TRE in Type 2 Diabetes Mellitus (See Food Study 3)
Phase: NA
Conditions: Type2Diabetes
Sponsor: University of Minnesota

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 1 of 46 
Template Revised On: 11/1/2021 
ANCILLARY REVIEWS 
DO NOT DELETE.  Submit the completed checklist below with your protocol. 
Which ancillary reviews do I need and when do I need them? 
Refer to HRP-309 for more information about these ancillary reviews. 
Select yes or 
no 
Does your study… 
If yes… 
Impact on 
IRB Review 
☐ Yes 
☒ No 
 
Include Gillette resources, staff 
or locations 
Gillette Scientific review and Gillette 
Research Administration approval is 
required.  Contact: 
research@gillettechildrens.com   
Required 
prior to IRB 
submission 
☒ Yes 
☐ No 
 
Involve Epic, or Fairview 
patients, staff, locations, or 
resources? 
The Fairview ancillary review will be 
assigned to your study by IRB staff 
Contact: ancillaryreview@Fairview.org 
Approval 
must be 
received 
prior to IRB 
committee/ 
designated 
review.   
 
Consider 
seeking 
approval 
prior to IRB 
submission. 
☐ Yes 
☒ No 
 
Include evaluation of drugs, 
devices, biologics, tobacco, or 
dietary supplements or data 
subject to FDA inspection? 
The regulatory ancillary review will be 
assigned to your study by IRB staff 
Contact: medreg@umn.edu  
 
See: 
https://policy.umn.edu/research/indide  
☐ Yes 
☒ No 
 
Require Scientific Review? Not 
sure?  See guidance in the 
Investigator Manual (HRP-
103). 
 
Documentation of scientific merit must 
be provided.   
Contact: hrpp@umn.edu  
☐ Yes 
☒ No 
 
Relate to cancer patients, 
cancer treatments, cancer 
screening/prevention, or 
tobacco? 
Complete the CPRC application process.  
Contact: ccprc@umn.edu  
☐ Yes 
☒ No 
 
Include the use of radiation? 
(x-ray imaging, 
radiopharmaceuticals, external 
beam or brachytherapy) 
Complete the AURPC Human Use 
Application and follow instructions on 
the form for submission to the AURPC 
committee. 
Contact: barmstro@umn.edu  
Approval 
from these 
committees 
must be 
received 
prior to IRB 
approval;  
 
☐ Yes 
☒ No 
 
Use the Center for Magnetic 
Resonance Research (CMRR) 
as a study location? 
Complete the CMRR pre-IRB ancillary 
review  
Contact: ande2445@umn.edu  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 2 of 46 
Template Revised On: 11/1/2021 
☐ Yes 
☒ No 
 
Include the use of 
recombinant or synthetic 
nucleic acids, toxins, or 
infectious agents? 
Complete the IBC application via 
eprotocol.umn.edu 
 
These 
groups 
each have 
their own 
application 
process.  
☐ Yes 
☒ No 
Include the use of human fetal 
tissue, human embryos, or 
embryonic stem cells? 
Contact OBAO for submission 
instructions and guidance 
☒ Yes 
☐ No 
Include PHI or are you 
requesting a HIPAA waiver? 
If yes, HIPCO will conduct a review of 
this protocol. 
Contact: privacy@umn.edu  
☒ Yes 
☐ No 
 
Use data from CTSI Best 
Practices Integrated 
Informatics Core? 
 
Formerly the AHC Information 
Exchange (IE)? 
The Information Exchange ancillary 
review will be assigned to your study by 
IRB staff 
Contact: bpic@umn.edu  
Approval 
must be 
received 
prior to IRB 
approval. 
 
These 
groups do 
not have a 
separate 
application 
process but 
additional 
information 
from the 
study team 
may be 
required. 
 
☐ Yes 
☒ No 
 
Use the Biorepository and 
Laboratory Services to collect 
tissue for research? 
The BLS ancillary review will be 
assigned to your study by IRB staff. 
Contact: Jenny Pham 
Pham0435@umn.edu 
☐ Yes 
☒ No 
 
Have a PI or study team 
member with a conflict of 
interest? 
The CoI ancillary review will be 
assigned to your study by IRB staff 
Contact: becca002@umn.edu  
☒ Yes 
☐ No 
 
Need to be registered on 
clinicaltrials.gov? 
If you select “No” in ETHOS, the 
clinicaltrials.gov ancillary review will be 
assigned to your study by IRB staff 
Contact: kmmccorm@umn.edu  
☒ Yes 
☐ No 
 
Require registration in 
OnCore? 
If you select “No” or “I Don’t Know” in 
ETHOS, the OnCore ancillary review will 
be assigned to your study by IRB staff 
Contact: oncore@umn.edu  
Does not 
affect IRB 
approval. 
 
 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 3 of 46 
Template Revised On: 11/1/2021 
PROTOCOL COVER PAGE 
 
 
Protocol Title 
Time Restricted Eating As a Viable Alternative to Caloric 
Restriction for Treating Hyperglycemia in a Population 
with Type 2 (T2DM) diabetes 
Principal 
Investigator/Faculty 
Advisor 
Name: Lisa Chow, MD, MS 
Department: Department: Medicine, Division of Endocrinology, 
Diabetes and Metabolism 
Telephone Number:612-625-8934 
Email Address: chow0007@umn.edu 
Student Investigator 
Name: 
Current Academic Status (Student, Fellow, Resident): 
  
Department: 
Telephone Number: 
Institutional Email Address: 
Scientific Assessment 
Nationally-based, federal funding organizations 
IND/IDE # (if 
applicable) 
N/A. 
IND/IDE Holder 
N/A. 
Investigational Drug 
Services # (if 
applicable) 
N/A. 
Version 
Number/Date: 
V9/2025.03.26 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 4 of 46 
Template Revised On: 11/1/2021 
 
REVISION HISTORY 
 
Revision # 
Version Date 
Summary of Changes 
Consent Change? 
1 
03.22.2022 
1. We clarified additional 
measurements we are taking from the 
V1-3 blood samples. 
2. We clarified the procedures 
involved with getting weekly weights 
from participants via the wi-fi scale. 
3. We noted that the wi-fi scale will 
be given to the participants at the 
brief visit following Visit 1, rather than 
at Visit 1. We wish to make sure the 
participant is eligible to participate in 
the study prior to providing them with 
a wi-fi scale that they can keep. 
 
Yes 
2 
12.22.2022 
1. Upon seeking monitoring services 
from CTSI, we were informed that the 
CTSI will not be monitoring our study 
since we do not meet their 
monitoring criteria. CTSI does not 
monitor studies that do not have an 
IND/IDE/NSR-IDE. We have thus 
removed language referring to CTSI 
monitoring. This modification has 
been made in response to QA Audit 
RNI00009184. 
2. To increase the applicability of the 
dietary interventions to a broader 
population, we plan to increase the 
age criteria from 18-50 years to 18-65 
years and remove the 10 years or less 
duration for diabetes to any duration 
of diabetes. These 2 changes do not 
present any safety concerns to our 
participants. 
Yes. 
3 
04.14.2023 
We have expanded our BMI inclusion 
criteria from BMI:25-35 kg/m2     to 
BMI:25-40 kg/m2 
No. 
4 
03.26.2024 
We have expanded the number of 
participants we may enroll from 100 
to 200, and clarified that we 
anticipate screening 400 individuals of 
Yes. 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 5 of 46 
Template Revised On: 11/1/2021 
which 200 will enroll (sign a consent 
form). 
5 
05.03.2024 
We will use MyChart as a recruitment 
strategy for potentially eligible 
patients of Dr. Chow’s colleagues. 
 
