A Crossover Study to Assess the Effect of an Artificial Intelligence (AI)-Based Bedtime Smart Snack Intervention in Preventing Overnight Low Glucose in People With T1D on Multiple Daily Injections.
Phase: NA
Conditions: Type 1 Diabetes Mellitus With Hypoglycemia
Sponsor: Oregon Health and Science University

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PROTOCOL TITLE: A crossover study to assess the effect of an artificial intelligence (AI)-
based bedtime smart snack intervention in preventing overnight low glucose in people with 
T1D on multiple daily injections. 
PROTOCOL VERSION: 
DATE: 
9.0 
April 19, 2024 
STUDY SITE: 
Oregon Health & Science University 
3181 SW Sam Jackson Park Rd 
Portland, OR 97239 
FUNDING: 
National Institutes of Health / National Institute of 
Diabetes and Digestive and Kidney Diseases 
(NIH/NIDDK) 
PRINCIPAL 
INVESTIGATOR: 
Clara Mosquera-Lopez PhD 
CO-INVESTIGATORS: 
Clinical team: Leah M. Wilson MD / Diana Aby-Daniel 
PA-C 
Engineering team: Peter G. Jacobs PhD 
IRB: 
25174 
 
Background 
Despite the growing adoption of continuous glucose monitoring (CGM) and advances in insulin 
therapies, overnight low glucose is still a common problem for people living with type 1 diabetes 
(T1D). Nocturnal hypoglycemia, which accounts for 55% of level-two hypoglycemia events 
(glucose < 54 mg/dL) in people with type 1 diabetes (T1D) and 75% of level-two hypoglycemia 
events in children with T1D,[16]–[18] is particularly dangerous because people are unlikely to 
recognize symptoms while sleeping and are also less likely to awaken in response to 
hypoglycemia alarms from continuous glucose monitors (CGMs).[1], [2] In addition to the 
serious short-term effects of nocturnal hypoglycemia episodes, untreated nocturnal 
hypoglycemia can further impair the physiological counter-regulatory system and contribute to 
hypoglycemia unawareness.[3]–[5] Hypoglycemia unawareness may eventually result in 
recurrent asymptomatic hypoglycemia[19] and in some cases the dead in bed syndrome due to 
prolonged exposure to extremely low blood glucose levels during sleep.[20] 
Advanced insulin therapies such as continuous subcutaneous insulin infusion (CSII) with insulin 
pumps and closed-loop systems are now available for managing glucose. However, most people 
with type 1 diabetes continue to use multiple daily injections (MDI).[21], [22] A recent study 
showed that MDI users spent more time with sensor glucose <54 mg/dL and experience more 
hypoglycemia episodes overnight than pump or closed-loop users.[22] Therefore, there is a need 
for effective interventions that help people with T1D on MDI to prevent nocturnal 
hypoglycemia.  
Our group at the Oregon Health & Science University (OHSU) developed and evaluated a 
smartphone-based decision support app called DailyDose that combines CGM data and insulin 
data to provide comprehensive decision support for people with T1D on MDI. DailyDose 
provides on-demand insulin dosing recommendations, suggestions for glucose management 
around exercise, and hypoglycemia and hyperglycemia alarms.[6], [7] These features will not be 

2 
 
used in this study. A new feature of DailyDose, which will be evaluated in this study, is a 
module for prevention of low glucose overnight that provides a personalized bedtime smart 
snack recommendation based on the minimum overnight glucose level predicted by an advanced 
artificial intelligence (AI)-based model. 
 
Primary Objective 
To evaluate the benefit of an AI-based smart snack intervention (AI prediction model + 
personalized bedtime snack) in helping people avoid overnight low glucose as measured by the 
probability of overnight hypoglycemia, versus CGM-based glucose management (control 
period). 
 
Secondary Objectives 
• To measure time from bedtime until first CGM measurement <70 mg/dL if CGM stays 
below 70 mg/dL for at least 10 minutes  
• To evaluate the effect of an AI-based smart snack intervention versus CGM-based 
glucose management (during control period) on glucose control overnight (announced 
bedtime + 8 hours) and across the full 24-hour/day study duration, as measured by other 
glycemic outcomes including the following metrics: 
o % time < 54 mg/dL 
o % time < 70 mg/dL 
o % time 70-180 mg/dL 
o % time > 180 mg/dL 
o % time >250 mg/dL 
o Mean CGM 
o Number of bedtime snacks treatments 
• To assess the accuracy of the AI model in predicting overnight low glucose as measured 
by sensitivity and specificity during the control arm of the study. 
 
Study hypothesis 
We hypothesize that a smartphone-based bedtime smart snack intervention informed by a low 
glucose prediction AI model will reduce the probability of overnight hypoglycemia by 50% in 
people with T1D on MDI therapy compared with traditional CGM-augmented MDI glucose 
management. The probability of overnight hypoglycemia will be measured as the proportion of 
nights with nocturnal hypoglycemia episodes during intervention and control periods. 
Endpoints 
Primary endpoint 
Probability of overnight hypoglycemia. An episode of overnight hypoglycemia is counted if 
sensor glucose is <70 mg/dL for at least two measurements during an eight-hour period 
following announced bedtime. 
Time frame: The level-one unit of analysis is a single night, and each participant will contribute 
27 consecutive nights under each condition. 
Secondary Endpoints 

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• Time to the first low-glucose event (<70 mg/dL). Time until first CGM measurement <70 
mg/dL when CGM remains < 70 mg/dL for at least 10 minutes 
• Percentage of time in clinically relevant glucose ranges: 
o % time < 54 mg/dL 
o % time < 70 mg/dL 
o % time 70-180 mg/dL 
o % time > 180 mg/dL 
o % time >250 mg/dL 
Time frames: overnight (announced bedtime + eight hours) and across the full 24-
hour/day study duration 
• Mean glucose in mg/dL 
Time frames: overnight (announced bedtime + eight hours) and across the full 24-
hour/day study duration 
• Accuracy of overnight low glucose prediction as measure by sensitivity and specificity as 
measured during the control arm of the study 
• Change in weight from start to end of intervention period, start to end of control period 
 
Study Type 
This is a single-center, open-label, crossover trial with two arms and two periods (2x2) and one-
week washout period. The study is designed to evaluate the efficacy of an AI-based bedtime 
smart snack intervention in reducing nocturnal low glucose in people living with T1D on MDI 
therapy compared with traditional CGM-augmented MDI therapy as the control.  
 
