Pilot and Feasibility Trial of HypoPals, a Mobile Health Intervention for Improving Hypoglycemia Self-management in Type 1 Diabetes Adults Using Advanced Diabetes Technologies
Phase: NA
Conditions: Type 1 Diabetes, Hypoglycemia
Sponsor: University of Michigan

Study Title: Pilot Feasibility Study for HypoPals, a Mobile Health 
Program for Improving Hypoglycemia Management 
PI: Yu Kuei Lin, MD 
Protocol ID: HUM00228484 
NCT: NCT05916131 
Document IRB approval date: 7/6/2023 

 
Project Title:  Feasibility trial of HypoPals, a mobile health intervention for improving hypoglycemia self-
management in T1D adults using advanced diabetes technologies 
Protocol Number:  HUM00228484 
Grant number (Agency): K23DK135111 (NIDDK) 
Study status:  Not yet recruiting 
Anticipated Start Date:  June 1st, 2023 
 
List of personnel: 
Name 
Title 
Department 
Role 
Yu Kuei Lin, MD 
Clinical Assistant 
Professor 
Internal Medicine/MEND 
Principal investigator 
John Piette, PhD 
Professor 
Health Behavior and Health 
Education 
Co-investigator 
Nicolle Marinec 
Senior Project 
Manager 
Health Behavior and Health 
Education 
Other (external 
collaborator) 
Jenny Chen 
Research Area 
Specialist Senior 
Health Behavior and Health 
Education 
Research Staff 
Sean Newman 
App Programmer 
Health Behavior and Health 
Education 
Research Staff 
Patrick Neggie 
App Programmer 
Health Behavior and Health 
Education 
Research Staff 
Adam Martin-Schwarze 
Biostatistician 
SABER/Biostatistics 
Biostatician 
Diana Hall 
Clinical research 
project manager 
Internal Medicine/MEND 
Study coordinator 
Emily Hepworth 
Clinical research 
study coordinator 
Internal Medicine/MEND 
Study coordinator 
Annika Agni 
Research Staff 
Family Medicine 
Research Staff 
 
 
 

Protocol Summary 
Background:  Hypoglycemia is a major complication of diabetes, which continues to occur in people living with 
type 1 diabetes (T1D) despite the current standard of care including advanced diabetes technologies. Survey 
and qualitative studies inform that reduced ability to detect hypoglycemia symptoms and unhelpful beliefs 
around hypoglycemia are related to increased risks for developing hypoglycemia in T1D advanced diabetes 
technologies. We have devised a mobile health (mHealth) text messaging behavioral intervention program 
(“HypoPals”) for improving hypoglycemia symptom detection and tailoring unhelpful hypoglycemia beliefs. A 
pilot study is needed to inform the integrity of the mHealth technology, preliminary intervention fidelity and 
acceptability, and effectiveness trial conduct. 
Objective:  Conduct a pilot study of an mHealth hypoglycemia behavioral intervention program to evaluate the 
mHealth technology integrity, preliminary intervention fidelity and acceptability, and the feasibility of the 
effectiveness trial conduct. 
Study design:  This is a pilot feasibility 2x2 factorial design randomized clinical trial at the University of 
Michigan. The study duration will be three years. 
Study population and participants: Registrees of the T1D Exchange, a national T1D patient registry, will be 
approached for recruitment. Adults with T1D, using continuous glucose monitor (CGM) ≥1 year and continue to 
experience ≥1 severe hypoglycemic episode (SHE) OR spending ≥1% of time in level 2 hypoglycemia will be 
recruited. 
Intervention: All eligible participants will undergo a 2-week basic hypoglycemia education. Four possible 
experimental conditions (10 weeks) will be randomly assigned to participants in 1:1:1:1 ratio: (1) Hypoglycemia 
symptom detection training+psychoeducation; (2) hypoglycemia symptom detection training only; (3) 
psychoeducation only; (4) usual care. The entire intervention phase will last 12 weeks. 
Endpoints: Outcomes of mHealth technology integrity (e.g., connectivity to CGM data, message delivery), 
intervention fidelity and acceptability (message reading and acceptability) and trial conduct (e.g., recruitment, 
retention, outcome assessment) will be collected. The primary outcome is the number of people to recruit to 
reach to n=20 completing the intervention. 
 