6 
10.14.2024 
We will recruit from the  
Endocrinology clinic by providing 
patients with a QR code that 
describes the study. 
 
7 
10.21.2024 
We will expand the BMI eligibility 
criteria from 25-40 kg/m2 to 25-45 
kg/m2 to facilitate recruitment.  
No 
8 
03.26.2025 
We are including the distribution of a 
flyer to our recruitment strategy.  
No 
 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 6 of 46 
Template Revised On: 11/1/2021 
Table of Contents 
 
1.0 
Objectives .......................................................................................................................... 8 
2.0 
Background ........................................................................................................................ 8 
3.0 
Study Endpoints/Events/Outcomes .................................................................................. 9 
4.0 
Study Intervention(s)/Investigational Agent(s) ................................................................. 9 
5.0 
Procedures Involved ........................................................................................................ 10 
6.0 
Data and Specimen Banking ............................................................................................ 15 
7.0 
Sharing of Results with Participants ................................................................................ 16 
8.0 
Study Population ............................................................................................................. 16 
9.0 
Vulnerable Populations ................................................................................................... 17 
10.0 
Local Number of Participants .......................................................................................... 19 
11.0 
Local Recruitment Methods ............................................................................................ 19 
12.0 
Withdrawal of Participants .............................................................................................. 21 
13.0 
Risks to Participants ........................................................................................................ 22 
14.0 
Potential Benefits to Participants .................................................................................... 23 
15.0 
Statistical Considerations ................................................................................................ 23 
16.0 
Health Information and Privacy Compliance .................................................................. 26 
17.0 
Confidentiality ................................................................................................................. 29 
18.0 
Provisions to Monitor the Data to Ensure the Safety of Participants ............................. 30 
19.0 
Provisions to Protect the Privacy Interests of Participants ............................................. 32 
20.0 
Compensation for Research-Related Injury .................................................................... 32 
21.0 
Consent Process .............................................................................................................. 32 
22.0 
Setting .............................................................................................................................. 34 
23.0 
Multi-Site Research ......................................................................................................... 37 
24.0 
Coordinating Center Research ........................................................................................ 37 
25.0 
Resources Available ......................................................................................................... 37 
26.0 
References ....................................................................................................................... 39 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 7 of 46 
Template Revised On: 11/1/2021 
ABBREVIATIONS/DEFINITIONS 
● TRE/time restricted eating  
● mCC/My Circadian Clock (mCC)  
● CGM/Continuous Glucose Monitoring 
● AE/Adverse Event 
● T2DM/Type 2 Diabetes 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 8 of 46 
Template Revised On: 11/1/2021 
1.0 
Objectives 
1.1 Purpose: We will perform a feasibility study to test our overall hypothesis that 
time restricted eating (TRE) presents a viable alternative to caloric 
restriction for improving glycemic measures and reducing weight in 
overweight/obese patients [BMI:25-45 kg/m2] with metformin-only treated Type 2 
diabetes (T2DM). 
If our hypothesis is proven, our research will have the following impact: 
• Demonstrate the extent to which TRE is a viable alterative to intentional caloric 
restriction in improving hyperglycemia while accounting for weight loss 
• Demonstrate that TRE is acceptable and sustainable relative to intentional 
caloric restriction 
• Provide critical preliminary data supporting a definitive study of TRE to treat 
hyperglycemia in T2DM, which would potentially transform current practice and 
treatment recommendations.     
2.0 
Background 
2.1 Significance of Research Question/Purpose:  
Traditionally, hyperglycemia in patients with T2DM is initially treated with 
metformin, coupled with intentional caloric restriction for weight loss. Sustained 
weight loss by intentional caloric restriction is difficult. Participation in behavioral-
based caloric restriction programs typically reduces total weight by 7-10%, and 
realistically only 30% of participants achieve this goal. Barriers cited include the 
need for multiple face-to-face visits, intervention associated costs, and confusion 
in implementing caloric restriction recommendations. 
In contrast, TRE presents a viable alternative to Caloric Restriction. By its simple 
message and accommodation of dietary preferences, TRE potentially addresses 
many barriers associated with Caloric Restriction. 
2.2 Preliminary Data:  
Our preliminary data reported that TRE (8-hour window for 12 weeks) resulted in 
weight loss (3.7%) while actigraphy-measured physical activity remained 
unchanged and quality of life improved. Our preliminary data also suggests that 
TRE is potentially quite acceptable, with 10-hour TRE continued by 60% of 
participants 16 months later,2 and a ~3.3 kg weight loss still maintained at 36 
weeks post TRE intervention. 
2.3 Existing Literature:  
The effect of TRE on glycemic measures may be more prominent in patients with 
dysglycemia. Although many studies of TRE on glycemic measures have shown 
minimal to modest effects; these studies have all been conducted in patients 
without T2DM. A randomized, crossover study among men with pre-diabetes 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 9 of 46 
Template Revised On: 11/1/2021 
(n=8) had shown that 5-weeks of early TRE (with 6-hour eating window, 
completion of meals at 3 pm) improved insulin sensitivity and beta-cell function 
compared to 12-hour feeding window; this improvement was independent of 
weight loss. 
There are no published randomized trials comparing TRE with intentional 
caloric restriction in patients with T2DM.  
3.0 
Study Endpoints/Events/Outcomes 
3.1 Primary Endpoint/Event/Outcome:  
Aim #1: Compare the effect of TRE vs Caloric Restriction on glycemic measures: 
Hypothesis #1: At the end of Supervised-Intervention (Week 12), the TRE group 
will have similar improvements in Hemoglobin A1c (primary outcome) and other 
glycemic measures [HOMA-IR, HOMA-B, continuous glucose monitoring] 
compared with baseline (Week 0) as the Caloric Restriction group.  
3.2 Secondary Endpoint(s)/Event(s)/Outcome(s): 
Aim #2: Compare the effect of TRE vs Caloric Restriction on weight: Hypothesis 
#2: At the end of Supervised-Intervention (Week 12), the TRE group will have 
similar weight loss compared with the Caloric Restriction group as assessed by in-
person measured weight.  
Aim #3: Compare the effect of TRE vs Caloric Restriction on intervention burden. 
Hypothesis #3: At the end of Supervised-Intervention (Week 12), TRE will cost less 
to administer than Caloric Restriction.. 
Secondary Hypothesis 1.1: At end of Self-Maintained intervention (Week 24), the 
TRE group will have improved glycemic measures compared with baseline (Week 
0) than the Caloric Restriction group. 
Secondary Hypothesis 2.1: During Self-Maintained intervention (Week 12-24), the 
weight trajectory derived from the weekly home-measured weights (wifi-enabled 
scale) will diverge between the TRE and Caloric Restriction groups, with the TRE 
group having less weight regain than the Caloric Restriction group. 
Secondary Hypothesis 3.1: At Week 12 and Week 24, participants in the TRE 
group will self-report higher quality of life and intervention acceptance than the 
Caloric Restriction group. 
4.0 
Study Intervention(s)/Investigational Agent(s) 
4.1 Description:  
For this feasibility study, we will select patients with newly diagnosed/ early-stage 
patients with T2DM by enrolling patients with  metformin-only treated diabetes 
with relevant demographic information [Age: 18-65 years old, BMI:25-45 kg/m2, 
HbA1c: 6.5-8.5%, diabetes]. Informed by our preliminary data, we anticipate 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 10 of 46 
Template Revised On: 11/1/2021 
screening 400 participants of which 200 will be enrolled. Our goal is 28 
participants who completed the study in each group  (total n=56).  
We will perform a 24-week clinical trial of either TRE with an 8-hour eating 
window or intentional caloric restriction (Caloric Restriction) where daily caloric 
intake is reduced by 15%. The study dietitian will meet with the participants 
weekly (over the phone, Doximity, or zoom) for the first 12 weeks of the 
intervention (Supervised-Intervention). For the remaining 12 weeks, the 
participant will maintain their assigned intervention without study dietitian input 
(Self-Maintained Intervention) to assess intervention sustainability.  
 