Study population 
The study population will be adults with type 1 diabetes, aged 18 or older. Younger participants 
are excluded as it is appropriate to assess efficacy of proposed intervention first in the adult 
population. Twenty participants will be recruited to participate in this study. 
 
Power analysis 
A sample of 20 participants observed for 27 nights in each condition (total number of nights = 
20*27*2 = 1,080) provides >90% power to detect a relative risk (RR) of 0.5 for nights in the 
intervention period compared to the control period, or >80% power to detect RR≤0.6. This was 
calculated assuming the risk of 0.09 for overnight hypoglycemia in the intervention period vs 
0.18 in the control period (or 0.15 for RR=0.6), and an intra-cluster correlation coefficient (ICC) 
of 0.25. The effect is equivalent to a 50% relative reduction in the likelihood of nocturnal 
hypoglycemia. 
Statistical power for this sample size was calculated by simulating 1,000 datasets with the 
assumptions above, fitting the mixed effects model, and determining the proportion of those 
datasets where the p value for the Wald test of the coefficient of the treatment effect was <0.05. 
Control and intervention proportions were set after reviewing other crossover trials of similar 
interventions in similar populations.[22], [23] The ICC was determined by drawing samples of 

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20 individuals/27 nights per person per arm from a combined dataset of nights from the T1D 
Exercise study T1-Dexi dataset (T1-Dexi is the largest known dataset of physical activity in 
T1D, a joint effort by The Leona M. and Harry B. Helmsley Charitable Trust, Jaeb Center for 
Health Research, and the T1-Dexi study group) and a dataset provided to our group at OHSU by 
Glooko Inc (Mountain View, CA, USA), then calculating the ICC in an unconditional model. An 
ICC of 0.25 is just below the mean for ICCs calculated over 500 resamples (ICCMEAN = 0.27). In 
the resampled source data, 85% of participants experienced hypoglycemia on at least one of the 
27 sampled nights. 
 
Protocol summary 
Participants will be randomized to either first use CGM only to manage glucose for four weeks 
(control arm, usual care) followed by four weeks of DailyDose App + bedtime smart snack 
intervention (intervention arm), or vice-versa. There will be a one- to four week washout period 
between arms. See Figure 1 for a diagram of the study flow. 
During the control arm, participants will wear CGM and will manage their glucose as usual 
(current care). Participants will be asked to wear a smart watch overnight to collect sleep metrics, 
weigh themselves weekly in the morning before eating, and answer a one-item sleep quality 
scale survey weekly. We will collect CGM measurements during the control arm for evaluation 
of effect of intervention and assessment of the accuracy of low glucose prediction. 
During the smart snack intervention arm, participants will use the DailyDose app when they are 
getting ready for bed. An AI-based model in DailyDose will predict the likelihood of overnight 
low glucose at bedtime every night and will recommend a personalized snack to help avoid 
nocturnal hypoglycemia. The nutritional content of the snack (carbohydrate, protein, fat, etc.) 
will be dependent on the predicted overnight minimum glucose and the predicted time of the 
minimum overnight glucose level. During this arm, participants will also be asked to wear a 
smart watch overnight, weigh themselves weekly, and answer a one-item sleep quality scale 
survey weekly. 
 
 

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Figure 1. Study flow diagram 
 
Subject criteria 
Inclusion criteria 
• Diagnosis of type 1 diabetes mellitus for at least 1 year 
• Male or female participants 18 years of age or older 
• Using multiple daily injections 
• HbA1c <10% at screening 
• Current use of a continuous glucose monitoring system with at least two episodes of 
overnight hypoglycemia (defined as sensed glucose <70 mg/dL for at least 10 minutes 
between the hours of 10 PM and 6 AM) within 30 days prior to screening 
• Individuals with history of severe hypoglycemia requiring third party assistance must 
have a companion in the same dwelling as the study participant who will be linked to the 
participant’s Dexcom app during the control arm of the study, and who is trained in the 
administration of glucagon. 
• Willingness to follow all study procedures 
• Willingness to sign informed consent and HIPAA documents 
Exclusion criteria 
• Individual 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 
• Any active infection 
• Known or suspected abuse of alcohol, narcotics, or illicit drugs (except marijuana use) 
• Seizure disorder 
• Use of non-insulin glucose lowering medications 
• Use of steroids 
• Stage-three or more advanced chronic kidney disease 
• Cirrhosis 
• Hypo- or hyper- thyroidism that is not medically optimized and on a stable regimen 
define as Thyroid-stimulating hormone (TSH) outside of the normal reference range 
based on screening labs 
• Adrenal insufficiency 
• 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). 
• Any clinically significant disease or disorder which in the opinion of the Investigator may 
jeopardize the participant’s safety or compliance with the protocol 
• Individual working night shifts 

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Subject 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 Subject 
Recruitment website. Handouts may also be made available to faculty at Tuality, Providence, 
Kaiser Permanent, 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 (OHSU diabetes 
research registry and/or www.clinicaltrials.gov). Participants will be contacted using the 
approved telephone screening script and email template. 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. 
 
This study will use Epic MyChart® to recruit potential participants. Researchers will send MRNs 
of potential participants that look eligible for the study to the EPIC research team. EPIC research 
will load the potential participants into the research recruitment in-basket. Researchers will then 
run the program and all MyChart® recruitment messages will send to potential participants 
asking them to participate. There is no risk of duplicate invitations as it is based on MyChart® 
accounts combined with Epic records and no duplication is possible.  
 
Up to 40 participants may be screened in this study. Goal enrollment is 20 participants. Up to 3 
participants will be replaced if needed, with a total enrollment of up to 23 participants. 
 