 
 
 

Scheduled activities: 
 
Events can occur ±1 week of the dates. 
CGM, continuous glucose monitor; EMR, electronic medical records 
 
 
 
 
 
 
 
Pre-screening 
(Pre-consent) 
Recruitment 
Week 0 
(baseline) 
Week 2 
Week 6 
Week 12 
Week 26 
Week 52 
Demographics 
X 
 
 
 
 
 
 
 
Clinical and diabetes history 
X 
 
 
 
 
 
 
 
Severe hypoglycemia history 
X 
 
X 
 
 
X 
X 
X 
CGM data collection 
X 
 
X 
 
 
X 
X 
X 
Eligibility criteria confirmation 
 
X 
 
 
 
 
 
 
Informed consent 
 
X 
 
 
 
 
 
 
Hypoglycemia symptom detection; 
confirmation; beliefs; management 
intention setting; decision and action to 
manage hypoglycemia 
 
 
X 
 
 
X 
X 
X 
Interoceptive awareness 
 
 
X 
 
 
 
 
 
Advanced diabetes technology changes 
 
 
X 
X 
X 
X 
X 
X 
Randomization/Intervention initiation 
 
 
X 
 
 
 
 
 
Feasibility Outcome Evaluation 
mHealth technology integrity outcomes 
 
 
X 
X 
X 
X 
 
 
Intervention fidelity and acceptability outcomes 
Intervention fidelity 
 
 
X 
X 
X 
X 
X 
X 
Intervention acceptability 
 
 
 
 
 
X 
 
 
Trial conduct outcomes 
Feasibility of protocol and recruitment 
conduct 
X 
X 
X 
X 
X 
X 
X 
X 
Feasibility of outcome measurements 
 
 
X 
 
 
X 
 
 
Participation compensation feedback 
 
 
 
 
 
X 
 
 
Safety Evaluation 
Pregnancy Reporting 
 
 
X 
X 
X 
X 
X 
X 
Adverse events reporting 
 
 
X 
X 
X 
X 
X 
X 
Diabetic ketoacidosis reporting and CGM 
hyperglycemia assessment 
 
 
X 
X 
X 
X 
X 
X 
Estimated coordinator time commitment 
(min) 
20 
60 
20 
10 
10 
10 
20 
20 

1.  Introduction 
Background & objectives 
Level 2 hypoglycemia (blood glucose <54 mg/dL) is a dangerous complication of diabetes. Despite using 
advanced diabetes technologies such as continuous glucose monitoring systems (CGMs) and automated 
insulin delivery systems (AIDs), level 2 hypoglycemia continues to impact people living with type 1 diabetes 
(T1D).1-4 Reduced abilities to detect hypoglycemia symptoms5 and unhelpful hypoglycemia beliefs1 are key risk 
behavioral factors leading to developments of level 2 hypoglycemia in this population. However, it remains 
unknown whether hypoglycemia symptom detection training, which helps improving hypoglycemia symptom 
awareness, and psychoeducation, focusing on tailoring unhelpful hypoglycemia beliefs, conducted via mobile 
health technologies for expanding access to these interventions, can effectively improve hypoglycemia self-
management and reduce level 2 hypoglycemia in advanced diabetes technology users. Our long-term goal is 
to develop scalable, personalized interventions for addressing unhelpful patient behaviors that limit the optimal 
use of advanced diabetes technologies for minimizing dangerous hypoglycemia. We plan to, under the 
Multiphase Optimization Strategy (MOST) framework,6 evaluate the impact of mobile health hypoglycemia 
symptom detection training for improving hypoglycemia symptom awareness, and psychoeducation for tailoring 
unhelpful beliefs, for reducing severe and level 2 hypoglycemia, and identify predictors of hypoglycemia 
reduction with each intervention component for intervention personalization with a 2x2 factorial design 
randomized trial (hypoglycemia symptom detection training, on vs. off; psychoeducation, on vs. off). A pilot 
study is needed to inform the integrity of the mHealth technology, preliminary intervention fidelity and 
acceptability, and effectiveness trial conduct. 
Objective: To conduct a pilot study of an mHealth hypoglycemia behavioral intervention program to evaluate 
the integrity of the mHealth technology, preliminary intervention fidelity and acceptability, and the feasibility of 
effectiveness trial conduct such as protocol conduct (e.g., screening, recruitment and retention) and outcome 
measurements. 
Risk/benefits assessment for justifying the study: 
• 
Potential risks: The most likely risk to participants is the time burden associated with participation in 
the study. We do not expect study-related text messages and collections of patient demographics, 
CGM data and patient reported outcomes through self-reporting instruments to significantly increase 
participants’ health risks to higher than they would otherwise experience in their ordinary daily life. 
Other potential risks include the breach of confidentiality or data security ("rare"). Some participants 
may experience distress from the content of text messages about hypoglycemia. Patients will be 
informed that they can stop from participating in the trial if they do not want to continue with the study. 
• 
Potential benefits: An impactful and widely accessible hypoglycemia behavioral intervention program 
can improve hypoglycemia self-management and reduce hypoglycemia and related complications and 
burdens. If this mHealth program is effective, participants may also experience reduction in 
hypoglycemia. 
• 
Assessment: Participants will be exposed to no more than minimal risk while the information gained 
could help develop an impactful program to reduce life-threatening hypoglycemic events. 
 