4.2 
Drug/Device Handling: N/A  
4.3 
Biosafety: N/A 
 
4.4 
Stem Cells: N/A 
4.5 
Fetal Tissue: N/A 
 
5.0 
Procedures Involved 
5.1 Study Design: Figure 1 shows our study design. The screening visit and Visit 1 will 
be completed within 1 month. After completion of Visit 1, participants will be 
randomized to either TRE (8-hour eating window) with ad libitum intake or Caloric 
Restriction (15% reduction of daily caloric intake). Randomization will be stratified 
by sex. For the Supervised-Intervention (Week 1-12) the study dietitian will meet 
with the participants weekly (over the phone, Doximity, or zoom); participants 
will document all food intake using the mCC app and weigh themselves weekly. 
The effects of Supervised-Intervention will be assessed at Visit 2, which will 
include in-person labs and weight. Next, the participants will transition to the 
Self-Maintained Intervention (Week 12-24) where they will continue with the 
mCC app documentation and weekly weights, with no active feedback from the 
study dietitian. Visit 3 will assess the effects of the Self-Maintained intervention. 
Participants will have a brief visit 10 days after Visit 1 to drop off their sensors 
and a brief visit (10 days preceding) before Visit 2 and Visit 3 to have their sensors 
placed. As relevant, pregnancy tests will be performed at Visits 1-3 to exclude 
pregnancy. 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 11 of 46 
Template Revised On: 11/1/2021 
 
5.2 Study Procedures:  
Virtual Screening Visit: At the virtual Screening Visit, the participants will learn 
about the study and will be consented. Participants will utilize an institutionally 
vetted videoconferencing solution (Zoom) available at the University of Minnesota. 
This consumer friendly, HIPAA-compliant cloud-based platform will allow 
participants to securely connect with the study team by mobile phone, tablet, or 
computer. 
At the virtual Screening Visit, the participants will also be taught to use the My 
Circadian Clock (mCC) app, which the study team will help them download (for 
free) onto their smartphone. Next, the participants will use the mCC app to 
document their food intake for at least 1 week. Qualified participants will have an 
eating window (time between 1st food intake and last food take) ≥12 hours and 
demonstrate logging at least 2 meals ≥5 hours apart for 4 or more days per week. 
Similar to our previous work, all participants will have successfully used the mCC 
app (appropriate logging, established eating window) for at least 1 week before 
Visit 1. This run-in period will screen out participants who are unable to use the 
mCC app. 
Randomization will occur after completion of the 24 hour dietary recalls, during the 
brief in-person visit when the sensors are removed (~ 10-14 days after visit 1).  
Visits 1, 2, and 3 will occur at the Clinical Research Unity (CRU): Height and 
weight will be measured. Blood will be drawn in fasting state (at least 8 hours 
from last-reported non-water intake) to measure HbA1c, blood glucose, 
hemoglobin (Hgb), insulin, and lipid profile. Creatinine, AST, ALT, and TSH will also 
be measured at visit 1 for screening purposes. A blood sample from each visit  will 
be stored for future research if the participant agrees to it in the consent form. 
The Actigraph and CGM will be placed on the participant at Visit 1, and returned 
by the participant  at a brief in-person visit 2 weeks later. Participants will have 
the Actigraph and CGM applied during a brief visit 10-14 days prior to Visit 2 and 
Visit 3, and the participants will return the Actigraph and CGM at Visit 2 and Visit 
3.  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 12 of 46 
Template Revised On: 11/1/2021 
3 brief visits will occur at the Delaware Clinical Research Unit (DCRU). The 
removal of the sensors that occur 2 weeks after V1 and the placement of the 
sensors that occur 2 weeks prior to V2 and V3 will occur at the Delaware Clinical 
Research Unit to accommodate convenient participant parking. 
A wi-fi enabled scale will be provided to them at the first brief visit at the DCRU 
after Visit 1. The participants will be able to keep the wi-fi scale.  The coordinator 
will assist the participants in downloading a free app that is associated with the 
wi-fi scale. An app account will be set up using a de-identified ID. The participants 
will weigh themselves weekly using the wi-fi scale until the end of the study (24 
times). Weekly weights will be viewed on the app account and entered directly 
into REDCap.  
 Surveys:  
• SF-36: We will conduct SF-36 Quality of Life Survey at Visits 1, 2, and 3.  
• 
Hunger/Appetite Surveys: We will use standardized visual analog scales 
to assess the effects of the interventions on hunger and appetite. 
• 
Acceptability of intervention: We will conduct surveys (Visit 2, Visit 3) to 
assess the participant’s satisfaction with intervention, including their views 
on self-maintenance. Participants will be asked about their perceptions of 
the intervention’s strengths/weaknesses, willingness to continue and 
willingness to recommend. We will also send follow-up email surveys at 1 
and 3 months post-Visit 3 to assess sustainability. 
 
 
 
 
 