Withdrawal Criteria 
A participant may withdraw at will at any time or at the discretion of the investigator. A 
participant must be withdrawn if the following applies: 
• Protocol deviation having influence on efficacy or safety as judged by the Investigator 
• Substantial and repeated non-compliance with trial procedures 
• Pregnancy 
• Intention of becoming pregnant 
 
Study procedures 
Screening session 
Screening will take place within 12 weeks prior to the start of the first arm of the study. 
Screening visits will take place at OHSU’s Biomedical Engineering Point of Care (BME POC) 
Laboratory, the Harold Schnitzer Diabetes Health Center, or virtually using WebEx. This visit 
will take approximately 1.5 hours. 
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 questions they might have. Prior to any 
screening procedures, study staff will explain the study, give the participant ample time to ask 

7 
 
questions and consider participation, and ensure that the participant voices their 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. For virtual screening visits, participants will be consented 
over WebEx and study staff will witness them signing consent. Participants will sign two consent 
forms. After the participant has signed the consent, a copy of the consent/authorization form will 
be given or sent to OHSU staff by the participant. For virtual visits, participants will keep one 
copy of the signed consent form and ship one to OHSU overnight. The original will be kept for 
the source document. 
Study personnel will review medical history and medications.  A physical exam performed 
within the last year will be reviewed by investigator via chart review. Height and weight 
measures will be obtained both in clinic and using a home scale for in-person visits. For virtual 
visits, height and weight will be self-reported to staff; weight will be measured using a home 
scale or taken from clinic note within the past year. Blood pressure and heart rate will be 
obtained from chart review by study staff or from at-home monitoring unit (if participant is in 
possession of one). 
Individuals of child-bearing potential will take a urine pregnancy test (UPT), 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) and thyroid-stimulating hormone (TSH). Blood draw labs and urine pregnancy 
testing will be completed within 1 week of screening at an OHSU outpatient phlebotomy lab. If a 
participant had any of these labs drawn with in the last 6 months and results are available for 
review within Epic or CareEverywhere for the study investigator to review, then those labs do 
not need to be drawn at this point. 
A study investigator will assess inclusion/exclusion criteria and may review the participant’s 
medical record for clarification as needed. The participant’s glucose sensor data will be 
downloaded at the time of the screening visit or accessed online to confirm that the participant 
has experienced nocturnal hypoglycemia (i.e., two events) in the 30 days prior to the screening 
visit. A three-digit participant ID number will be assigned to the participant. Participants will 
complete hypoglycemia awareness, diabetes distress scale, hypoglcemia fear survey, and sleep 
quality questionnaires that will serve as a baseline to compare against results obtained at the end 
of the intervention period. 
Randomization 
Participants will be randomized to start with the control or smart snack condition in 1:1 ratio 
using blocks of size 4 to 6 to ensure balance over the entire sample. Blinding of participants and 
study staff is not feasible; some analyses may be conducted under blinding.  
Participants will be given a study Apple iPhone, and if not already using for personal use, a 
Dexcom G6 transmitter and sensor to use during the study, as well as an Apple Watch that will 
be paired with the study iPhone, and a study scale. All study devices, including a urine 
pregnancy test if applicable will be given to the participant during this visit or delivered via 
courier. 
Control arm (4 weeks) 
There will be a visit at the start of the control arm that will be held virtually using WebEx. This 
visit can be held in clinic. The purpose of this visit is to have the participants learn how to use 
study devices and the Dexcom app. Using the Webex platform, study staff can connect virtually 

8 
 
with participants for training on the devices and study procedures while they are at home. 
Participants will be trained in how to use the Dexcom G6 CGM system for those not already 
using the Dexcom G6 system including insertion, sensor change, and calibration. For participants 
who are current users of Dexcom G6 CGM system, the insertion, change, and calibration of the 
Dexcom G6 CGM device will not be discussed during this meeting. Participants will be trained 
in how to pair the Dexcom G6 transmitter to the Dexcom app on a provided study smart phone, 
to start and stop a new sensor session, and how to enter calibrations. The CGM alerts will be set 
at 70 mg/dL and 250 mg/dL. For participants with history of severe hypoglycemia requiring third 
party assistance, low glucose alerts will be conservatively set to 85 mg/dL. Participants can 
modify these settings. Participants will be instructed to manage their glucose as they normally 
do. For those participants with history of severe hypoglycemia requiring third party assistance, a 
participant’s companion (who lives in the same house and is trained in the administration of 
glucagon as per study inclusion criteria) will be linked to the participant’s Dexcom app. The 
Apple Watch will be paired with the Apple iPhone by the study staff before giving them to 
participants. Participants will be trained in how to use the Apple Watch, which will be used 
during the study to collect sleep data. This visit will take approximately 0.5 - 1.5 hours, 
depending on the subject’s experience. 
At the beginning of the control period, participants will record their weight using a scale 
provided by the study staff.  During the 4-week control period, participants will wear Dexcom 
G6 CGM and the study Apple Watch. The Apple Watch will be used to track sleep metrics; 
therefore, participants are asked to wear the smart watch overnight and charge it during the day. 
The goal of this control period is to gather CGM glucose data to assess baseline time in 
overnight hypoglycemia (<70 mg/dL and <54 mg/dL) and other glucose control metrics (mean 
glucose, % time in range 70-180 mg/dL, % time below range, % time above range) and evaluate 
the accuracy of the overnight low glucose prediction algorithm.  
Participants will weigh themselves weekly in the morning after urinating and before eating their 
first meal and to record their weight to track baseline weight changes. Participants will also 
answer a one-item sleep quality survey weekly.  Participants will be contacted weekly by study 
staff to collect weight measurements and responses to the sleep quality question.  
There will be a closeout visit at the end of this arm that will last 10-15 minutes. This visit can be 
held virtually. Availability of Dexcom CGM data will be confirmed by the study staff and the 
participant will be asked about adverse events and medication changes. Participants that will use 
their own Dexcom G6 will share their Dexcom Clarity data with the clinic at this visit.   
 