2.  Study design 
Trial design overview, setting, and schema 
This is a pilot 2x2 factorial design randomized clinical trial at the University of Michigan. All candidates will 
undergo pre-screening and consent procedures prior to recruitment. After recruitment and baseline 
assessment, all participants will undergo randomization and a 2-week basic hypoglycemia education. 
Subsequently, based on randomization results, four possible experimental conditions will be implemented in 
participants in 1:1:1:1 ratio: (1) Hypoglycemia symptom detection training+psychoeducation; (2) hypoglycemia 
symptom detection training only; (3) psychoeducation only; (4) usual care. Each experimental condition will last 
10 weeks. After the end of the intervention, all participants will undergo the 40-week follow-up phase with 
conduct at 26th week and 52nd week to complete the 52-week study. 
  

 
Randomization, allocation, and blinding 
Adaptive randomization with minimization method will be conducted to ensure equal number of participants 
(n=10) will be randomized into the same number of the 4 experimental conditions (i.e., in 1:1:1:1 ratio). The 
randomization will be stratified based on whether the participant have severe hypoglycemia within the year OR 
spending ≥1% of time in level 2 hypoglycemia on CGM, and the status of closed-loop pump use. The 
procedure of randomization will be determined by the study statistician. 
The experimental condition allocation mechanism will be generated by the study statistician and held by the PI. 
When a participant is recruited, the study coordinator will collect the allocation information from the PI and 
assign the allocation to the participant. 
Even randomization errors are not expected, when they occur, we will apply the intention-to-treat principle and 
include the affected participant into the analysis. When needed, we may also work with the Data and Safety 
monitor, who will provide independent, objective assessment, and under the previously published guidance,7 
and consider removing affected participants. 
This study will not use blinding given complete blinding participants and study investigators from the 
intervention (i.e., education content) participants receives will not be possible.  
End-of-study definition 
The end of the study is defined as completion of the 52-week follow-up assessment. 
 
3. Study population 
Eligibility criteria 
• 
Inclusion criteria: 
1. Provision of signed and dated informed consent form 
2. Age 18-70 
3. Self-reported diagnosis of type 1 diabetes for at least 5 years 
4. Previous attendance of structured diabetes education program 
5. Using CGM ≥1 year 
6. Ongoing Dexcom CGM use time ≥70% based on CGM report at screening 
7. Have had experienced ≥1 episode of SH in the past year while using CGMs OR spending ≥1% 
of time in level 2 hypoglycemia at the time of pre-screening 
8. Using cellphone with functionality for sharing real-time data to Dexcom Clarity and receiving 
text messages 
9. Be able to communicate in English (spoken and written) 
10. Willing to comply with all study procedures including sharing CGM glucose information, 
receiving and reading intervention text messages, and completing study questionnaires 
• 
Exclusion criteria: 