 
Supervised Intervention Week 1-12: 
For the Supervised-Intervention (Week 1-12), all participants document all eating 
occasions using the mCC app and will have weekly Zoom-based individual 
counseling session with the study dietitian.  In addition, all participants will weigh 
themselves weekly on the wi-fi scale. 
• Time Restricted Eating (TRE)   
For the TRE group, each participant will self-select a daily 8-hour eating 
window. The study dietitian will enter this interval into the mCC app and 
will instruct the participants to adhere to this eating window during the  
24 week intervention. This 8-hour window was established by Dr. Panda 
and our previous work.  During the eating window, participants may eat 
ad libitum, without restrictions and per personal preference. They should 
also take their medications that need to be taken with food during this 
time period. Outside the eating window, only water and medications will 
be allowed. If a particular medication requires co-administration with food 
outside the eating window, this will also be allowed. During Supervised-
Intervention (Week 1-12), the study dietitian will review the mCC logs 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 13 of 46 
Template Revised On: 11/1/2021 
weekly for tailored feedback; this feedback will complement the dietitian’s 
provision of strategies to support maintaining the eating window. This 
feedback will be given either a virtual visit ( by Zoom) or a telephone visit, 
as per pt preference.   
• Intentional Caloric Restriction (Caloric Restriction) 
The Zoom-based individual weight loss counseling intervention is based on 
state-of-the-art behavioral weight loss treatment programs as previously 
described in the literature. Similar to our current R01, we will have the 
dietitian create a meal plan using the exchange system. The participant 
will use the exchange system to achieve the goal 15% reduction of caloric 
intake. The 15% reduction was selected as recent literature1 suggest that 
TRE with ad libitum intake reduces caloric intake by ~270 to 300 kcal/day. 
The 15% caloric restriction is similar to the 11.9% caloric restriction 
achieved by the CALERIE-2 study. 
All eating occasions will be logged using the mCC app. The study dietitian 
will review the foods recorded in the mCC app to personalize 
recommendations. The study dietitian will conduct weekly Zoom-based 
meetings with the participant during the Supervised-Intervention (Week 
1-12). The Caloric Restriction program is based on a conceptualization of 
effective weight management that emphasizes 1) identifying behaviors in 
need of change, 2) setting goals for change, 3) monitoring progress, 4) 
modifying environmental cues to facilitate change, and 5) modifying 
consequences to motivate change. Session components will include: 1) 
weekly weighing via wifi-enabled scale; 2) discussion of progress and 
challenges; and 3) discussion of scheduled session topic. Session content 
over time includes information on a variety of strategies participants can 
use to achieve their caloric goals including low energy density choices and 
recipe modification. Skills required to make appropriate dietary changes 
will be modeled, practiced, and reinforced throughout the program. To 
facilitate goal adherence, use of preset menus with associated shopping 
lists will be encouraged. 
Self-Maintained Intervention (Week 12-24): All participants will continue 
documentation with the mCC app with no active feedback from the study 
dietitian. In addition, all participants will weigh themselves weekly on the wi-fi 
scale. 
After Visit 3, the dietician will provide complimentary dietary counseling to all 
participants based on mCC dietary log collected over the preceding 24 weeks. This 
is to increase study retention through Week 24 of the program.   
Procedures: 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 14 of 46 
Template Revised On: 11/1/2021 
My Circadian Clock (mCC): The mCC app will be used by all participants to log 
food and beverage intake for the entire duration of the study. We have used this 
app with our previously IRB approved study  (1701M06001) as well as our 
ongoing IRB approved protocol ( STUDY00008545)  This app was designed and is 
currently maintained by Dr. Panda‘s group. The app is freely available on the 
iPhone or Android platform  and allows a participant to use the phone camera to 
take a picture of the specific food or beverage prior to eating. The time stamp and 
the location are transferred de-identified to a HIPAA compliant data server, which 
is linked back to the individual by the study team. Participants are randomly 
reminded (1-2 times per day) to input food intake and cannot view their food 
record once entered.  
We selected the mCC app to assess the eating window and monitor intervention 
compliance because of its research-orientation. Many commercially-based, 
consumer-oriented mobile food records (ie. My FitnessPal) are available. 
However, several reasons limit the research relevance of these commercially-
based apps: 1) Unknown validity; 2) Data (e.g. nutrient intake estimates) 
provision cannot be customized to our needs; 3) Restrictions on data availability 
for research purposes due to conflicting commercial interests, and 4) Inconsistent 
rigor with regards to data privacy and security (i.e. not HIPAA compliant). In 
contrast, the mCC app has been created by Dr. Panda (Co-I) for research 
purposes, meeting research level requirements (HIPAA compliant, data 
encryption), full metadata access, and full access for redesigning the software. 
Many studies, including our own, have used the mCC app.  
Sleep and Activity Measurements: We will use the Actigraph Link to quantify 
physical activity, sleep duration, and sleep quality using actigraphy for a 10 day 
period at Visits 1, 2 and 3. This accelerometry-based sensor has been used in 
clinical research to objectively quantify physical activity, sleep duration and 
efficiency. At Visit 1, we provide the Actigraph Link to the participant (with a brief 
visit for removal 2 weeks later). Ten days prior to Visit 2 and Visit 3, participants 
will come in for a brief visit so that the sensor can be applied, followed by 
removal of the sensor at Visit 2 and Visit 3.   
Continuous Glucose Monitoring (CGM): We will use a blinded CGM (Dexcom 
G6 Pro or Freestyle Pro) to evaluate the intervention’s effect on the daily 
glucose profile (similar to our previous work) for a 10 day period at Visits 1, 2 
and 3. The CGM will be applied to the participant at Visit 1 (Brief visit for removal 
2 weeks later) and by a brief visit to apply the sensor 10 days prior to Visit 2 and 
Visit 3. The CGM measures interstital glucose every 5 minutes over 10 days to 
characterize the participant’s glycemic profile. 
24 hour dietary recall: Three interviewer-administered 24-hour dietary recall will 
be collected at baseline (the two week period immediately following Visit 1), Week 
10-12 (the two week period immediately preceding Visit 2) and Week 22-24 (the 
two week period immediately preceding V3) In total, this will be 9 recalls per 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 15 of 46 
Template Revised On: 11/1/2021 
participant. The recalls will be conducted over the telephone by trained and 
certified University of Minnesota Nutrition Coordinating Center (NCC) staff. The 
recalls will be unannounced (unscheduled within the measurement period) to 
minimize measurement reactivity. The NCC staff will be blinded to intervention 
assignment. The Nutrition Data System for Research, a dietary analysis software 
program developed by the NCC, will be used to collect the dietary recalls. We will 
use the multiple-pass interview technique to prompt for complete food and 
beverage recall and descriptions. Using 24-hour dietary recall data, we will 
calculate average intake of calories, macronutrients and the Healthy Eating Index 
score. These results will be compared relative to baseline and between 
interventions. 
Wi-fi scale: We will provide participants with a wi-fi smart scale to conduct the 
weekly weights at home. They will be able to keep this scale after completion of 
the study. A free mobile app is associated with the wi-fi scale. This will be 
downloaded to the participant’s smartphone.  An app account will be created 
using a de-identified ID and log in information. When participants weigh 
themselves at home, the weight will be recorded to the de-identified app account 
online. The study coordinator can view the weight online using the de-identified 
ID. They will then enter the weight into REDCap. When the participant has 
completed the study, they will be instructed to change their app ID and log in 
information so that it can no longer be accessed by the study. 
To address Aim 3, we will measure the staff time involved to deliver the 
interventions. We will measure intervention session time by having the dietitian 
record the number of minutes spent preparing as well as the in-session time in the 
REDCAP database, similar to previous work. We will track the overall intervention 
staff FTE needed. Interventionist time will be converted to costs by multiplying by 
an appropriate wage rate, which will be the median salary for interventionists with 
similar qualifications. Time costs for the interventionist will be varied in a 
sensitivity analysis, since multiple occupational classes, with varying salaries, 
could deliver the intervention. In addition to staff time, we will estimate the monthly 
costs required to provide and maintain the mCC app. 
5.3 Study Duration: It is anticipated that study participants will be in the study for 
approximately 7 months. 
 