DailyDose + smart snack intervention arm (4 weeks) 
There will be a visit at the start of the intervention arm that will be held at OHSU’s Biomedical 
Engineering Artificial Intelligence for Medical Systems (AIMS) Laboratory, the Harold 
Schnitzer Diabetes Health Center, or virtually using WebEx. A urine pregnancy test might be 
required for individuals of childbearing potential if the last pregnancy test was more than 7 days 
prior. This test must be negative before further participation is allowed. During this session, 
participants will go through the onboarding process with the DailyDose app. This process will 
occur with the study staff and involve: 
• Training on using the Dexcom G6 CGM within the DailyDose app 
• Setting up low and high blood glucose CGM-based alerts 

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• Setting up bedtime for running nocturnal low glucose prediction and receiving bedtime 
snack recommendation when applicable 
• Review smart snack options that will be recommended by DailyDose and provided to 
participants during the intervention period (study protocol, Table 1) as well as present 
accessible snack alternatives (e.g., those already documented in the study protocol Table 
2), in case participants has any allergies or food aversion related to DailyDose smart 
snack options. The study staff will also provide a card with bedtime snack options and 
replacements so that participants can easily find adequate alternatives to the snacks 
recommended by DailyDose (study protocol, Appendix F). 
• Training on usage of the DailyDose app including how to setup alerts, predict likelihood 
of nocturnal low glucose, accept/decline smart snack recommendations, and use of the 
insights tab / settings / logbook features 
• Training on usage of the Apple Watch 
DailyDose has glucose alerts for safety. The Dexcom G6 CGM alerts in DailyDose will be set at 
70 mg/dL and 250 mg/dL with user able to adjust. For participants with history of severe 
hypoglycemia requiring third party assistance, low glucose alerts will be conservatively set to 85 
mg/dL.  There is a very low glucose alert (glucose <55 mg/dL) that cannot be adjusted.  
This visit will take approximately 2-3 hours, depending on the subject’s experience. 
Participants will go home and use the nocturnal low glucose alert feature of the DailyDose 
system for the next four weeks. Study staff may contact participants via text message or phone 
call at other times at the investigator’s discretion. At the beginning of the intervention period, 
participants will record their weight using the scale provided by the study staff. Participants will 
wear Dexcom G6 CGM and the study Apple Watch. The Apple Watch will be used to track sleep 
metrics. Participants will use DailyDose and an AI-based prediction model to predict at bedtime 
the likelihood and time of the minimum overnight glucose. A smart snack recommendation will 
be given if there is a probability of overnight glucose drop below 70 mg/dL. The recommended 
bedtime treatment will have a carbohydrate content between 15 or 30 g depending on the 
predicted glucose drop, and a glycemic index defined by the estimated time of the predicted 
hypoglycemia event. If nocturnal hypoglycemia (glucose < 70 mg/dL) is predicted to occur 4 
hours after bedtime, the recommended snack will have a balance of carbohydrate with higher 
amounts of protein or fat content. Several snack options will be provided to participants, so that 
there is more uniformity across participants (see Table 1). Participants will be instructed to 
manage their glucose as they normally do with the addition of these smart snack 
recommendations. Participants will have the ability to accept or decline smart snack 
recommendations. 
Table 2 shows nutritional content of the options for recommended snacks. 
 
Smart snack 
options 
Low glucose predicted 0-4 
hours after bedtime 
Low glucose predicted 4-8 hours after 
bedtime 

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Small 
 
 
 
 
Large 
 x 2 
x 2 
x 2 
 
Table 1. Smart snack options and recommended amounts based on overnight low glucose 
predictions. The CLIF BUILDERS protein bars are gluten free. The Oats ‘n Honey bars might 
contain trace amounts of gluten. 
Snack option  Quantity  Measure  Wgt 
(g)  
Cals 
(kcal)  
Prot 
(g)  
Carb 
(g)  
Fat 
(g)  
TotFib 
(g)  
Sugar 
(g)  
SLOW ABSORPTION   
Granola bar, 
crunchy, oats and 
honey  
1  
Each  
21  
95  
1.5  
14.5  
3.5  1  
5.5  
Protein bar, 
chocolate peanut 
butter, Builders  
1  
Each  
68  
290  
20  
29  
11  
--  
17  
Protein bar, 
chewy, peanut 
almond & dark 
chocolate  
1  
Each  
40  
200  
10  
15  
12  
--  
6  
Protein bar, 
chocolate, 
Builders  
1  
Each  
68  
280  
20  
31  
9  
--  
17  

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Protein bar, 
vanilla almond, 
Builders  
1  
Each  
68  
290  
20  
29  
11  
--  
16  
QUICK ABSORPTION  
Juice drink, 
cranberry 
cocktail  
4  
Ounce-
weight  
113.4  53.83  
0  
13.46  0  
0  
13.46  
Juice, orange  
4  
Ounce-
weight  
113.4  54.65  
0  
12.75  0  
0  
11.29  
Table 2. Smart snack options with macro nutrient analysis.  
 
Participants will weigh themselves weekly in the morning after urinating and before eating their 
first meal and to record their weight to track baseline weight changes. Participants will also 
answer a one-item sleep quality survey weekly. Participants will be contacted weekly by study 
staff to collect weight measurements and responses to the sleep quality question.  
At the end of the intervention period, participants will complete hypoglycemia awareness, 
diabetes distress scale, hypoglycemia fear survey, and sleep quality questionnaires to compare 
results with the questionnaires completed during the screening session. 
There will be a closeout visit at the end of this arm that will last about 30 minutes. This visit can 
be held virtually.  Availability of Dexcom CGM data will be confirmed by the study staff and the 
participant will be asked about adverse events and medication changes.   
Washout period (1 - 4 weeks) 
There will be a one- to four week washout period between the control and intervention arms (or 
between intervention and control arms depending on randomization sequence). The use of the 
DailyDose app will be discontinued during this period for those participants who were 
randomized to start using DailyDose. Participants will use their own sensors during the washout 
period and will manage their glucose as they normally do. Participants are not required to weigh 
themselves, complete questionnaires, or wear the Apple Watch during this week. No visits are 
scheduled during the washout period.  
 
