sufficient time to allow the pods to 
be removed before the 72 hour mark of pod use. The study will be terminated and the 
participant’s own insulin pump will be restarted. The study investigator will consult with the 
participant regarding appropriate insulin dosing for the remainder of the day. The Polar watch, 
Omnipod and Dexcom sensor will be removed from the participant. All infusion and sensor sites 
will be inspected for signs of irritation or infection. In addition, the sensor will be inspected for 
the possibility of breakage or fracture. If there is any evidence of sensor breakage, it will be 
recorded. If an area of inflammation of 1 cm or greater exists around the point of insertion, a de-
identified photograph will be taken of the area and the participant will return 1-3 days later for a 
follow-up visit. A capillary blood glucose value will be taken immediately prior to discharging 
the participant. Participants will be given oral carbohydrate for values below 85 mg/dl, and will 
be given an insulin bolus if deemed appropriate by the study investigator for values above 150 
mg/dl.  
There is the option to complete this visit by Webex. Participants will be given shipping boxes for 
sending all devices back.  Participants will connect with a study coordinator and investigator 
virtually to complete the visit.  
If a study visit is stopped prematurely, such as due to technical problems, the participant will be 
asked if they can repeat the study visit that was terminated early with additional compensation 
provided. Repeating the study visit will be optional. 
 
Hypoglycemia Treatment Guidelines 
 CBG < 70 mg/dl 
• Give 15 grams of oral carbohydrate.  
• Repeat treatment every 15 minutes as needed to raise blood glucose ≥70 mg/dl.   
Presence of STUPOR, LOSS OF CONSCIOUSNESS, or SEIZURE 
• Give 1 mg glucagon IM  
• Verify that insulin is turned off.  
• Further management per study investigator.  
Hyperglycemia Treatment Guidelines 
If the sensed glucose is ≥ 300 mg/dl, the participant will be instructed to check their blood 
glucose and to check the Omnipod for malfunction. This would include checking for insulin 

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leaks, making sure Omnipod is securely adhered to skin, and check for error messages on the 
phone running the algorithm.  
 
If capillary blood glucose value is over 300 mg/dl for more than 2 hours or is ≥ 400 mg/dl at any 
time, the participant will be instructed to check serum ketones using the Abbott Precision Xtra 
meter and to change out the Omnipod. If serum ketones are over 0.6 mM, the on-call study 
investigator will be alerted to discuss proper management, including delivering a correction 
bolus. In addition, the participant will be encouraged to drink sugar-free liquids. If serum ketones 
are above 1.5 mM at any time, the study will be stopped and insulin will be administered as 
directed by the on call investigator.  
 
Cleaning and Disinfecting  
All devices will be cleaned and disinfected between participants.  The smart phone, Dexcom G6 
transmitter, heart rate monitor and Omnipod PDMs are cleaned by study staff.   Technicians who 
are disinfecting units will wash hands thoroughly and wear gloves.   All items will undergo 
intermediate-level disinfection using Oxivir TB disposable wipes.  The disinfectant will be 
applied and allowed to air dry. After disinfection, when the units are completely dry, they will be 
placed in a sealed bag labeled with participant information.  
 
Stopping Rules 
Individual study stopping rules 
The closed-loop study will be stopped and open-loop control will be resumed under the guidance 
of the on call study investigator if any of the following occur after the start of the study: 1) 
capillary blood glucose falls to < 40 mg/dl at any time point, 2) capillary blood glucose exceeds 
400 mg/dl on two occasions (120 min or more apart within a 4 hour window), 3) capillary blood 
glucose exceeds 400 mg/dl on two occasions more than 120 minutes apart but outside of the 4 
hour window and during that time, the capillary blood glucose has not fallen below 250 mg/dl, 4) 
serum ketones are above 1.5 mM at any time, 5) seizure or unconsciousness associated with 
hypoglycemia.  
 
Entire study stopping rules 
Triggers for reporting unanticipated problems are seizure, hospitalization, death or any other 
occurrence considered serious by the PI and Medical Monitor. If any studies are stopped for 
severe hypoglycemia or diabetic ketoacidosis, then the entire study will be halted. Severe 
hypoglycemia is defined as event that required the assistance of another person due to altered 
consciousness, and required another person to actively administer carbohydrate, glucagon, or 
other resuscitative actions. Diabetic ketoacidosis is classified as: symptoms such as polyuria, 
polydipsia, nausea, or vomiting, serum ketones >1.5 mmol/L or moderate/large urine ketones, 
either arterial blood pH<7.3 or venous pH<7.24 or serum bicarbonate <15, and treatment 
provided in a health care facility. If an event of severe hypoglycemia or diabetic ketoacidosis 
should occur, the study will be halted and a description of the serious adverse event and a new 
risk mitigation plan will be submitted to the FDA. The study will only resume once FDA 
approval is received. In addition, if there is any unexpected event such as death or patient 
hospitalization, the studies will be stopped until the root cause is evaluated. 

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The Fading Memory Proportional Derivative (FMPD) Algorithm 
The FMPD algorithm determines insulin delivery rates based on proportional error, defined as 
the difference between the current glucose level and the target level, and the derivative error, 
defined as the rate of change of the glucose. Each of these errors is calculated over a time 
interval. The “fading memory” designation refers to weighting recent errors more heavily than 
remote errors. This weighting provides an adaptive component to the algorithm. In simple terms, 
the insulin rate is increased for high or rising glucose levels. Gain factors determine the degree to 
which proportional or derivative errors lead to changes in the delivery rate.  
 