1. Active participation in clinical trials on diabetes/hypoglycemia interventions 
2. Pregnancy or planning for pregnancy within a year 
3. Untreated adrenal insufficiency or hypothyroidism 
4. Uncontrolled mental disorder or chronic cognitive dysfunctions (include but not limited to 
uncontrolled schizophrenia, depression and bipolar disorders; learning disability; active alcohol 
and substance dependence; dementia or cognitive impairment independent of hypoglycemia 
Pre-screening, recruitment, and study initiation processes 
We are conducting a REDCap survey (HUM00232351) with the T1D Exchange, a national type 1 diabetes 
patient registry. At the end of the survey, participants will be asked whether they are interested in participating 
additional research including mHealth studies, and if they are interested in participating in other studies, to 
leave their contact information (email or phone number). Survey participants will be pre-screened based on 
their age, diabetes history and CGM use status and history. A candidate list will be created with only survey 
participants who answered ‘yes’ to the question. The candidates will then be directly contacted either through 
email or phone number by our team for recruitment (and T1D Exchange will not be involved in the recruitment 
process or any other study procedures). We will contact the candidate either through email and telephone for 
up to three times. The candidate list will be kept for records about the number of times a candidate is being 
contacted. The study team will check eligibility and discuss with the candidate about the project and answer 
questions before proceeding to consenting. 
For remote consenting, the research team will send REDCap consent form to the candidates and go over the 
consent with the candidates (either through phone or a virtual meeting). The candidate can download a copy of 
the consent form from the REDCap page. Study information including mobile health text messages and the 
need of CGM glucose information sharing will be informed during the consenting process. We will give 
candidate as much time as needed to consider whether to participate in the study. The participant will also be 
encouraged to discuss with others as a part of the consenting process. If the candidate is willing to provide 
informed consent, they will be asked to type down the full legal name on the REDCap page to complete the 
consenting process. Any questions the patient may have will be answered. 
After study enrollment, the randomization will then be completed and the intervention will then be initiated 
based on the experimental condition allocated. 
Pre-screen failure: Pre-screen failures are defined as participants who completed the pre-screening process 
but are not meeting the eligibility criteria. Individuals who do not meet the criteria for participation in this trial 
because of meeting one or more exclusion criteria that are likely to change over time may be rescreened. 
Examples include not using Dexcom CGMs ≥1 year and use of cellphone not compatible with Dexcom CGM 
software. 
Participation compensation 
Participants can receive up to $270 gift card as participation compensation and the compensation will be split 
throughout the study: $30 after completing enrollment, $180 at the end of intervention, $30 after 26-week 
follow-up and $30 after 52-week follow-up. We estimated the appropriate level of compensation to avoid the 
compensation being viewed as coercive. 
 
4. Intervention 
Intervention components 
All interventions will be delivered via mHealth text messages. All participants will receive 2-week text 
messages of basic education about hypoglycemia. Participants may then receive the hypoglycemia symptom 
detection training and/or psychoeducation intervention components or usual care based on the intervention 
assignment. 
• 
Basic hypoglycemia education intervention component.  Daily text messages providing education 
about definitions, risks, and causes of hypoglycemia and hypoglycemia prevention and management 
skills will be provided. The rationale for including this intervention component is to ensure participants 
have at least a basic level understanding of hypoglycemia to control the heterogeneity of diabetes 
education they have received from local diabetes education programs. This component will also define 

the language used to communicate hypoglycemia-related concepts in the remaining program for those 
who receive other intervention component(s). 
• 
Hypoglycemia symptom detection training.  Text messages providing training for improving 
hypoglycemia symptom detection will be delivered after episodes of CGM-determined hypoglycemia 
(glucose level <70 mg/dL consecutively for ≥15 minutes). The training messages will provide (1) 
knowledge about the type of symptoms of hypoglycemia can present with, including body, sense, 
mental and mood changes, and quick self-tests that patients can perform to actively detect mental 
changes during hypoglycemia; (2) the time of the recent hypoglycemia episode and an invitation for 
patient self-recalling of hypoglycemic symptoms during the episode, and; (3) training on developing a 
list of one’s own hypoglycemia symptoms and the habit of self-checking hypoglycemia symptoms when 
receiving CGM hypoglycemia data. These messages were developed based on the concept of the 
Blood Glucose Awareness Training (BGAT) program, which demonstrated that self-evaluating of 
hypoglycemia symptoms can help improve hypoglycemia symptom detection8 and reduce 
hypoglycemia.9 
• 
Psychoeducation.  Daily text messages for tailoring unhelpful hypoglycemia beliefs that were 
identified in our prior survey1 and interview study (manuscript submitted) will be provided. The 
psychoeducation will focus on (1) helping patients identify their own internal motivations for reducing 
hypoglycemia, and; controlling hyperglycemia and social risk perception related to hypoglycemia self-
management (for directing outcome expectancy towards favoring managing hypoglycemia); (2) 
calibrating hypoglycemia risk perception; and; (3) helping patients develop their own hypoglycemia 
management coping strategies (for improving hypoglycemia management coping self-efficacy). These 
messages incorporate the structure and content of a prior hypoglycemia psychoeducation program 
demonstrated to successfully tailor hypoglycemia beliefs and reduce hypoglycemia.10 Behavioral 
changing techniques from motivational interviewing (including decision matrix) and cognitive behavioral 
therapy (including belief challenging with Socratic-style questions, problem-solving, and exposure 
therapy) were also incorporated. Weekly hypoglycemia outcome feedback messages, guided by 
summarized weekly CGM hypoglycemia data, will also be delivered for improving hypoglycemia 
management self-efficacy. We adopted two-way interactive messages for improving engagement with 
and efficacy of the intervention messages.11 Patient-shared hypoglycemia self-management 
experiences were also incorporated to help patients feel understood and more accompanied while 
acquiring field-tested techniques of hypoglycemia self-management.  
(All text messages were developed to deliver intervention contents with positive framed advocacies in 
an autonomy-respected, empowering, and non-oppressive manner.12 ) 
• 
mHealth technology.  We have developed and feasibility-tested13 the mHealth technology with the 
Twilio platform,14 including an application programming interface (API) to receive patient’s glucose 
levels shared via Dexcom Developer15 for sending hypoglycemia symptom detection training messages 
after CGM-determined hypoglycemic episodes and guiding weekly hypoglycemia outcome feedback 
messages to be delivered. This program can also deliver two-way interactive test messages. 
Fidelity measures:  Text message delivery, reception and reading will be checked for fidelity. For text 
message delivery, a log of the text messages (with content and time stamps) delivered to each participant will 
be available on the HypoPals mHealth program website and will be monitored weekly to ensure correctness of 
the content and time delivered during the intervention period. We will contact participants at, 2, 6 and 12 
weeks, either through telephone calls or text messages, to confirm timely reception of these text messages. 
When contacting participants, we will also evaluate self-reported text message reading based on regularity 
(e.g., from right away to ignoring it completely) and completeness (from the whole message to not at all), with 
an adapted mSustain survey.16 A log of participants’ responses to the two-way interactive text messages will 
also be available on the mHealth program website and the rate of responding will also be used for fidelity 
assessment. During the telephone visits at weeks 0, 2, 6, 12, 26 and 52, we will also verbally assess whether 
the participant has changes in diabetes care including receiving additional diabetes and hypoglycemia-related 
interventions. 
Rescue therapy 
Rescue therapy will not be applied to this study as there currently exists no widely available program for 
reducing hypoglycemia. All study subjects will continue receiving their current care from their diabetes 
healthcare providers for hypoglycemia management.  