Study Completion session 
This visit will be completed within 2 weeks of completion of all study procedures. Participants 
will participate in a 1:1 online meeting with study staff. In this session, study staff will share 
with participants the factors that contributed to higher predicted probability of nocturnal low 
glucose during the study (e.g., if a certain type of exercise was to be the biggest contributor to 
nocturnal hypoglycemia risk). Participants will complete a short survey to evaluate usability 
aspects of the DailyDose overnight low glucose prevention module using a structured script. This 
meeting will take about 1 hour and will be recorded after receiving participant’s authorization. 
Participants can also receive information about their risk factors for overnight low glucose and 
complete the closing survey over the phone in a call with study staff. 
Participants will be given shipping boxes for sending all study devices back including the Apple 
iPhone, Apple Watch, Dexcom G6 transmitter and scale, as well as paper forms with weight 
records and survey responses. After this session all study devices will be turned in. If the 4-week 
DailyDose + smart snack intervention period or the control period are paused for a period of time 

12 
 
due to technical problems, the participant may be asked if they can complete additional time in 
study with the goal to collect at least 2 weeks worth of data in at least one of the arms of the 
study, such that the participant can be included in the statistical analysis. Additional 
compensation will be provided for additional time in study. Problems that would qualify for 
extending the study time are 1) insufficient study supplies requiring the participant to go off of 
DailyDose + smart snack intervention or to discontinue the control arm for a period of time (such 
as running out of CGM supplies or bedtime snacks), 2) issues with the smartphone such that 
DailyDose cannot be used/accessed (such as a due to a damaged phone or problems with the 
internet connection that prevent data from being uploaded to the remote monitoring system), 3) 
issues with the CGM system or the capture of the CGM data during the control period or during 
the intervention period such that DailyDose cannot generate bedtime recommendations due to 
insufficient CGM data, or 4) scheduling issues such that the participant is unable to complete the 
control or the DailyDose + smart snack intervention period continuosly. Participants can 
complete up to 4 additional weeks to make up time the study was paused for technical reasons. 
Repeating the study time will be optional.The study team will track when participants extend 
their study time and the reason and this will be included in the annual report to the FDA.

13 | P a g e  
 
 
 
Table 3: Schedule of Events 
1 DailyDose abbreviated Dd 
2 Randomization order abbreviations Control first (CG) Intervention first (IG) 
3 (CG) only 
4 (IG) only 
  
Screening  
1st 4 weeks 
2nd 4 weeks 
 
 
 
 
Study 
Completion 
Visit  
Description of visit 
procedures  
Dd1 
(IG)2 or 
Control 
(CG)2 
initiation 
visit 
Phone 
check-
in 
Phone 
check-
in 
Phone 
check-
in 
Dd1 
(IG)2 
or 
Control 
(CG)2 
close 
out 
visit 
Dd1 
(CG)2 or 
Control 
(IG)2 
initiation 
visit 
Phone 
check-
in 
Phone 
check-
in 
Phone 
check-
in 
Dd1 
(CG)2 or 
Control 
(IG)2 
close out 
visit 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Visit Window 
  
1-84 
days 
7 days  7 days  7 days  7 days  
7 days  
7 days  7 days  7 days  7 days  
14 days 
Visit Activities and 
Data Collection 
  
  
  
  
  
  
  
  
  
  
  
 
Consent participant, 
signing consent form 
and HIPAA 
X 
  
  
  
  
  
  
  
  
  
  
 
Assess subject 
eligibility to participate 
in study 
X 
  
  
  
  
  
  
  
  
  
  
 
Measure height 
X 
  
  
  
  
  
  
  
  
  
  
 
Measure weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Measure BP and pulse 
X 
  
  
  
  
  
  
  
  
  
  
 
Physical exam 
performed by 
investigator 
X 
  
  
  
  
  
  
  
  
  
  
 

14 | P a g e  
 
 
 
Collect demographic 
and other baseline 
characteristics  
X 
  
  
  
  
  
  
  
  
  
  
 
UPT if applicable and 
not done in last 7 days 
(Point of care) 
X 
X 
  
  
  
  
X 
  
  
  
  
 
Collect blood sample 
for HbA1c, CBC, 
CMP, TSH testing 
X 
  
  
  
  
  
  
  
  
  
  
 
Collect information 
about medical history 
X 
  
  
  
  
  
  
  
  
  
  
 
Collect information 
about concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Download participant's 
glucose sensor 
X 
  
  
  
  
  
  
  
  
  
  
 
Complete 3 surveys 
X 
  
  
  
  
X4 
  
  
  
  
X3 
 
Randomization 
  
X 
  
  
  
  
  
  
  
  
  
 
Collect data on 
Adverse Events 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Train participants on 
the study procedures to 
do at home 
  
X 
  
  
  
  
X 
  
  
  
  
 
Train participants on 
use of Dexcom G6 
CGM system with G6 
and Clarity apps 
  
X3 
  
  
  
  
X4 
  
  
  
  
 
Train participants on 
use of Apple Watch 
  
X 
  
  
  
  
  
  
  
  
  
 
Collect sleep quality 
survey response 
  
  
X 
X 
X 
X 
  
X 
X 
X 
X 
 

15 | P a g e  
 
 
 
Training on using 
DailyDose including 
setting up Dexcom G6 
with alerts and snack 
recommendations 
  
X4 
  
  
  
  
X3 
  
  
  
  
 
Schedule upcoming 
visits 
  
X 
  
  
  
  
X 
  
  
  
  
 
Confirm availability of 
Dexcom G6 CGM data 
in Clarity 
  
  
  
  
  
X3 
  
  
  
  
X4 
 
Complete usability 
survey 
  
  
  
  
  
  
  
  
  
  
  
X 
Collect study devices 
  
  
  
  
  
  
  
  
  
  
  
X 

16 | P a g e  
 
 
 
Stopping rule criteria 
The study will be stopped if any of the following occur after the start of the study: 
• The participant requests that the treatment be stopped 
• Participant pregnancy 
• One episode of diabetic ketoacidosis as defined 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. 
• One episode of severe hypoglycemia defined as a hypoglycemic event resulting in altered 
consciousness requiring another person to actively administer carbohydrate, glucagon, or 
other resuscitative actions.   
 