For the FMPD exercise-enabled mode, the exercise threshold will be set to 4 METs/min for 
every participant at the start of the study. If the corrected MET value is greater than 4 METs for 
a period of 5 consecutive minutes during the first exercise period, exercise is considered to be 
ongoing.  An exercise dosing adjustment algorithm will be used when exercise is detected that 
has been previously tested and published.  When exercise is detected while in the FMPD 
exercise-enabled mode, and the participant confirms he/she is exercising, insulin will be turned 
off for 30 minutes (nominal) immediately after detection of exercise. Subsequently, the insulin 
infusion rate will be reduced to 50% (nominal) for a period of 1 hour (nominal). The exercise 
detection algorithm will prompt the participant if exercise is occurring prior to adjusting dosing.  
For example, if the participant’s METs exceed a threshold of 4 METs, the AP will detect this and 
ask the participant if they are exercising.  If the participant acknowledges this and says “Yes”, 
the AP will adjust the dosing.  If the participant selects that they are not exercising, iPancreas 
will present a dropdown menu from which the participant can select their current activity for 
logging purposes (e. g. housework).  It will also present several choices for the amount of time 
that exercise detection will be suspended so that the participant will not continuously receive 
detection alerts during that activity (15, 30 or 60 minute suspension).  If the participant says 
“No”, this is considered a false alert because the algorithm has detected exercise, but the 
participant was not actually exercising.  Because these false alerts can be annoying to the 
participants, the AP includes an adjustable exercise detection threshold.  The adjustable exercise 
detection threshold works as follows:  
At the start of the study, the participants’ exercise detection threshold will be set to 4 METs. 
• On the first day of the study, when the participant exercises at the hospital, the AP 
records the participants’ METs during exercise and also records the participants’ METs 
during activities of daily living and other non-exercise events.   
• Based on data from this controlled setting, a “lower bound MET” for that participant will 
be calculated based on a lower-bound confidence interval set around their METs recorded 
during exercise. 
• If that participants’ lower bound MET during exercise is greater than 4, their maximum 
allowable exercise threshold value (MAETV) will be set to the lower bound MET.  
Otherwise, the MAETV will remain at 4. 
• Every time a false alert occurs for detecting exercise, the participants’ exercise detection 
threshold will increase by 0.25 MET.  However, the exercise detection threshold will 
never exceed the MAETV described above.  
The Model Predictive Control (MPC) Algorithm 

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Our MPC algorithm uses a glucoregulatory model to predict glucose outcomes over a predicted 
horizon (Np), and mathematically solve for the optimal insulin doses across the control horizon 
(Nc) to bring the participant to target. The model is updated at each timestep by a Kalman filter, 
which uses the difference between CGM observations and model predictions to update the 
physiologic model states.  In short, a model-predictive controller uses a physiologic model to 
calculate how much insulin is required to bring someone to glucose target, and these predictions 
are adapted to the specific participant using a Kalman filter.  
 
For the MPC exercise-enabled mode, there is a model within the controller that takes as an input 
the aerobic metabolic expenditure in addition to the CGM and meal inputs.  The algorithm uses 
heart rate and accelerometer data collected on the patient’s body to calculate metabolic 
expenditure.  The metabolic expenditure then acts on the model for the insulin dynamics, 
whereby more energy expenditure and longer duration exercise can lead to a more substantial 
effect of insulin on the CGM (i.e. the CGM will drop more in response to more intense aerobic 
exercise and with longer duration exercise).  In this way, the model within the MPC control 
algorithm is always aware of exercise as a continuous input to the system and can respond 
dynamically to short or long, light, moderate, or intense exercise bouts.  We expect that the MPC 
controller will be able to dynamically adapt to either short or long exercise bouts.  We also 
expect the MPC to dynamically adapt to in-home exercise better, which can be more variable 
than static exercise that is performed within a clinic under controlled conditions.  
Since the MPC mode treats exercise differently than the FMPD mode, some exercise alerts to the 
user will not populate.  The low glucose alert will populate when sensor glucose goes below 70 
mg/dl, instead of 85 mg/dl in FMPD mode with exercise detection.  The alert not allowing 
exercise when ketones are above 0.6 mM will not populate while in MPC mode, but the 
participants will be coached not to exercise when ketones are high.  
Statistical methods 
The primary study endpoint is percent of time with glucose sensor <70 mg/dL during the 
inpatient clinic day. The hypothesis to be tested is the MPC exercise-enabled closed-loop system 
will increase time in range as compared to the FMPD exercise-enabled closed-loop system. As 
our main approach, we will perform a two-sided Wilcoxon test for the paired differences. This 
test is widely used and easily interpreted. However, it cannot accommodate missing data or 
estimate crossover effects, and while we do not anticipate that these will affect our study 
outcomes, we plan to conduct a supplemental analysis using a linear regression model with 
bootstrapped standard errors, which do not require distributional assumptions. In resampling for 
the bootstrap, we will use study subjects as the sampling unit to account for correlation between 
their repeated observations. The general model is as follows:  
(1)  
𝑌𝑖𝑗= 𝛽0 + 𝛽1𝑇𝑟𝑡𝑗+ 𝛽2𝑆𝑒𝑞𝑖+ 𝛽3𝑃𝑒𝑟𝑖𝑜𝑑𝑗 
In this model, the outcome Yij is the percent of time with glucose sensor <70 mg/dL for person i 
in observation period j. Trtj represents the treatment arm (MPC=1, FMPD=0). Seqi is an indicator 
for sequence (AB vs BA) and Periodj indicates when Trtj occurred in the sequence. The 
coefficient β0 represents the mean response for FMPD, and the coefficient β1 represents the 
difference between treatments to be tested. The coefficients β2 and β3, mean differences for 
sequence or period, are both expected to equal zero; a large effect or significance test with p-
value <0.05 will be considered evidence of a carryover effect. Hypothesis tests will be two-sided 
with type I error set to 0.05. Because statistical tests are specified and prioritized a priori and our 