5.4 Use of radiation: N/A  
5.5 Use of Center for Magnetic Resonance Research: N/A  
6.0 
Data and Specimen Banking 
 
With participant permission as noted on the consent, we will save deidentified blood 
samples for future analysis (not genetic testing); participants can withdraw their consent 
at anytime.  The purpose is to leverage the participant’s participation in the study by 
saving samples for future biomarker analysis which may be predictive of study 
outcomes.  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 16 of 46 
Template Revised On: 11/1/2021 
 
7.0 
Sharing of Results with Participants 
7.1 Each participant’s individual results will be provided to the specific individual. The 
results will otherwise be analyzed using de-identified data for presentation at 
national meetings and publication in relevant journals. 
7.2 Sharing of genetic testing: N/A 
7.2.1 Disclosure of results: N/A  
7.2.2 If returning results to participants: N/A 
  
7.2.3 Future analysis of genotypes: N/A  
8.0 
Study Population 
8.1 Inclusion Criteria: Overweight/obese adults with metformin-only treated T2DM 
[Age: 18-65 years old, BMI:25-45 kg/m2, HbA1c: 6.5-8.5%, diabetes]. Self-
reported weight must be stable [±5 pounds] for at least 3 months prior to the 
study. Owns a smartphone.  
8.2 Exclusion Criteria: Active or anticipated pregnancy during the study, T2DM treated 
with medications other than metformin, or presence of eating disorders as noted 
by screening survey. 
8.3 Screening: The screening phone call will introduce the study (see phone script), 
review study eligibility (including a 5 question survey to screen for disordered 
eating) and include a verbal consent for fasting.  
We will request a waiver of documentation of consent during the phone 
screening.   
The Screening Visit (Visit 0) will be a virtual visit using Zoom or Doximity. 
Informed consent will be obtained by the study team. The entire consent 
document will be reviewed, including all study procedures and expectations, 
risks, benefits, and what volunteering means. Candidates will be given time to 
read the consent, ask questions, and to take the consent home to review if 
requested. Height and weight will be self-reported. An eConsent/HIPAA form will 
be developed in REDCap and provided to potential participants for esignature.  
The current UMN consent/HIPAA form will include Salk approved consent 
language for the mCC app usage. The signed consent/HIPAA form will be 
applicable for both UMN and Salk procedures. Once the participant has signed 
the consent/HIPAA form, the mCC app will be downloaded from the iTune 
Appstore or Google Play appstore. After activation of the app and device ID 
authentication, the study code cannot be concurrently used with another device. 
A unique random alphanumeric character string will be used to encode the user 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 17 of 46 
Template Revised On: 11/1/2021 
and only that identifier will be used to transmit encrypted data between the 
device and a HIPAA compliant cloud server.  
Once consented using the site consent form and the online app consent form, the 
subject will be scheduled for their baseline appointment (Visit 1).  
At the virtual Screening Visit, the participants will be consented, learn about the 
study and be taught on mCC app usage. Next, the participants will use the mCC 
app to document their food intake for at least 1 week. Qualified participants will 
have an eating window (time between 1st food intake and last food take) ≥12 
hours and demonstrate logging at least 2 meals ≥5 hours apart for 4 or more 
days per week. 
9.0 
Vulnerable Populations 
 
9.1 Vulnerable Populations:  
 
Population / Group 
Identify whether any of the 
following populations will be focus 
of the research (targeted), 
included but not necessarily the 
focus or excluded from 
participation in the study. 
Children 
N/A 
Pregnant women/fetuses/neonates 
N/A 
Prisoners 
N/A 
Adults lacking capacity to consent 
and/or adults with diminished 
capacity to consent, including, but 
not limited to, those with acute 
medical conditions, psychiatric 
disorders, neurologic disorders, 
developmental disorders, and 
behavioral disorders 
N/A 
Non-English speakers 
N/A 
Those unable to read (illiterate) 
N/A 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 18 of 46 
Template Revised On: 11/1/2021 
Employees of the researcher 
N/A 
Students of the researcher 
N/A 
Undervalued or disenfranchised 
social group 
N/A 
Active members of the military 
(service members), DoD personnel 
(including civilian employees) 
N/A 
Individual or group that is 
approached for participation in 
research during a stressful situation 
such as emergency room setting, 
childbirth (labor), etc. 
N/A 
Individual or group that is 
disadvantaged in the distribution of 
social goods and services such as 
income, housing, or healthcare. 
N/A 
Individual or group with a serious 
health condition for which there are 
no satisfactory standard treatments. 
N/A 
Individual or group with a fear of 
negative consequences for not 
participating in the research (e.g. 
institutionalization, deportation, 
disclosure of stigmatizing behavior). 
N/A 
Any other circumstance/dynamic 
that could increase vulnerability to 
coercion or exploitation that might 
influence consent to research or 
decision to continue in research. 
N/A 
 
9.2 Additional Safeguards, if any, to ensure inclusion is appropriate:  
Undervalued/disenfranchised/Active members of the military and DoD 
employees will not be identified and information will not be collected as to a 
patient’s status. This research does not add risk to this group. We will not 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 19 of 46 
Template Revised On: 11/1/2021 
specifically recruit from this population but will not exclude a participant from 
this population if they volunteer and are eligible for the study. 
 
9.3 If research includes potential for direct benefit to participants, provide rationale 
for any exclusions indicated in the table above: N/A 
10.0 Local Number of Participants 
10.1 Local Number of Participants to be Consented: We will screen approximately 400 
individuals. We anticipate up to 200 of these individuals will be consented 
(enrolled). Our goal is to have 28 participants who completed the study in each 
group (total n=56). Qualifying participants will proceed with Visit#1. 
11.0 Local Recruitment Methods 
11.1 Recruitment Process: Our recruitment strategy will be multimodal, including 
recruitment through the electronic health record, online advertisement, 
newspaper, television and radio public interest stories; public service 
announcements; solicitation of health care provider referrals; direct mailings to 
potential participants; advertisements; small print media, registration in 
StudyFinder and Clinicaltrials.gov. A study flyer will also be distributed to some 
diabetes-related external groups, such as the ADA MN Chapter. If these groups 
are willing, they will in turn either post the flyer on their website or distribute to 
their member base.  
Based on our success with our current NIH funded recruitment (Chow) we will 
rely heavily on using the electronic health record (EPIC) for recruitment. The 
University of Minnesota is a partner of the Fairview Health System which has 
used EPIC since 2011. As of May 2021, the Fairview EPIC system has 3.3 million 
living patients, with 19465 research-eligible patients with T2DM treated by 
metformin alone. This constitutes a pool of ~20000 patients with T2DM who are 
eligible for study recruitment. Based on our previous experience, we anticipate a 
10% response rate to this targeted, recruitment approach. 
We will send study invitation letters in batches to potentially eligible MHealth 
Fairview patients using the Fairview Research Recruitment Services (FRRS). Study 
staff will only call those individuals who respond to the study invitation letter that 
they are interested in learning more about the study. After providing more 
information about the study, if an individual remains interested, a Zoom virtual 
screening visit will be arranged.  
The patients at M Health Fairview – Minneapolis Diabetes & Endocrinology Clinic, 
where Dr. Chow works, may also be screened for eligibility. A study invitation letter 
may be sent out by Dr. Chow’s faculty colleagues in this clinic as well as Dr. Chow’s 
colleagues in the M Health Fairview practice. As with the general Fairview letters, if 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 20 of 46 
Template Revised On: 11/1/2021 
a patient responds that they would like to find out more information, our study staff 
will call them.  
 
In addition to screening for eligible patients at the Minneapolis Diabetes & 
Endocrinology Clinic, each patient seen at the clinic will be provided information 
about this study via a QR code that will be attached to their after-visit summary. This 
clinic-based recruitment effort will involve several IRB approved studies in 
Endocrinology.  An IRB approved QR code for each study, including our study, will 
be provided to clinic patients as a part of their after-visit summary. 
 