Cleaning and Disinfecting 
All devices will be cleaned and disinfected between participants. The Apple iPhone andApple 
Watchwill be 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 Germicidal 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 
subject information.  
 
Data Collection 
We will be collecting de-identified physiologic data from people with T1D.  The following data 
will be collected from participants in this study: 
• Glucose sensor data (Dexcom G6 system) 
• Self-report bedtime snack and exercise data logged by the participant on DailyDose 
• Self-report weight logged by participant 
• Sleep data from Apple Watch 
• Responses to surveys 
To collect the data, each participant in the study will be given an Apple iPhone and an Apple 
Watch.  The iPhone will have the Dexcom G6 app and the DailyDose app installed. These apps 
will collect CGM data and log related to physical activity, bedtime snacks, and overnight low 
glucose predictions. The data from the Apple Watch will be exported from Apple Health or 
Apple iTunes as .cda or .xml files. 
The DailyDose app will serve as the “data aggregator” on the phone and will perform the 
following functions: 
• Collect self-report bedtime snacks and exercise data from the participants 
• Aggregate all the data collected from the glucose sensor and self-logged snacks and 
exercise data 
•  to be stored as de-identified data within the iCloud storage area of the phone 
 

17 | P a g e  
 
 
 
DailyDose Guidance Remote Monitoring (GRM) Cloud Server 
All the data collected will be streamed over the Internet (using secure sockets encryption) to an 
OHSU secure instance of an AWS cloud storage server every five minutes. Authentication 
between the phone and the AWS server is done using self-expiring JSON Web Tokens (JWT). 
Data transmitted between the phone and the AWS server is encrypted using HTTPS/SSL. The 
code managing authentication and data transfer is Python version 3.7.0. Data acquired from the 
app is displayed via a physician web portal. The physician web portal user interface is written in 
Javascript version 1.8.5. There is no personally identifiable data stored with the data sent to the 
AWS server. The server shall be capable of receiving the following types of data from 
DailyDose (1) overnight low glucose predictions and smart snack recommendation data, (2) 
CGM data, (3) alerts, (4) settings.  All types of data shall be indexed by subject ID and by 
date/time. Each data packet shall be accompanied by an authenticated JWT token. The AWS 
server has undergone a security review by OHSU IPS. 
 
Confidentiality and Protection of Human Subjects 
Access to data/specimens is restricted to study personnel. Access to data requires OHSU 
ID/password authentication. 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. The data stored within the GRM Cloud Server and Dexcom Clarity is 
de-identified and does not contain any information from the 18 HIPAA designations of 
personally identifiable information.  OHSU ITG has granted an Exception approval for using and 
storing data on the GRM. Data stored on the GRM will be deleted once the study is complete. 
 
We will install the OHSU Intelligent Hub on the iPhones.  Upon enrollment, participants will be 
assigned with a three-digit code to protect their privacy. The three-digit code will be used instead 
of their name, medical record number, or other personally identifying information. The key 
associating the code and the participants personal identifying information will be restricted to the 
PI and study staff. The key will be encrypted and kept secure on a restricted OHSU network 
drive in a limited access folder as stated below. The iPhones will be registered to the study 
participants’ unique study ID number and all the data stored on the iPhone will be associated 
with this ID. 
The three-digit identifying subject number will also be used to code paper study documents. 
Study staff will record data required by the protocol onto the Case Report Forms (CRF) during 
the study. The CRFs and all surveys will be collected on paper. Data for this project will be 
stored on the GRM, developed and maintained by our group, that has undergone a security 
review. Investigators and research coordinators will verify that the procedures are conducted 
according to the approved protocol. All paper source documents will be kept in a locked cabinet 
for a minimum of five years. The CRFs will include: 
• Screening form 
• Control arm start-up visit 
• Control arm completion visit 
• Intervention arm start-up visit 
• Intervention arm completion visit 
• Surveys 

18 | P a g e  
 
 
 
• Study completion visit 
• Physician CGM Review Form 
• Phone/Email Update Form 
• Adverse Event form 
• Serious Adverse Event form 
• Concomitant Medications 
The Principal Investigators may authorize other personnel to make entries in the CRF. The coded 
data will be stored in the OregonAPC repository according to IRB protocol 19858. 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. During 
screening, all participants will sign the consent form to store their study data in the data 
repository. 
To protect confidentiality, standard institutional practices will be followed to maintain the 
confidentiality and security of data collected in this study. Study staff will be trained with regard 
to these policies. 
Paper files will be stored in locked filing cabinets in restricted access offices at site. 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. Electronic data will be stored 
on encrypted computers, laptops, and study smartphones. Electronic data is stored in OneDrive. 
DailyDose data will be housed in a custom cloud database on an OHSU secure server called the 
GRM. Access to data/specimens is restricted to study personnel. Access to data requires 
ID/password authentication. 
 
Risk and Benefits 
Risks: The risks of the protocol procedures are considered minor. Daily management of glucose 
for people with type 1 diabetes brings a risk of hyperglycemia and hypoglycemia, but users are 
unlikely to experience severe low or high blood sugar because there are low and high glucose 
alerts available with the DailyDose app. Other risks are those associated with CGM use, but not 
directly related to this study. The following events have been identified as possible anticipated 
device-related adverse events of the FDA-approved 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 adverse events) 
• Edema from sensor and/or adhesive tape that is significant and non-resolving within 48 
hours of sensor pod removal 

19 | P a g e  
 
 
 
• Erythema from sensor and/or adhesive tape that is significant and non-resolving within 
48 hours of sensor pod removal 
• 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. 
There is a risk that the participant may consume a smart snack at night in response to the 
nocturnal low glucose alert and become hyperglycemic overnight.  The DailyDose app will alert 
the participant if their glucose becomes too high using the high glucose alerts within the app. 
Participants will be instructed to manage high glucose levels as they usually do. 
Benefits: The subject may not directly benefit from being in this study; however, their 
participation may help to advance decision support tools for preventing dangerously low glucose 
levels overnight. 
 