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proposed endpoints are highly related, we will follow recommendations to report p-values and 
confidence intervals rather than adjust for multiple comparisons. 
Model fit and alternatives: Goodness of fit statistics and model fitting diagnostics will be used to 
assess for influential points and to evaluate alternative model specifications. If needed to 
compensate for some skew and heteroscedasticity in secondary outcomes, we will use 
bootstrapped variance estimators and compare these against robust estimates.  
Missing data: Our primary approach will include all available data as an intention-to-treat 
analysis, regardless of whether study subjects completed both arms. An observation will be 
included if at least 24 hours of data are available. However, we expect very low levels of 
missingness; in our previous four-arm crossover study, only one subject withdrew before 
completing at least two arms. Dropped CGM values will be interpolated over short time periods, 
using capillary values for calibration when available. In the event of ≥10% missingness in either 
subject data or CGM values, we will analyze outcomes under multiple imputation to compensate 
for potential bias. 
Additional considerations for selected secondary endpoints: The number of carbohydrate 
treatments will be modeled using model (1) above with Poisson regression for count data. The 
coefficient of variation of glucose is non-normal without an obvious probability distribution, so 
that bootstrapping will be our primary approach for this endpoint. Data for percent of time with 
sensed glucose <54 mg/dl may be sparse; if so, we will present counts of events where glucose 
went below this level, counting as separate events when the time between them is ≥ 30 minutes.   
Confidentiality and Protection of Human Participants 
RISKS and BENEFITS 
Risks: The risks of the protocol procedures are considered minor. Nonetheless, since pumps and 
sensors used within automated glucose control systems are imperfect, there is a risk for 
hyperglycemia and hypoglycemia. All studies will issue alerts and will be remote monitored 
during each visit with unserviced alerts being pushed to the study coordinator and investigator. A 
study investigator will be on call at all times.  
Risks from exercise include falls, sprains, bruises, very low risk of bone fractures and head 
trauma. The likelihood of significant harm is quite low.  
Rarely, there can be allergic responses to insulin, such as skin redness, hives, itching of the skin, 
swelling of the mouth, or breathing difficulties. These reactions are considered very unlikely. 
The following events have been identified as possible anticipated device-related adverse events 
of Dexcom G6 sensor insertion and wear: 
• Excessive pain or discomfort from either system deployment or during wear period (8 or 
greater on a 10-point Likert scale)  
• Excessive bleeding, defined as requires removal of the device to stop bleeding 
• Hematoma, defined as induration at the sensor insertion location (ecchymosis is a known 
consequence of needle skin puncture or pressure from sensor pod and will not be captured 
as an AE) 
• Edema from sensor and/or adhesive tape that is significant and non-resolving within 48 
hours of sensor pod removal 
• Erythema from sensor and/or adhesive tape that is significant and non-resolving within 48 
hours of sensor pod removal 

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• Local infection, defined as presence of pus at either sensor wire or sensor pod site  
• Sensor or introducer needle fracture during insertion/wear/removal For this reason, the 
study investigator will inspect each removed sensor for the possibility of breakage or 
fracture. Any evidence of sensor breakage will be recorded and reported to FDA and the 
sensor company. 
 
Benefits: The participant may not directly benefit from being in this study; however, their 
participation may help to advance automated insulin delivery technology. 
 
COSTS:   
The participants who stay in clinic each day for the MPC arm will receive $1025. If a participant 
withdraws early from the study, compensation will be given as follows: $50 for run-in, $225 per 
in clinic day for the MPC arm, $300 for the FMPD arm.  
Otherwise, participants will receive $650 for completion of all study visits.  If a participant 
withdraws early from the study, compensation will be given as follows: $50 for run-in, $300 for 
the MPC arm and $300 for the FMPD arm. There is no compensation for the screening visit. If a 
participant is asked to repeat a study due to technical problems, he/she will receive an additional 
$300.    
 
Monitoring Entity: 
This investigation will be monitored by the co- investigator Leah Wilson MD. Dr. Wilson has no 
commercial interest in any of the companies which manufacture any of the devices used in this 
study. Drs. Jessica Castle, Peter Jacobs and Joseph El Youssef are inventors on patents regarding 
the algorithms. 
 