MyChart messages may also be sent out to potentially eligible patients of Dr. Chow’s 
colleagues. The study coordinator will inform the FRRS of these potentially eligible 
patients and FRRS will send out the My Chart messages via EPIC who have greed to 
be contacted for research purposes. From MyChart, patients will be directed to call 
or email the coordinator if they are interested in learning more about the study. 
Alternatively, as part of the embedded functionality of MyChart, there are 2 buttons 
that a patient can click on: the “I’m Interested” blue button or the “No, thank you” 
orange button. When the patient clicks on the “I’m Interested” button, a notification 
will be sent to the PI’s or coordinator’s EPIC In-Basket. The PI or the coordinator will 
respond to the patient with an EPIC response message inviting them to call or email 
the coordinator.  
 
If recruitment is challenging, we will engage other Twin Cities health systems, 
such as HealthPartners or Allina Health Systems, for recruitment and consider 
expanding to patients with T2DM treated by diet only. 
11.2 Identification of Potential Participants: Participants may self refer in response to 
any public advertisements used, such as posters or social media, or through word 
of mouth. 
The University of Minnesota is a partner of the Fairview Health System which has 
used EPIC since 2011. As of May 2021, the Fairview EPIC system has 3.3 million 
living patients, with 19465 research-eligible patients with T2DM treated by 
metformin alone. This constitutes a pool of ~20000 patients with T2DM who are 
eligible for study recruitment. Based on our previous experience, we anticipate a 
10% response rate to this targeted, recruitment approach. BPIC will identify 
potential participants by applying the eligibility criteria for the study to the EHR 
record. The first screen will encompass the most recent 6 months review of the 
EHR. Subsequent screens will include only the past month review of eligible 
participants. Patients who have opted out of research in their Epic EHR will be 
excluded from consideration for participation. 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 21 of 46 
Template Revised On: 11/1/2021 
11.3 Recruitment Materials:  
Participants may self-refer if they become aware of the study through 
recruitment materials or word of mouth referrals. [A letter about the study may 
be sent to potential participants, asking them to contact the study coordinator if 
they are interested.] Individuals who respond to the recruitment materials will be 
taken through a phone-screening questionnaire. If following the phone screen the 
potential participant is eligible and interested, the study coordinator will schedule 
the screening study visit. 
The study may utilize social media accounts such as (Facebook, Twitter, 
Instagram, independent website, etc.) to create an informative space about 
research opportunities and information for patients with obesity or prediabetes. 
Describe materials that will be used to recruit participants.  
11.4 Payment: Participant compensation will be tied with retention. For the screening 
visit, the participants will be paid $15. For each completed study visit, the 
participant will be paid $50.Total compensation will be $165 for completion of 
the entire study. Each participant will keep their wi-fi enabled scale, which has an 
estimated value of $90. Additional retention techniques will include: 1) Upfront 
notice during phone screening and screening visit about time needed for study 
commitment (7 months duration) 2) Prorated compensation, 3) Tailoring dietary 
interventions to improve palatability while remaining within the parameters of 
the intervention. 
12.0 Withdrawal of Participants 
12.1 
Withdrawal Circumstances:  
• Stopping rules met 
• Participant request 
• Per judgement of PI 
12.2 
Withdrawal Procedures: If the participants want to discontinue their dietary 
intervention, we will offer the following options in a sequential fashion: 1) Address any 
limiting factors that may prevent program completion, 2) Move the final assessment 
sooner to be performed at the time of dropping out, 3) Continue data collection as 
intensively as possible given the participant’s preferences. We will also collect reasons 
for drop out (i.e. time/duration, transportation, side effects, perceptions of efficacy, 
interaction with staff) to use as potential covariates in the statistical model.  In terms of 
missing data, results from the last observation carried forward as well as multiple 
imputation analysis. For the final analysis, intention to treat analysis and per-protocol 
analysis (analysis in those who completed the protocol) will be performed. 
12.3 Termination Procedures:  
This will be the same as the withdrawal procedures as previous described. 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 22 of 46 
Template Revised On: 11/1/2021 
13.0 Risks to Participants 
13.1 
Foreseeable Risks: There will be minimal physical risks associated with the study 
as described in next section. The seriousness of these risks is low. The risks to the 
subjects arise from using established laboratory techniques (Venipuncture, Actigraph 
activity monitor, CGMs). 
All adverse events (AEs) must have their relationship to study intervention assessed by 
the clinician who examines and evaluates the participant based on temporal 
relationship and his/her clinical judgment. The degree of certainty about causality will 
be graded using the categories below. In a clinical trial, the study product must always 
be suspect. 
 
• 
Related – The AE is known to occur with the study intervention, there is a 
reasonable possibility that the study intervention caused the AE, or there is a temporal 
relationship between the study intervention and event. Reasonable possibility means 
that there is evidence to suggest a causal relationship between the study intervention 
and the AE. 
• 
Not Related – There is not a reasonable possibility that the administration of 
the study intervention caused the event, there is no temporal relationship between the 
study intervention and event onset, or an alternate etiology has been established 
 
Study Procedure 
Risk 
Likelihood/seriousness/mitigation 
Phone screening 
Breach of confidentiality 
Low/Low. We will ask questions related to health, 
fitness, and eligibility for the study. Data will be 
stored on password protected computer in locked 
area. 
Periods of fasting 
Hunger, lightheadedness 
Low/Low. This will be kept to less than 24 hrs. 
Adequate fluids (ie water) will be given to minimize 
dehydration. 
History data 
Incidental findings, breach of 
confidentially 
Low/Low. We will exclude subjects if history is 
clinically relevant. 
Venipuncture lab 
tests 
Incidental findings,  
Transient 
pain/bleeding/bruising; 
High/Low. This is a standard blood draw and total 
amount of withdrawn blood will be held to IRB 
guidelines. 
CGM 
Rash on Skin, irritation to 
skin from adhesive pads, 
incidental findings 
Low/Low. The CGM  results will be blinded to the 
participant. The goal is to monitor glycemic 
fluctuations with exercise. If significant 
hyperglycemia or hypoglycemia is noted after 
unblinding, the patient and their primary provider will 
be notified for further evaluation and management.  
Actigraphy derived 
sleep and physical 
activity data 
Rash on Skin 
Low/Low. Noninvasive measurement of sleep and 
activity data by wearing Actigraph Link on wrist for 
up to 14 days 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 23 of 46 
Template Revised On: 11/1/2021 
 
13.2 Reproduction Risks: N/A 
13.3 Risks to Others: N/A  
14.0 Potential Benefits to Participants 
14.1 Potential Benefits: There are no guarantee of benefits. However, there is 
potential benefit to the human subjects would be weight-loss with the dietary 
intervention. Since we are deliberately enrolling obese, insulin resistant humans, 
their physical health may benefit from any observed weight loss. The subjects are 
allowed to withdraw from the study at any time per their request or per the 
judgment of the investigator. 
 