Costs 
Participants will receive $400 for completion of the study. If participants withdraw early from 
the study, compensation will be given as follows: $40 per week for the control or DailyDose + 
smart snack periods. There is no compensation for the screening visit. If a participant completes 
additional time on study to make up for time the study was paused due to technical issues, 
participants will receive an additional $40 per week. 
 
Monitoring Procedures 
This investigation will be monitored by Leah M. Wilson, MD and Joseph El Youssef, MD. Dr. 
Wilson and Dr. El Youssef have no commercial interest in any of the companies which 
manufacture any of the devices used in this study. 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 greater 
protection to the individual subject. 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. 
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 

20 | P a g e  
 
 
 
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. 
Triggers for reporting unanticipated problems are seizure, hospitalization, death, or any other 
occurrence considered serious by the PI. If ongoing monitoring of the studies reveals studies 
repeatedly being terminated because of unresponsive hyperglycemia or repeated serious 
hypoglycemia (resulting in altered mental status, loss of consciousness, or seizure), then the 
study will be discontinued immediately. If studies in two participants are stopped for severe 
hypoglycemia or severe hyperglycemia, then the entire study will be halted. Severe 
hypoglycemia is defined as an event requiring the assistance of another person to administer 
carbohydrate, glucagon, or resuscitative actions. Severe hyperglycemia is defined as capillary 
blood glucose that exceeds 300 mg/dl with serum ketones 3.0 mM or higher. 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. 
At all study visits, study staff will determine if any device, disease, or study-related adverse 
events (AEs) have occurred. Any adverse event (AE) and/or unanticipated problem (UP) will be 
reported to the investigator monitor immediately by one of the investigators. All study, disease or 
device-related AEs or UPs will be monitored until adequately resolved or stable. 
Information regarding all 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 
 
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 Investigator 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 FDA within ten (10) working 
days of the original SAE notification. 
If determined that the UADE presents an unreasonable risk to participants, the investigators will 
terminate all investigations or parts of investigations presenting that risk as soon as possible, but 
not later than five working days after such determination is made and not later than 15 working 
days after first notice of the original SAE. A terminated study will not be resumed without IRB 
and FDA approval. 

21 | P a g e  
 
 
 
 
Medical Device Reporting (MDR) Events 
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. For purposes of this protocol, the CGM device is currently marketed. Therefore, 
the investigator will follow the required reporting regulations if an MDR reportable event occurs, 
according to standard operating procedures and FDA guidelines. (US MDR Reporting; Code of 
Federal Regulations Title 21 Part 803). 
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). 
 
Adverse event reporting 
Hypo- and hyperglycemia will not be considered AEs unless the subject has positive ketones of 
1.2 mM or displays symptoms of hypoglycemia such as: loss of consciousness, slurred speech, 
hospitalization, or EMS services called. 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 AEs in this study. 
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 participants 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 UPs and adverse events, including those that do not meet the requirement for 
RNI, will be submitted with the continuing review. The FDA will be notified of any 
unanticipated adverse event related to the use of the study device. Notification will be made 
within 10 days after the Principal Investigator becomes aware of the event. Any SAE, including 
death, due to any cause (related or unrelated to devices), that may occur during a clinical study 
will be reported immediately (within 1 working day of learning of the event). 
 
Statistical analysis methods 
The differences between the control and intervention arms will be evaluated using a multilevel 
mixed effects model with nights (or 24-hour/day study duration) as the level 1 units of analysis 
and study participants as level 2. The outcome 𝑌𝑌𝑖𝑖𝑖𝑖 for the ith night for the jth participant is given 
by the following equation: 
𝑌𝑌𝑖𝑖𝑖𝑖= 𝛽𝛽0 + 𝛽𝛽1𝑇𝑇𝑇𝑇𝑖𝑖𝑖𝑖+ 𝛽𝛽2𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑗𝑗+ 𝛽𝛽3𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑖𝑖𝑖𝑖+ 𝑏𝑏0𝑗𝑗+ 𝜖𝜖𝑖𝑖𝑖𝑖 
- 
𝑇𝑇𝑇𝑇𝑖𝑖𝑖𝑖= 0 for the control condition or 𝑇𝑇𝑇𝑇𝑖𝑖𝑖𝑖= 1 for the smart snack intervention,  
- 
Sequence = AB or BA at the participant level, and  
- 
Period =1 or 2 

22 | P a g e  
 
 
 
- 
The term 𝑏𝑏0𝑗𝑗 represents a random intercept for participant to reflect the correlation 
between repeated measurements; a random slope for the treatment effect may also be 
considered.  
A significant Wald test for the coefficient of the treatment variable, β1, would provide evidence 
that the intervention differed significantly from the control condition.  
A significant Wald test for the coefficient of the sequence variable, β2, would indicate that there 
was a carryover effect. 
A p value less than 0.05 will be considered statistically significant. 
Covariate adjustment: Sequence and period will be included in statistical models as described 
above but are not expected to be statistically significant. 
Compliance analysis: We will model the overnight hypoglycemia endpoint with 
recommendation accepted/rejected as a predictor in the intervention period to test if accepting 
recommendations is associated with lower risk of nocturnal hypoglycemia. 
Adjustment for multiplicity: No adjustments will be made for multiplicity for the pre-specified 
primary and secondary outcomes. 
Hypothesis testing framework: All comparisons will be made as tests of equivalence. 
Interim analyses:  Interim analysis might be performed to define if more participants are 
included in the study if a participant does not experience any overnight hypoglycemia episode 
during the control arm. 
Timing of final analysis: Final analysis will be completed after data collection and processing is 
complete. 
Missing data 
Participants who contribute at least 14 nights plus 24 hours following bedtime in at least one of 
the study conditions will be included in the analysis. Missing sensed glucose values will be 
interpolated for up to 30 min segments. Longer periods of missing data will be omitted. If 
missing data represent >10% of observation time (which will be truncated if a participant leaves 
the study early), we will examine distributions of other variables in the dataset to see if they 
differ between those with high/low levels of missingness. We will consider methods to reduce 
bias in the estimate of treatment effect such as including covariates in the main outcomes model. 
 