 
5. Intervention and participant discontinuation 
Discontinuation of study intervention 
The study intervention will be discontinued if: 
• 
The researcher believes that it is not in the participant’s best interest to stay in the study. 
• 
Participant becomes ineligible to participate. 
• 
Participant's condition changes and needs treatment that is not allowed while taking part in the study. 
• 
Participant deviates from or do not follow instructions from the researchers. 
• 
The study is suspended or canceled.  
The reason(s) for discontinuing the participant from the intervention will be documented.  
When a participant discontinues from study intervention but not from the study, remaining study procedures will 
be completed as indicated by the study protocol.  
Discontinuation from the study 
An investigator may discontinue a participant from the study for the following reasons: 
• 
Significant study intervention non-compliance, unless varying compliance is an aspect of the study 
objectives 
• 
Lost-to-follow up (defined as unable to contact subject and unable to obtain CGM data) 
• 
Any event or medical condition or situation occurs such that continued collection of follow-up study data 
would not be in the best interest of the participant or might require an additional treatment that would 
confound the interpretation of the study 
• 
The participant meets an exclusion criterion (either newly developed or not previously recognized) that 
precludes further study participation 
The reason for participant discontinuation or withdrawal from the study will be recorded. Participants who 
discontinue before the completion of the intervention phase will be replaced. No replacement will occur if the 
participants withdraw or lose follow-up during the follow-up phase. 
Loss of follow-up 
A participant will be considered lost to follow-up if s/he fails to be contacted at week 12, week 26 or week 52 
and study staff are unable to contact the participant after at least 3 attempts AND follow-up CGM data were not 
able to be collected. The following actions must be taken if a participant fails to return to be contacted: 
• 
The site will attempt to reschedule the missed evaluations and contact the participant, obtain 
information for better contact time and ways, and ascertain if the participant wishes to and/or should 
continue in the study. 
• 
The site will attempt to collect CGM data through Dexcom Clarity or Developer. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every effort to 
regain contact with the participant (where possible, up to 3 telephone calls, text messages, and emails 
and, if necessary, a certified letter to the participant’s last known mailing address or local equivalent 
methods. These contact attempts will be documented in the participant’s study file.  
• 
Should the participant continue to be unreachable and her/his CGM data can no longer be collected, 
s/he will be considered to have withdrawn from the study with a primary reason of lost to follow-up. 
 