Data Collection: 
Participant privacy will be protected by using a three-digit identifying number to code study 
documents. All paper source documents will be kept in a locked cabinet for a minimum of five 
years. All data from the study files on the smart phone master controller will subsequently be 
entered into the authorized electronic OCTRI Cloud database.  
 
Recording of Data: 
Investigators and staff will record data collected during the clinical trial on the CRF’s. The CRFs 
will include: 
1. Screening form 
2. Dexcom G6 Training Visit 
3. iPancreas Training 
4. Companion Training 
5. Day 1 Inpatient MPC Closed-loop Study Visit  
6. Day 2 Inpatient MPC Closed-loop Study Visit 
7. Day 3 Inpatient MPC Closed-loop Study Visit 
8. Day 1 Inpatient FMPD Closed-loop Study Visit 
9. Day 4 MPC Closed-loop Study Visit  

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10. Day 4 FMPD Closed-loop Study Visit 
11. Phone Update Form 
12. Adverse Event form 
13. Serious Adverse Event form 
14. Concomitant Medications 
 
The Principal Investigators may authorize other personnel to make entries in the CRF. The coded 
data collected during this study will be used for analysis of the primary and secondary endpoints 
listed in this protocol. The key to the code for this study will not be stored in the repository and 
only named study members on this project will have access to the key for this study. Researchers 
who request data from the repository will not receive any identifiers aside from date and we do 
not anticipate that the date will allow those researchers to re-identify the data. However, some of 
the researchers named on this project may use the data from the repository which would mean 
that the repository data will still be potentially identifiable to those who have access to the key as 
part of this project. The coded data will also be stored in the OregonAPC repository according to 
IRB protocol 19858.  During screening, all new participants will sign the consent form to store 
their study data in the data repository. The data to be collected includes: 1) glucose sensor data, 
2) blood glucose data, 3) insulin data, 4) physical activity data, and 5) food and exercise data. All 
data, except for blood glucose, is aggregated by the iPancreas app. The blood glucose data is 
collected through downloading the Contour Next BG meters and exporting data as an excel file. 
There are no biological specimens collected during this study. 
 
 
Monitoring Procedures: 
This protocol is written in accordance with the principles established by the 18th World Medical 
Assembly General Assembly (Helsinki, 1964) and amendments and clarifications adopted by the 
29th (Tokyo, 1975), 35th (Venice, 1983), 41st (Hong Kong, 1989), 48th (Somerset West, South 
Africa, 1996), 52nd (Edinburgh, 2000), 53rd (Washington, 2002), 55th (Tokyo, 2004), 59th 
(Seoul, 2008), and 64th (Brazil, 2013) General Assemblies. The investigator will ensure that the 
study described in this protocol is conducted in full conformance with those principles, the 
protocol, current FDA regulations, ICH Good Clinical Practices (GCP) guidelines, Good 
Laboratory Practices (GLP) guidelines, local ethical and regulatory requirements, including the 
Federal Food, Drug and Cosmetic Act, U.S. applicable Code of Federal Regulations (title 21), 
any IEC requirements relative to clinical studies.  
Should a conflict arise, the investigator will follow whichever law or guideline affords the 
greater protection to the individual participant. The investigator will also ensure thorough 
familiarity with the appropriate use and potential risks of use of the study device, as described in 
this protocol, prior to the initiation of the study. 
 
Adverse Event Reporting 
At all study visits, study staff will determine if any adverse events (AEs) have occurred. Disease 
related events that are chronic in nature and occur as part of the progression of the diabetes disease 
state (i.e. diagnoses of retinopathy, nephropathy, and neuropathy) will not be captured as adverse 
events in this study. Hypo- and hyperglycemia will not be considered AEs unless participant has 

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positive ketones or displays symptoms of hypoglycemia such as: loss of consciousness, slurred 
speech, hospitalization or EMS services called.   
One of the investigators will write up a description of the adverse event/unanticipated problem. 
All reportable new information (RNI) will be reported to the IRB within five calendar days after 
the PI learns of the event. RNI is any information that might meet the regulatory definition of an 
unanticipated problem involving risks to subjects or others or serious or continuing noncompliance 
that might impact the criteria for IRB approval. The report will be submitted to the IRB by the 
principal investigator or study coordinator. A summary of all UP's and adverse events, including 
those that do not meet the requirement for RNI, will be submitted with the continuing review. All 
AEs will be monitored until adequately resolved or stable. Information regarding AEs that occur 
during the study will be entered into appropriate CRFs. Such information will include, at a 
minimum: 
• Date of event 
• Severity 
• Outcome 
• Resolution of event 
 
Definition of Adverse Event 
An AE is any clinically significant undesirable experience (sign, symptom, illness, or other 
medical event) meeting the causality definition above that appears or worsens in a participant 
during a clinical study. A clinically significant event is any event (sign, symptom, lab/imaging 
abnormality, or diagnosis) that is noteworthy enough to merit documentation in standard medical 
records (e.g. history and physical, progress notes, clinic visit notes, etc.). Other non-clinically 
significant events (e.g. colds, minor headaches, etc.) may be documented on the comments CRF. 
Mild hypoglycemia is expected in persons with diabetes using insulin and are typically self-
limiting in nature; thus, this will not be captured as an AE. The Medical Monitor will have the 
final say in determining the causality. Adverse events that continue after the participant’s 
discontinuation or completion of the study will be followed until their medical outcome is 
determined or until no further change in the condition is expected. 
 