15.0 Statistical Considerations 
15.1 Data Analysis Plan:  
Generalized linear mixed effects models will be used to evaluate differences 
between the groups (Caloric Restriction,TRE) in subject specific changes for 
glycemic measures (Aim#1); weight (Aim#2); quality of life (Aim#3); physical 
activity, sleep quality, and sleep duration from accelerometer data (Exploratory 
Aim 2.1); and 24-hour dietary recall data during Supervised-Intervention (Week 1-
12) and Self-Maintained Intervention (Week 12-24). We will use similar models to 
compare differences in acceptability and compliance (Exploratory Aim 3.1) 
between the groups at the end of Supervised-Intervention (Week 12) and at the 
end of Self-Maintained intervention (Week 24). These models will capture subject 
specific changes across the full study period (Week 1-24), Supervised-Intervention 
(Week 1-12) and Self-Maintained Intervention (Week 12-24).   
15.2 Power Analysis:  
For this feasibility study, the primary objective is evaluating the non-inferiority of 
TRE compared to Caloric Restriction on HbA1c during the 12 week Supervised-
Intervention (Aim#1) with a secondary objective of evaluating the non-inferiority 
of TRE compared to Caloric Restriction on weight loss (Aim#2). The sample size 
was chosen to have adequate power to establish non-inferiority for both 
outcomes.  
  In our preliminary data, administrating TRE in patients without T2DM, the 
weight loss from baseline to 12 weeks was 3.6 kg(1.9) for the TRE group and 1.5 
Dietary Recall 
Breach of confidentiality 
Low/Low. Study staff will call participants and ask 
about dietary intake for the last 24 hours. The actual 
call will be unannounced but within a specified 2 
week window. Participant will be aware of the 2 week 
window. This will occur 9 times during the study.  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 24 of 46 
Template Revised On: 11/1/2021 
kg(2.4) in the control group, with no improvement in HbA1c.  In a very small 
sample of patients with T2DM in a different study,(Section 3.2.3) the decline in 
weight and HbA1c from baseline was even more pronounced [weight loss: 7.0 
kg(3.1), decrease in HbA1c: 0.93% (0.41)] The effect of lifestyle-based weight-loss 
interventions (diet and physical activity) among adults with T2DM is highly 
variable across studies.4 A meta-analysis of lifestyle interventions in patients with 
T2DM estimated a pooled within-group weight loss of 3.41 kg (95% CI 1.79 to 5.04 
kg) among nine studies with intervention duration ranging from 16 weeks to 9 
years, and a pooled within-group change in HbA1c of −0.38% (95% CI: −0.67, 
−0.09%) among six studies with intervention duration ranging from 6 months to 1 
year.  
        While this preliminary data indicates that TRE may, in fact, be superior to 
Caloric Restriction in increasing weight loss and improving glycemic control 
among individuals with T2DM, we will conservatively power our study as a non-
inferiority study. Using a non-inferiority margin for difference in change in HbA1c 
from baseline to 12 weeks of 0.3% (80% of the expected effect size for Caloric 
Restriction compared to control), a 2-sided 95% confidence interval to establish 
non-inferiority, and assuming a standard deviation in change in HbA1c of 0.4%, a 
total of 56 patients (n=28 per group) would provide 80% power for the analysis of 
the primary endpoint. This sample size will also give sufficient power (80%) for 
establishing non-inferiority with regards to weight loss using a non-inferiority 
margin for difference in change in weight from baseline to 12 weeks of 1.5 kg (the 
expected change in weight for patients not receiving an active intervention, and 
44% of the expected effect size for Caloric Restriction compared to control), 
assuming a standard deviation in change in weight of 2 kg. 
15.3 Statistical Analysis:  
Generalized linear mixed effects models will be used to evaluate differences 
between the groups (Caloric Restriction,TRE) in subject specific changes for 
glycemic measures (Aim#1); weight (Aim#2); quality of life (Aim#3); physical 
activity, sleep quality, and sleep duration from accelerometer data (Exploratory 
Aim 2.1); and 24-hour dietary recall data during Supervised-Intervention (Week 1-
12) and Self-Maintained Intervention (Week 12-24). We will use similar models to 
compare differences in acceptability and compliance (Exploratory Aim 3.1) 
between the groups at the end of Supervised-Intervention (Week 12) and at the 
end of Self-Maintained intervention (Week 24). These models will capture subject 
specific changes across the full study period (Week 1-24), Supervised-Intervention 
(Week 1-12) and Self-Maintained Intervention (Week 12-24).   
We will evaluate whether weight loss is associated with a larger improvement in 
glycemic control for individuals assigned to TRE (Exploratory Aim 1.1) by testing 
the three-way interaction between study visit (categorical value), change in 
weight (% of baseline value), and treatment assignment in the previously 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 25 of 46 
Template Revised On: 11/1/2021 
described mixed effects model. If the three-way interaction is not significant, it 
will be removed from the model and we will evaluate the impact of TRE on 
glycemic changes accounting for weight loss.   
We will use linear mixed effects models to test the relationship between eating 
habits and sleep by using the average sleep duration/quality using the Actigraphy-
based evaluation period and corresponding average eating habits. We will adjust 
for treatment effect and/or temporal changes if those effects are identified as 
significant in the primary analysis of group specific differences in change in sleep 
measures. 
As all participants will weigh themselves weekly, we will investigate temporal 
trends in weight change using a mixed effects model. This model will be 
constructed using linear slopes with a change point at the start of the Self-
Maintained Intervention. We will test whether weight trajectories (slopes) 
diverge between the treatment arms during Self-Maintained Intervention by 
testing the appropriate interaction term in the model. 
To compare intervention burden between groups (Aim#3) total intervention time 
(study staff time) and costs (staff FTE times salary and mCC app costs) will be 
compared between interventions using t-tests.    
We will check data distributions before conducting statistical tests and will 
transform the data if the normality assumption is not met. Logistic models will be 
used in place of linear models for binary data.  We will include relevant clinical 
factors into our models (including sex, age) to evaluate their influence on change 
in weight, glycemic measures and quality of life. Secondary analyses will be 
performed to examine the association between achieved fasting duration and 
pre-post change in outcomes. These models will include effects of achieved 
fasting duration, treatment group, and the interaction between both effects. We 
will use imputation analysis to account for missing data. Intention to treat 
analysis and per-protocol analysis will be performed. Analyses will be performed 
in R or SAS (Version 9.4, SAS Institute. Cary, NC).  
15.4 Data Integrity:  
1. Rigor: Recruitment of participants will be performed using the defined 
inclusion/exclusion criteria, with particular efforts devoted towards even 
distributions of men/women and inclusion of minority populations. Data collected 
at the initial and final study visits will be entered by research staff into Research 
Electronic Data Capture (REDCap), which uses a MySQL database via a secure web 
interface with data checks used during data entry to ensure data quality.  Data 
summaries and quality control checks will be run routinely.  
2. Transparency: All data obtained in this project will be de-identified with each 
study subject receiving a unique study ID number. The de-identified data will be 
routinely shared among team members and discussed at regular meetings to 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 26 of 46 
Template Revised On: 11/1/2021 
evaluate recruitment status and the next step of experiments, analyses, and 
interpretation of the findings. Results of our studies will be submitted for 
publication in peer reviewed journals, and NIH requirements for access of 
manuscripts through PubMed Central will be fulfilled. 
16.0 Health Information and Privacy Compliance 
 
 
16.1 
Select which of the following is applicable to your research: 
☐ My research does not require access to individual health information and 
therefore assert HIPAA does not apply.   
 