6. Endpoints and Safety Assessments 
To evaluate the feasibility of the study evaluating an mHealth behavioral intervention program for improving 
hypoglycemia self-management, including mHealth technology integrity, intervention acceptability, and trial 
conduct.  
The primary outcome is the number of people to recruit to reach to n=20 completing the intervention. 
mHealth technology integrity outcomes 
• 
Percentage of participants completing the intervention without experiencing major mHealth technology 
glitches (defined as needing to hold the intervention before the glitches are resolved) 

o For technology team/delivery window 
▪ 
Retrieving CGM glucose information to mHealth server (including after transmitter 
changes) 
▪ 
Texting research team when missing CGM data for 3 days 
▪ 
The ability to switching on/off message delivery 
▪ 
Sending messages at right time (including time zone) 
▪ 
Sending messages in the right sequence (including the introduction messages comes 
together) 
▪ 
Notifying study team when participants text ‘Stop’ on receiving messages 
o Specifically for hypoglycemia symptom detection training program 
▪ 
Messages triggering by CGM hypoglycemia (CGM glucose <70 mg/dL x 15 consecutive 
minutes) 
▪ 
Messages indicating the correct time when hypoglycemia develops 
▪ 
Sending messages at selected time points (e.g., 10am, 3pm, 10pm, etc) 
o Specifically for psychoeducation program 
▪ 
Sending correct responding messages and timely sending responding messages (i.e., 
two-way messaging) 
▪ 
Retrieving and calculating current hypoglycemia outcome in the past two weeks 
o For participants 
▪ 
The messages were received at correct times 
▪ 
The messages delivered correct content 
▪ 
Recording responses from patients 
Intervention fidelity and acceptability outcomes  
• 
Intervention fidelity 
o Percentage of times participants will need to hold intervention due to CGM or cellphone 
technology change 
▪ 
Dexcom CGM discontinuation  
▪ 
Change to cellphone type that has no access to Dexcom Clarity 
o Percentage of CGM usage time  
o Percentage of participants reporting reading message content at the end of the intervention (a 
secondary outcome) 
o Percentage of two-way message responded 
o Time to finish the hypoglycemia symptom detection training and/or psychoeducation 
intervention 
• 
Intervention acceptability 
o Percentage of participants finding message content helpful (a secondary outcome) 
o Number of message received per day 
Trial conduct outcomes 
• 
Feasibility of protocol and recruitment conduct 
o Pre-screening:  
▪ 
Percentage of patients undergoing prescreening 
▪ 
Percentage of pre-screened patients eligible  
o Recruitment:  
▪ 
Number of patients contacted (a secondary outcome) 
▪ 
Number of people to recruit to reach to n=20 completing the intervention (primary 
outcome) 
▪ 
Percentage of contacted patient being eligible and consented (a secondary outcome) 
▪ 
Reasons eligible participant for not consenting 
▪ 
Average time delay from prescreening to enrollment 
▪ 
Average time delay from enrollment to intervention initiation 
o Retention: 
▪ 
Rate of participant retention (at 12 weeks) (a secondary outcome) 
▪ 
Rate of participant retention (at 26 weeks) (a secondary outcome) 
▪ 
Rate of participant retention (at 52 weeks) (a secondary outcome) 

▪ 
Percentage of participants discontinuing study intervention 
▪ 
Reasons for participants to be discontinuing study intervention 
▪ 
Percentage of participants discontinued from the study (including the loss of follow-up) 
▪ 
Reasons for participants to be discontinued from the study (intervention duration, 
assessment burdensome, treatment condition, etc)  
o Compensation fairness 
▪ 
Percentage of participants found the compensation fair 
• 
Feasibility of outcome measurements:  
o Percentage of participant changing advanced diabetes technologies during the study 
o Percentage of participants with CGM data collected (at 12 weeks) (a secondary outcome) 
o Percentage of participants with CGM data collected (at 26 weeks) (a secondary outcome) 
o Percentage of participants with CGM data collected (at 52 weeks) (a secondary outcome) 
o Percentage of participants with questionnaires completed at 12 weeks 
o Percentage of participants with questionnaires completed at 26 weeks 
o Percentage of participants with questionnaires completed at 52 weeks 
o Percentage of people finding self-reported instrument having too many questions to answer 
o Percentage of people finding self-reported instrument taking too much time 
o Percentage of people finding self-reported instrument too tiring to complete 
o Other feedback from study coordinators including training protocol 
Safety and adverse events 
• 
This protocol uses the definition of adverse event and classification of adverse event, the relationship 
between the adverse events with the study procedures, and the expectedness of the adverse event 
from 21 CFR 312.32 (a), which could be found on website: 
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=312.32  
• 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention of 
study personnel during scheduled study contacts with participants or upon review by a study monitor. 
All AEs, not otherwise precluded per the protocol, will be captured on the appropriate case report form 
(CRF). Information to be collected includes event description, time of onset, clinician’s assessment of 
severity, relationship to study procedures (assessed only by those with the training and authority to 
make a diagnosis), and time of resolution/stabilization of the event. All AEs occurring while on study will 
be documented appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
• 
Any medical or psychiatric condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s condition 
deteriorates at any time during the study, it will be recorded as an AE.  
• 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the 
event at each level of severity to be performed. Documentation of onset and duration of each episode 
will be maintained for AEs characterized as intermittent. 
• 
Diabetes-related complications including diabetic ketoacidosis are unexpected adverse events that may 
not be related to the study intervention. These adverse events will be monitored but will not be 
reported. If the rate of these adverse events appears to be higher than expected, the study team will 
discuss with study monitor about whether to put the study on hold to decide the next steps. 
• 
Study coordinators will record events with start dates occurring any time after informed consent is 
obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation.  At 
each study visit, the investigator will inquire about the occurrence of AE/SAEs since the last visit.  
Events will be followed for outcome information until resolution or stabilization. 
• 
All SAEs (defined as death, a life-threatening adverse experience, inpatient hospitalization or 
prolongation of existing hospitalization, a persistent or significant disability/incapacity, and other 
important medical events) will be reported to the Data and Safety Monitor. A trained member of the 
study team will be responsible for conducting an evaluation of a serious adverse event and shall report 
the results of such evaluation to the reviewing Institutional Review Board (IRB) as soon as possible, but 
in no event later than 10 working days after the investigator first learns of the event. The NIH will be 
notified if there are IRB actions (such as regulatory hold) taken on the study. 
Pregnancy 
Pregnancy is an exclusion criterion of the study. During the study period, inquiries about whether the 
participant found herself pregnant at the times indiated as the Scheduled Activities table will be conducted 