Serious Adverse Events  
A serious adverse event (SAE) is defined as any untoward medical occurrence that: 
• Results in death 
• Is life-threatening; (substantial risk of dying at the time of the adverse event or suspicion 
that continued use of the device would result in a participant’s death  
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity or substantial disruption of the 
ability to conduct normal life functions  
• Requires medical or surgical intervention to prevent permanent impairment or damage.  
Exceptions to the SAE definition will include the following: 
• Elective surgery 

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• A planned hospitalization for pre-existing condition, without a serious deterioration in 
health 
Any SAE, including death, due to any cause (related or unrelated to the device), that may occur 
during a clinical study will be reported to the PI and Medical Monitor immediately (within 1 
working day of learning of the event).  
 
Severity of Adverse Events  
The following definitions may be used to rate severity of AEs: 
• Mild 
Awareness of signs or symptoms, but easily tolerated; are of minor irritant type that is 
outside the norm for the disease state or subject; causing no loss of time from normal 
activities; symptoms would not require medication or a medical evaluation; signs and 
symptoms are transient. Mild hypoglycemia is expected in diabetes and will not be 
captured as an AE.   
Example: ketosis not requiring an ER visit. 
• Moderate 
Discomfort severe enough to cause interference with usual activities, requiring treatment 
due to cognitive impairment, by family member or emergency personnel  
Example: hypoglycemia with inability to self-treat, requiring third party assistance for 
treatment and/or an emergency room visit. 
• Severe 
Incapacitating, causing inability to do work or usual activities; signs and symptoms may 
be of systemic nature or require medical evaluation and/or treatment at a health care 
facility 
Example: hypoglycemia with loss of consciousness or seizure involvement 
Relationship of Adverse Events to Study or Study Device 
The investigator will categorize the relationship of the event to the study or study device as 
follows:  
• Not Related 
AE is due to an underlying disease state or concomitant medication or therapy not related 
to the device, disease or study. 
• Unlikely Related 
AE has minimum or no temporal relationship to the study device, disease or study 
participation and/or a more likely alternative etiology exists. 
• Possibly Related 
AE has a strong temporal relationship to the study device, disease or study procedures 
and alternative etiology is equally or less likely compared to the potential relationship to 
the device, disease or study. 
• Probably Related 

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AE has a strong temporal relationship to the study device, disease or study and another 
etiology is unlikely. 
• Definitely Related 
AE has a strong temporal relationship to the study device, study procedures or disease 
and another etiology does not exist. 
Unanticipated Problems 
Unanticipated problems, including study, disease or device-related problems will be detected by 
reviewing descriptions of known or foreseeable adverse events and risks in the IRB-approved 
research protocol and the current IRB approved consent form, any underlying disease or 
conditions of the subject experiencing the adverse event, a careful assessment of whether the 
adverse event is related or possibly related to the subject’s participation in the study or if root 
cause or associations is with study devices.  
 
Unanticipated Adverse Device Effect (UADE) 
An unanticipated adverse device effect (UADE) is not expected to occur. An UADE is defined as 
any serious adverse effect on health or safety or any life-threatening problem or death caused by 
– or associated with – the device, if that effect, problem, or death was not previously identified in 
nature, severity, or degree of incidence in the investigational plan (including documents such as 
the protocol, the informed consent document, other study-related documents), or any other 
unanticipated serious problem associated with the device that relates to the rights, safety, or 
welfare of participants.   
During the review of a reported SAE, if the PI and Medical Monitor input determines the 
severity or extent of the event was not cited in this protocol or associated protocol materials, and 
the event was classified as, ‘possibly related’ to the device, the event will be documented as an 
UADE. If the event is classified as an UADE, the Investigator must notify the IRB and Dexcom 
will notify the FDA within ten (10) working days of the original SAE notification. 
If determined that the UADE presents an unreasonable risk to participants, we will terminate all 
investigations or parts of investigations presenting that risk as soon as possible, but not later than 
5 working days after such determination is made and not later than 15 working days after we first 
receives notice of the original SAE. We will not resume a terminated study without IRB and 
FDA approval. 
 
MDR Reportable Events/MDR Reporting 
A device issue, whether related to a complaint or not, is an allegation from the participant or 
study personnel regarding an indication of the failure of a device to meet user expectations for 
quality or performance specifications. Device issues will be recorded onto appropriate CRFs by 
site personnel. The CGM and Omnipod devices are currently marketed. Therefore, the PI will 
follow the required reporting regulations to Dexcom or Insulet if an MDR reportable event 
occurs.   
MDR reportable events are events that manufacturers become aware of that reasonably suggest 
one of their marketed devices may have caused or contributed to a death or serious injury, or has 
malfunctioned and the malfunction of the device would likely cause or contribute to a death or 
serious injury if the malfunction were to recur (21 CFR 803.3). 