 
 

23 | P a g e  
 
 
 
Appendix A: Devices 
Apple Watch 
 
 
Apple iPhone 
 
Dexcom G6 Continuous Glucose Monitoring System which includes Sensor and Sensor 
Transmitter 
 
 
Scale 
 
 
 

24 | P a g e  
 
 
 
Appendix B: 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) 
 
5. How often in the last month have you had readings < 70 mg/dl with symptoms?  
Never 
1 to 3 times 

25 | P a g e  
 
 
 
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 mg/dL, 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) 
 
 

26 | P a g e  
 
 
 
Appendix C: Diabetes Distress Scale 
Directions: Living with diabetes can sometimes be tough. There may be many problems and 
hassles concerning diabetes and they can vary greatly in severity. Problems may range from 
minor hassles to major life difficulties.  Listed below are 17 potential problem areas that people 
with diabetes experience. Consider the degree to which each of the 17 items may have distressed 
or bothered you DURING THE PAST MONTH and circle the appropriate number. 
 
Please note that we are asking you to indicate the degree to which each item may be bothering 
you in your life, NOT whether the item is merely true for you.  If you feel that a particular item 
is not a bother or a problem for you, you would circle “1”.  If it is very bothersome to you, you 
might circle a “6”. 
 
I am…… 
Not a 
problem 
A slight 
problem 
A 
moderate 
problem 
Somewhat 
serious 
problem 
A 
serious 
problem 
A very 
serious 
problem 
1. Feeling that diabetes is 
taking up too much of my 
mental and physical energy 
every day. 
1 
2 
3 
4 
5 
6 
2. Feeling that my doctor 
doesn’t know enough about 
diabetes and diabetes care. 
1 
2 
3 
4 
5 
6 
3. Feeling angry, scared 
and/or depressed when I 
think about living with 
diabetes. 
1 
2 
3 
4 
5 
6 
4. Feeling that my doctor 
doesn’t give me clear 
enough directions on how 
to manage my diabetes. 
1 
2 
3 
4 
5 
6 
5. Feeling that I am not 
testing my blood sugars 
frequently enough. 
1 
2 
3 
4 
5 
6 
6. Feeling that I am often 
failing with my diabetes 
regimen. 
1 
2 
3 
4 
5 
6 
7. Feeling that friends or 
family are not supportive 
enough of my self-care 
efforts (e.g., planning 
activities that conflict with 
my schedule, encouraging 
1 
2 
3 
4 
5 
6 

27 | P a g e  
 
 
 
me to eat the “wrong 
foods”). 
8. Feeling that diabetes 
controls my life. 
1 
2 
3 
4 
5 
6 
9. Feeling that my doctor 
doesn’t take my concerns 
seriously enough. 
1 
2 
3 
4 
5 
6 
10. Not feeling confident in 
my day-to-day ability to 
manage diabetes. 
1 
2 
3 
4 
5 
6 
11. Feeling that I will end 
up with serious long-term 
complications, no matter 
what I do. 
1 
2 
3 
4 
5 
6 
12. Feeling that I am not 
sticking closely enough to a 
good meal plan. 
1 
2 
3 
4 
5 
6 
13. Feeling that friends or 
family don’t appreciate how 
difficult living with diabetes 
can be. 
1 
2 
3 
4 
5 
6 
14. Feeling overwhelmed 
by the demands of living 
with diabetes. 
1 
2 
3 
4 
5 
6 
15. Feeling that I don’t have 
a doctor who I can see 
regularly about my 
diabetes. 
1 
2 
3 
4 
5 
6 
16. Not feeling motivated to 
keep up my diabetes self-
management. 
1 
2 
3 
4 
5 
6 
17. Feeling that friends or 
family don’t give me the 
emotional support that I 
would like. 
1 
2 
3 
4 
5 
6 
 
 
 

28 | P a g e  
 
 
 
Appendix D: Sleep quality Scale[24] 
 
 
 

29 | P a g e  
 
 
 
Appendix E: Study completion interview script 
Questions: 
1. What did you call the app? 
2. General understanding of app 
a. If you were telling someone else about the app, how would you describe it? 
b. What do you think is the best feature of the app? 
c. What were the positives and negatives of the app? 
3. Expectations of the app 
a. What were your expectations of the system before you started the trial? 
b. Do you think predicting nighttime lows and providing snack recommendations 
would help you with diabetes management? 
c. Did anything surprise you about the app? 
4. Usability of the app 
a. Which of the issues below was the biggest problem during the study? 
i. The App was confusing to use 
• What were the difficult parts of using the app? Why? 
ii. The app was visually unappealing 
iii. The app crashed 
iv. The app was missing features I consider important 
• What were those features 
b. Rate the following aspects of the app (scale 1 to 5, 5 is best possible score) 
i. Stability 
ii. Navigation 
iii. Functionality 
iv. Look and feel 
5. Trusting the App 
a. How easy was it to trust the predictions and recommendations of the app to avoid 
nighttime low glucose? 
b. Would you use the app right now to help you avoid nighttime low glucose? 
c. Would you use the app outside of the study if you could? 
6. Barriers to Use 
a. What might stop you from wanting to use this system in the future if it was 
available? 
 
 
 
 
 
 
 
Appendix F: Hypoglycemia fear survey 

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32 | P a g e  
 
 
 
 
Appendix G: Bedtime snacks alternatives 
 
DailyDose 
recommended 
snack 
Alternative 1 
(Gluten free) 
Alternative 2 
(Contains 
dairy but is 
gluten, nut, 
and shellfish 
free) 
Alternative 3 
(Contains wheat 
and soy; no 
nuts, dairy, or 
shellfish) 
Aternative 4 
(No gluten, dairy, 
shellfish, or nuts) 
1 bar 
from package 
1 bar 
1 bar 
 
 
 
 
2 bars 
from package 
 
 
 
 
 
1 bar 
 
Low fat fruit 
yogurt 6 oz 
 
 
 
Graham 
crackers 2 
sheets 
 
 
 
 
1 bar 

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Fruit snacks 0.9 oz 
 
 
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