through telephone or emails. If a participant reports being pregnant, we will manage as participation 
discontinuation as above. 
 
Data and Safety Monitoring Plan (DSMP) 
 
We do not expect the intervention (i.e., behavior-tailoring text messages for improving hypoglycemia self-
management) to significantly increase participants’ health risks to higher than they would otherwise experience 
in their ordinary daily life. Thus, this project may qualify as a “minimal risk” study.  
 
All research team members will complete and maintain up-to-date human subject training certifications 
including the Collaborative IRB Training Initiative (CITI) and Good Clinical Practice (GCP) certifications. The 
entire study protocol, including the DSMP, procedures to protect study participants and their privacy and 
confidentiality, and the patient consenting process, will be approved by the relevant institutional review board 
(IRB) and other regulatory and oversight entities prior to the initiation of any study procedure.  
 
The study team will meet weekly to review study issues. We will maintain a record of protocol deviation and 
review it every 3 months for any unusual patterns. An official review of study data, protocol adherence, and 
safety, including severe adverse events, will be conducted by the PI, the study coordinator and the Data and 
Safety Monitor(s) after every 5 participants have completed the study. If the Data and Safety Monitor(s) have 
serious concerns with participant data or safety integrity, study activities will be halted and plans for addressing 
these issues will be developed to continue the study, or the decision to terminate the study will be made in 
consultation with the IRB. Additional meetings/conferences with the study team/mentors will be made as 
needed to discuss problems and make recommendations as an ongoing process throughout the study. No 
interim analysis will be conducted for this pilot/feasibility study.  
 
Stop rule: The study will be terminated if the risk-to-benefit ratio is higher than expected. 
 
Data Integrity:  Data integrity of the study will be monitored through an electronic data system (REDCap). This 
electronic data system will prompt data entry or show visual signals if there are data missing and to be filled. 
Additional measures (e.g., number range or selection box) will be implemented to minimize data entry errors. 
The database will be tested before its actual use in research. Documentation integrity will also be reviewed 
after every 5 participants have completed the study procedure as discussed above.  
 
Privacy and Confidentiality:  Procedures to protect privacy and confidentiality, such as using unique numeric 
identifiers for subject identification, collecting information limited to the amount necessary for the study, and 
storing data in a HIPPA-compliant database (REDCap), will be implemented. The electronic data will be 
accessible only to investigators and study team members. The data will be available for review by the FDA or 
any other authorized governmental agencies. 
 
Safety Monitoring:  The occurrence of adverse events (AEs) will be sought by non-directive questioning of the 
patients at recruitment and study end. At the time of enrollment, participants will be provided contact 
information for questions or AE reporting. A review of AEs or severe adverse events (SAEs) will take place 
after every 5 participants have completed the study.  
 
Adverse Event (AE) and Serious Adverse Event (SAE) Reporting:  As mentioned in the Safety and Adverse 
Event section.  
 