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Confidentiality Procedures: 
To protect confidentiality, standard institutional practices will be followed as described in the 
OHSU Information Security and Research Data Resource Guide 
(http://ozone.ohsu.edu/cc/sec/isg/res_sec.pdf) to maintain the confidentiality and security of data 
collected in this study. Study staff will be trained regarding these procedures. See IRB protocol 
19858 for a complete description of the confidentiality and security of the study data collected 
during this study to be stored in the OregonAPC repository.  
Data for this project will be stored in OCTRI's installation of REDCap, a highly secure and 
robust web-based research data collection and management system. Features of REDCap that 
protect participants' privacy and data security include: 
• Physical Security: OCTRI's REDCap software is housed on servers located in ITG's 
Advanced Computing Center providing locked physical security. 
• Electronic Security: The REDCap servers are housed behind both the OHSU firewall and 
a second ACC firewall.  All transmissions of data from the application are encrypted over 
HTTPS with the industry standard TLS 1.1 protocol (AES 256-bit encryption).  
• Controlled User Access: REDCap is employs a robust multi-level security system that 
enables researchers to easily implement "minimum necessary" data access for their 
research staff, including specification of data fields that are identifiers. This feature 
includes “single click” ability to provide completely deidentified (removing all identified 
data fields and shifting dates) for analysis or other purposes.  User activities are logged to 
enable auditing of all data access.   Access is integrated with OHSU's network such that 
users who are also OHSU employees are authenticated against their OHSU network 
credentials.   
• Data Integrity: REDCap is jointly managed in accordance with OHSU Information 
Security Directives by ACC staff and members of OCTRI's Biomedical Informatics 
Program, ensuring fidelity of database configuration and back-ups.  User activities are 
logged to enable auditing of all data changes. 
Paper files will be stored in locked filing cabinets in restricted access offices at OHSU. After the 
study, source documents will be maintained at the participating clinical center (or offsite record 
storage facilities) 2 years after a marketing application is approved for our group's decision 
support device or discontinuance of pursuit of marketing approval.   
 
 
 
 
 
 
 
 
 

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Appendix A: Physical Activity Readiness Questionnaire 
 
 

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Appendix B: Devices 
Insulet Omnipod insulin management system which includes PDM and Omnipod 
 
 
Dexcom G6 Continuous Glucose Monitoring System which includes Sensor and Sensor 
Transmitter  
 
 
 
 
 
 
 
 
 
 

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Contour Next Blood Glucose Meter 
Abbott Precision Xtra Meter 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix C: Hypoglycemia Awareness questionnaire: This survey item will be used to 
categorize awareness or having reduced awareness of hypoglycemia. 
 
1. Check the category that best describes you: (check one only) 
 
 I always have symptoms when my blood sugar is low (A) 
 I sometimes have symptoms when my blood sugar is low (R) 
 I no longer have symptoms when my blood sugar is low (R) 
2. Have you lost some of the symptoms that used to occur when your blood sugar was low? 
 
 Yes (R) 
 No (A) 
3. In the past 6 months how often have you had moderate hypoglycemia episodes? (Episodes 
where you might feel confused, disoriented, or lethargic and were unable to treat yourself). 
 
 Never (A) 
 Once or twice (R) 
 Every other month (R) 
 Once a month (R) 
 More than once a month (R) 
4. In the past year, how often have you had severe hypoglycemia episodes? (Episodes where you 
were unconscious or had a seizure and needed glucagon or intravenous glucose?) 
 
 Never (A) 
 1 time (R) 
 2 times (R) 
 3 times (R) 
 4 times (R) 
 5 times (R) 
 6 times (R) 
 7 times (R) 
 8 times (R) 
 9 times (R) 
 10 times (R) 
 11 times (R) 
 12 or more times (R) 
 

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5. How often in the last month have you had readings < 70 mg/dl with symptoms?  
 
 Never 
 1 to 3 times 
 1 time/week 
 2 to 3 times/week 
 4 to 5 times/week 
 Almost daily 
6. How often in the last month have you had readings < 70 mgdl, without symptoms? R: 5<6, A: 
6<5; 
 
 Never 
 1 to 3 times 
 1 time/week 
 2 to 3 times/week 
 4 to 5 times/week 
 Almost daily 
7. How low does your blood sugar need to go before you feel symptoms? 
 
 60-69 mg/dl (A) 
 50-59 mg/dl (A) 
 40-49 mg/dl (R)  
 < 40 mg/dl (R) 
 
8. To what extent can you tell by your symptoms that your blood sugar is low? 
 
 Never (R) 
 Rarely (R) 
 Sometimes (R) 
 Often (A) 
 Always (A) 
 
 
 
 

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Appendix D: Alert Manager Specifications 
 
# 
NAME: Activation 
criteria 
Clearing Criteria 
Algorithm 
specifics 
Notification to 
participant 
Re-fire 
Time 
(min) 
Refractory 
Period (min) 
Coordinator 
push 
Investigator 
push 
Waiting period 
4 
cbg_equal_or_under_
40: CBG ≤ 40 mg/dl 
AND alert 4 not active  
User enters CBG > 40 
mg/dL after 15 
minutes. Once rescue 
carb are entered, the 
waiting period starts. 
   If CBG ≥70 at any 
time, alert clears. 
None 
 "Blood glucose is 
below 40 mg/dl. 
Please take 30 gm of 
rescue carbohydrates 
and recheck your 
blood glucose level in 
15 minutes." 
5 
- 
Immediately 
Immediately 
Waiting period 
ends when alert
13 is serviced 
OR clear criteri
is met 
5 
cbg_under_70: CBG < 
70 mg/dl AND alert 5 
not active AND alert 4 
not active 
CBG entry ≥70 clears 
alert.  
 Once rescue carbs are 
entered, the waiting 
period starts. 
Alert clears if 
activation of alert 4 is 
met 
None 
"Blood glucose is 
below 70 mg/dl. 
Please take 15 gm of 
rescue carbohydrates 
and recheck your 
blood glucose level in 
15 minutes." 
15 
- 
After 1st re-
fire 
After 2nd re-
fire 
Waiting period 
ends when alert
13 is serviced 
OR clear criteri
is met 
6 
sensor_glucose_low: 
Sensor glucose < 
LOW_THRESH AND 
alert 4 AND alert 5 
AND alert 6 not active 
or refractory & no CBG 
within last 15 minutes 
CBG check 
OR sensor ≥ 
LOW_THRESH 
For MPC, 
LOW_TH
RESH = 70 
mg/dL 
 