7. Statistical design 
Statistical hypothesis 
This pilot/feasibility study was not designed to test any hypothesis. Descriptive analysis will be conducted to 
summarize the participant baseline characteristics, preliminary intervention acceptability and fidelity, and trial 
conduct feasibility. 
Sample size determination 
N=20 participants completing the study was determined to demonstrate the feasibility. To ensure we meet this 
goal, we plan to enroll up to N=40 with n=10 into each experimental condition. However, if we reach N=20 
completing the study, we may stop further recruitment. 
Interim and sub-group analysis 

No interim and sub-group analyses will be conducted. 
 
8. Qualification 
Yu Kuei Lin, MD (PI) is an Assistant Professor of Internal Medicine and diabetes/hypoglycemia researcher. He 
has successful experience in evaluating diabetes patients' hypoglycemia status with CGM glucose information 
through survey studies. Dr. Lin will be responsible for the oversight, design, conduct and data collection and 
analysis of this project. 
John Piette, PhD (Co-I) is a Professor of Health Behavior and Health Education and the Director of the 
Michigan Center for Diabetes and Translational Research Intervention and Technology Research Core and an 
internationally renowned mHealth interventionist. He and his mHealth team has supported to develop and will 
assist to maintain the mHealth-CGM program. Dr. Piette will support the trial for feasibility testing the mHealth-
CGM program. 
Nicolle Marinec, MPH (Externa Collaborator) is the Associate Managing Director of the Program for Quality 
Improvement for Complex Chronic Conditions (QUICCC) which is led by Dr. Piette, a Co-Investigator of the 
study. Ms. Marinec manages the University of Michigan mHealth system staff that are part of the study team. 
In her role, she will provide overall management of mHealth system staff as well as support for day-to-day 
mHealth system research activities. Ms. Marinec is employed by the VA Ann Arbor Healthcare System. 
Jenny Chen (Research Staff) is a senor program manager and a part of the University of Michigan mHealth 
system team. She will work with Nicolle to provide management of mHealth system staff as well as support for 
day-to-day mHealth system research activities.  
Sean Newman and Patrick Neggie  (Research staff) is an mHealth programmer and has supported to develop 
the current mHealth-CGM program; he will support the maintenance and refinement of the mHealth-CGM 
system. 
Adam Martin-Schwarze (Statistician) is a biostatician of the Statistical Analysis of Biomedical and Educational 
Research Group unit of the U-M School of Public Health Department of Biostatistics; he will support the 
participant randomization and statistical analysis. 
Diana Hall, MPH (Clinical research project manager) has experience in conducting qualitative studies, 
recruiting participants and supporting the conduct of clinical trials as study coordinator; she will serve as a 
study coordinator and support the administrative tasks, coordination, patient contact/recruitment and outcome 
measures collections in this study. 
Emily Hepworth (Study coordinator) has experiences in conducting clinical studies including recruiting 
participants and collecting study outcomes; she will serve as a study coordinator and support the 
administrative tasks, coordination, patient contact/recruitment and outcome measures collection in this study. 
Annika Agni (Research staff) has experience in interacting with study participants including conducting focus 
group interviews and qualitative data analysis, CGM data collection. Under our supervision, she will serve as a 
study coordinator and support the administrative tasks, coordination, patient contact/recruitment and outcome 
measures collections in this study. 
 
9. Ethics and Dissemination 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for publication. 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, 
this trial will be registered at ClinicalTrials.gov, and results information from this trial will be submitted to 
ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals.  Data 
from this study may be requested from other researchers up to 5 years after the completion of the primary 
endpoint by contacting the PI.  Data user agreement and IRB approval are needed prior to sharing the 
collected data. 

 
10. Study timeline 
Project timeline 
Year 1 
 
 
 
Year 2 
 
 
 
Year 3 
 
 
0-3 
4-6 
7-9 
10-12 
0-3 
4-6 
7-9 
10-12 
0-3 
4-6 
Enrollment 
 
 
 
 
 
 
 
 
 
 
Intervention 
 
 
 
 
 
 
 
 
 
 
Follow-up 
 
 
 
 
 
 
 
 
 
 
Data analysis 
 
 
 
 
 
 
 
 
 
 
 
11. Protocol History 
Version 
Date 
Description of Change  
Brief Rationale 
V1.0 
05/04/2023 
- (initial version) 
 
V1.1 
06/10/2023 
Clarifying loss of follow-up 
definitions, study outcomes and 
adverse events and reporting; 
update study coordinator 
information 
 
V1.2 
07/28/2023 
Clarify randomization time, check 
other additional intervention for 
fidelity evaluation. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
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