For FMPD, 
when not in 
exercise 
mode, 
LOW_TH
RESH = 70 
mg/dL 
 
"Sensor glucose is 
below 
LOW_THRESH 
mg/dl. Please perform 
a blood glucose check 
now." 
15 
60 
After 1st re-
fire 
After 2nd re-
fire 
- 

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For FMPD 
when in 
exercise 
mode, 
LOW_TH
RESH = 85 
mg/dL 
 
 
7 
cbg_equal_or_over_30
0: CBG ≥ 300 mg/dl 
AND alert 27 not active 
or refractory AND alert 
7 not active or 
refractory 
Ketone check 
None 
"Blood glucose is 
above 300 mg/dl. 
Please check the 
insulin pod for leaking 
or detachment and 
check ketone levels 
now." 
30 
120 
After 1st re-
fire 
After 2nd re-
fire 
- 
8 
sensor_glucose_high: 
Sensor glucose ≥ 300 
mg/dl for 30 minutes 
within the last 45 
minute period AND 
alert 8 AND alert 7 
AND alert 27 not active 
or refractory AND no 
CBG in last 30 minutes 
CBG check. 
OR sensor < 300 
None 
"Sensor glucose is 
over 300 mg/dl. Please 
perform a blood 
glucose check now." 
30 
60 
After 1st re-
fire 
After 2nd re-
fire 
- 
10 
Insulin_meal_bolus_fa
ilure: If 50% of meal 
bolus is still not 
delivered after 20 
minutes. 
Auto clears  
None 
Insulin bolus failed to 
deliver, please contact 
the study investigator.  
- 
- 
Immediately 
Immediately 
- 
13 
recheck_cbg: Alert 4 
OR alert 5 in waiting 
period for 15 minutes  
CBG recheck 
 
"Please perform a 
blood glucose check 
now." 
20 
- 
After 1st re-
fire 
After 2nd re-
fire 
- 
14 
no_data_connection: 
No connection to the 
internet or data for 40 
minutes 
Phone connects to a 
wifi network or regain 
cell service 
 
There is no connection 
of the phone to the 
internet. Please move 
back into cell phone or 
wifi range.  
40 
- 
- 
- 
- 

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17 
transmitter_not_repor
ting: Sensor is out of 
date for > 20 minutes 
AND alert 17 AND 
alert 18 AND alert 20 
not active or refractory 
Clears with valid 
sensor 
 
"A sensor reading has 
not been received in 
the last 20 minutes. 
Please ensure that the 
phone is within range 
of the sensor." 
20 
- 
After 1st re-
fire 
After 2nd re-
fire 
- 
18 
replace_transmitter: 
iPancreas sends 
message to replace the 
transmitter immediately 
60 minutes after 
activation criteria for 
alert 17 if clear criteria 
has not been met 
User 
acknowledgement 
 
"The transmitter is no 
longer functional. 
Please replace it 
immediately." 
- 
120 
- 
- 
- 
19 
sensor_glucose_invali
d: Sensor value is 
invalid for > 20  
Minutes AND alert 19 
AND alert 18 AND 
alert 20 not active or 
refractory 
Clears with valid 
sensor 
 
"Sensor value is not 
reporting correctly. 
Please check your 
sensor site for 
problems. Contact the 
study coordinator if 
needed." 
20 
- 
After 1st re-
fire 
After 2nd re-
fire 
- 
20 
replace_sensor: 
iPancreas sends 
message to replace the 
sensor immediately 60 
minutes after activation 
criteria for 19 if clear 
criteria has not been 
met  
User 
acknowledgement 
 
"The sensor may no 
longer be functioning. 
Please replace it 
immediately." 
- 
120 
- 
- 
- 
21 
Insulin_pump_commu
nication_failure: Basal 
Insulin Fails to deliver 
correct amount for 60 
minutes OR insulin 
suspend required and 
no connection to pump 
Successful basal 
insulin is 
delivered  OR insulin 
is successfully 
suspended 
 
“Insulin 
communication 
failure. Please move 
PDM and POD closer 
to phone”  
60 
minutes 
If alert fires 
after 
10:59PM, 
refractory 
lasts until 
6:59AM. No 
refractory 
other hours 
of the day. 
After 1st re-
fire 
After 2nd re-
fire 
- 

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25 
phone_battery_low: 
Phone battery falls 
below 20% AND is not 
charging 
If phone is charging or 
level goes above 20% 
 
"Phone battery low. 
Please charge" 
10 
- 
After 1st re-
fire 
After 2nd re-
fire 
- 
26 
maximum_insulin_exc
eeded: Insulin Delivery 
≥ 35% TDIRadj on last 
hour 
Auto clears  
 
"Max insulin has been 
exceeded" 
- 
60 
Immediately 
Immediately 
- 
27 
cbg_equal_or_over_40
0: CBG ≥ 400 mg/dl 
AND alert 27 not active 
or refractory 
Ketone check 
 
"Blood glucose is 
above 400 mg/dl. 
Please change the 
insulin pod and check 
ketone levels now." 
15 
60 
Immediately 
Immediately 
- 
28 
ketone_level_high: 
Ketones ≥ 0.6 mmol/L 
User 
acknowledgement 
 
“Ketone levels are 
high. If not already 
done, please change 
the insulin pod. Do not 
exercise.” 
- 
- 
Immediately 
Immediately 
- 
29 
Insulin_pump_reservo
ir_low: Omnipod has 
less than 10% of fluid 
volume remaining. 
Pod with greater than 
10% volume is 
connected (i.e. pod is 
changed) 
 
Your insulin pod is 
low. Please deactivate 
your current pod and 
activate a new insulin 
pod. 
120 
- 
After 1st re-
fire 
After 2nd re-
fire 
- 
 
 
 
 
 
 
 
 
 
 
 

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Appendix E:  Exercise Video Outline 
 
 
Aerobic Exercise Video Outline 
Segment 
Segment Time 
Activities  
Warm-Up Intro 
(2 min) 
0:00 – 2:00 
0:00: Welcome! Marching Reach Up 
0:30: Side to Side Kick Back Pull Back 
0:45: Side to Side Kick Back Butt Kick 
1:00:  Side to Side Kick Back Butt Kick Reach out 
1:15: Grapevine 
1:30: Grapevine with Arm Circles 
Active Exercise 
(30 min) 
Each activity is performed 
for 30 seconds 
1. Modified Jump rope 
2. Jumping jacks 
3. Side to Side Knee Raise (alternate left/right 
crunch) 
4. Side Steps (active recovery) 
5. Modified Jump rope 
6. Jumping Jacks 
7. Side to Side Knee Raise (alternate left/right 
crunch) 
8. Side Steps (active recovery) 
9. Arms Alternating A, T and Y with Heal Tap 
10. Left Jab Bounce (left foot forward)  
11.  Side Steps (active recovery) 
12. Arms Alternating A, T and Y with Heal Tap  
13. Right Jab Bounce (right foot forward)  
14. Side Steps (active recovery) 
15. Right Leg Lunge Alternate Forward Back 

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16. Left Leg Lunge Alternate Forward Back 
17. Jog in Place Hands Raised 
18. Side Steps (active recovery) 
19. Right Leg Lunge Alternate Forward Back 
20. Left Leg Lunge Alternate Forward Back 
21. Jog in Place Hands Raised 
22. Side Steps (active recovery) 
23. Squat to Upper Cut (right foot forward) 
24. Right Jab Bounce (right foot forward)  
25. Side Steps (active recovery) 
26. Squat to Upper Cut (left foot forward) 
27. Left Jab Bounce (left foot forward)  
28. Side Steps (active recovery) 
29. Horse Stance Overhead Reach Side Bend/ 
Standing Alternating Side Bend  
30. Side Jump with Squat Alternating Left Right 
31. Right Lateral lunge with Right Knee Drive Pull 
Up 
32. Left Lateral Lunge with Left Knee Drive Pull Up 
33. Side steps (active recovery) 
34. Horse Stance Overhead Reach Side Bend/ 
Standing Alternating Side Bend  
35. Side Jump with Squat Alternating Left Right  
36. Right Lateral lunge with Right Knee Drive Pull 
Up 
37. Left Lateral Lunge with Left Knee Drive Pull Up 
38. Side steps (active recovery) 
 
 
 
 

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Appendix  F:  Instruction cards for participants to take additional carbs at the start of exercise as needed based on CGM and 
trend to avoid post-exercise lows 
 
Inpatient instruction card: 
 
 

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Outpatient instruction card:  
 

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References 
 
 
[1] 
J. R. Castle et al., "Randomized Outpatient Trial of Single- and Dual-Hormone Closed-
Loop Systems That Adapt to Exercise Using Wearable Sensors," Diabetes Care, vol. 41, 
no. 7, pp. 1471-1477, Jul 2018, doi: 10.2337/dc18-0228. 
[2] 
A. Weisman, J. W. Bai, M. Cardinez, C. K. Kramer, and B. A. Perkins, "Effect of 
artificial pancreas systems on glycaemic control in patients with type 1 diabetes: a 
systematic review and meta-analysis of outpatient randomised controlled trials," Lancet 
Diabetes Endocrinol, vol. 5, no. 7, pp. 501-512, Jul 2017, doi: 10.1016/S2213-
8587(17)30167-5. 
[3] 
P. G. Jacobs et al., "Randomized trial of a dual-hormone artificial pancreas with dosing 
adjustment during exercise compared with no adjustment and sensor-augmented pump 
therapy," Diabetes Obes Metab, vol. 18, no. 11, pp. 1110-1119, Nov 2016, doi: 
10.1111/dom.12707.