X☐ I am requesting that all research participants sign a HIPCO approved HIPAA 
Disclosure Authorization to participate in the research (either the standalone 
form or the combined consent and HIPAA Authorization). 
☐ I am requesting the IRB to approve a Waiver or an alteration of research 
participant authorization to participate in the research. 
☐ An external IRB (e.g. Advarra) is reviewing and we are requesting use of the 
authorization language embedded in the template consent form in lieu of the 
U of M stand-alone HIPAA Authorization.  Note: External IRB must be serving 
as the privacy board for this option. 
 
16.2 
Identify the source of Private Health Information you will be using for your 
research (Check all that apply)   
X☐ I will use the Informatics Consulting Services (ICS) available through CTSI 
(also referred to as the University's Information Exchange (IE) or data 
shelter) to pull records for me 
X☐ I will collect information directly from research participants. 
☐ I will use University services to access and retrieve records from the Bone 
Marrow Transplant (BMPT) database, also known as the HSCT 
(Hematopoietic Stem Cell Transplant) database. 
☐ I will pull records directly from EPIC. 
☐ I will retrieve record directly from axiUm / MiPACS 
☐ I will receive data from the Center for Medicare/Medicaid Services  
☐ I will receive a limited data set from another institution  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 27 of 46 
Template Revised On: 11/1/2021 
☐ Other.  Describe:  
 
16.3 
Explain how you will ensure that only records of patients who have agreed to 
have their information used for research will be reviewed. 
Only patients who have authorized their participation in research in EPIC and have not 
opted out of research will be provided by BPIC for us to review for our study 
recruitment. 
 
16.4 
Approximate number of records required for review: 
Up to 2.8 million (EPIC EHR records). This will be done by BPIC.  Only patients who have 
authorized their participation in research in EPIC will be reviewed. We anticipate that ~ 
2000 records will be referred to us for potential contact for study recruitment. 
16.5 
Please describe how you will communicate with research participants during 
the course of this research.  Check all applicable boxes 
☐ This research involves record review only. There will be no communication 
with research participants. 
☐ Communication with research participants will take place in the course of 
treatment, through MyChart, or other similar forms of communication used 
with patients receiving treatment.  
X☐ Communication with research participants will take place outside of 
treatment settings. If this box is selected, please describe the type of 
communication and how it will be received by participants.  
 
This communication will include the following: 1) phone calls, 2) letters, 3) 
texting and 4) Email. We will communicate with participants via telephone 
(using a study-specific phone number) for pre-screening, appointment 
scheduling, appointment reminders, etc. We will also communicate through 
text message or unsecure email if the participant agrees in writing by signing 
the GUIDELINES AND CONSENT FOR TEXT MESSAGE CORRESPONDENCE FOR 
RESEARCH PARTICIPANTS and/or GUIDELINES AND CONSENT FOR 
UNSECURED EMAIL CORRESPONDENCE FOR RESEARCH PARTICIPANTS. 
16.6 
Explain how the research team has legitimate access to patients/potential 
participants: 
The research team will be permitted to access sources of private information 
because all participants will be required to sign a HIPAA waiver at the time of 
informed consent.  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 28 of 46 
Template Revised On: 11/1/2021 
16.7 Location(s) of storage, sharing and analysis of research data, including any links to 
research data (check all that apply).   
X☐ In the data shelter of the Information Exchange (IE)  
 X☐ Store 
X☐ Analyze 
☐ Share 
☐ In the Bone Marrow Transplant (BMT) database, also known as the HSCT 
(Hematopoietic Stem Cell Transplant) Database  
 ☐ Store 
☐ Analyze 
☐ Share 
X☐ In REDCap (recap.ahc.umn.edu)  
 X☐ Store 
X☐ Analyze 
☐ Share 
☐ In Qualtrics (qualtrics.umn.edu) 
 ☐ Store 
☐ Analyze 
☐ Share 
X☐ In OnCore (oncore.umn.edu)  
 X☐ Store 
X☐ Analyze 
X☐ Share 
X☐ In the University’s Box Secure Storage (box.umn.edu) 
 X☐ Store 
X☐ Analyze 
X☐ Share 
X☐ In an AHC-IS supported server. Provide folder path, location of server and IT 
Support Contact: 
MedDerm(\\med.ahc.umn.edu\med)(N:)\Chow Group  
 X☐ Store 
X☐ Analyze 
X☐ Share 
X☐ In an AHC-IS supported desktop or laptop.  
Provide UMN device numbers of all devices: 20181216 
 X☐ Store 
X☐ Analyze 
X☐ Share 
X☐ Other. Describe:  
Describe in detail the location and whether the data / specimens will be stored, 
analyzed, or shared, and in what ways. 
Indicate if  data will be collected, downloaded, accessed, shared or stored using a 
server, desktop, laptop, external drive or mobile device (including a tablet 
computer such as an iPad or a smartform (iPhone or Android devices) that you 
have not already identified in the preceding questions 
☐I will use a server not previously listed to collect/download research data 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 29 of 46 
Template Revised On: 11/1/2021 
☐I will use a desktop or laptop not previously listed 
☐I will use an external hard drive or USB drive (“flash” or “thumb” drives) not 
previously listed  
X☐I will use a mobile device such as an tablet or smartphone not previously 
listed 
AHC tablet to input survey data (20181716) at each in-person visit 
 
16.8 Consultants. Vendors. Third Parties.  
Electronic data will be shared with our external collaborators using the UMN Box 
account. We will also use the UMN Box account to store results from our external 
collaborators.  All samples sent to the external collaborators (i.e. electronic 
information to Dr. Panda) will be sent de-identified. These samples will be 
analyzed and stored in their laboratories as per their institutional protocol. 
Results from our external collaborators will be placed into the UMN Box account 
(as per above) for our analysis.  
 
16.9 Links to identifiable data: There is be a participant unique study ID established in 
REDCap, which will link participants to the data. This will be used to identify the 
data with the REDCap data.  All shared data will be deidentified.   
 
16.10 Sharing of Data with Research Team Members.  Data between study members 
at the University of Minnesota will be shared by phone, voice mail, U of MN 
email, BOX, centralized shared drive, and REDCap. 
 
16.11 Storage of Documents: In accordance with NIH policy, all study documents will 
be maintained for at least 3 years after the study ends and for a longer time if 
required by University of Minnesota policy. All signed and dated HIPAA 
authorizations and consent documents that include HIPAA authorizations wil be 
maintained for at least 6 years after completion of the study.   
 
16.12 Disposal of Documents: After this time period, all research records will be 
destroyed. Computer files will be deleted and hard copy materials will be 
discarded in accordance with University of Minnesota policy. 
 
17.0 Confidentiality 
17.1 Data Security:  
• Training: All study staff will be appropriately trained in data security. 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 30 of 46 
Template Revised On: 11/1/2021 
• Authorization of access: Only designated IRB-approved staff will have access to 
the data. 
• Password protection/encryption/physical controls: All data will be stored in 
REDCap. 
• Certificates of confidentiality:  Since this study will be funded by an NIH RO1 
Grant, we will apply for a NIH Certificate of Confidentiality. All entities that are 
part of this study will be subject to the requirements of this Certificate. 
• Separation of Identifiers: Study staff will keep the mapping of identification 
code to the identity of the participant in a database protected by two-levels of 
password protection stored separately from the data on Box. 
• A Certificate of Confidentiality is automatically issued by the NIH For this 
project.   
18.0 Provisions to Monitor the Data to Ensure the Safety of Participants 
  
18.1 Data Integrity Monitoring.  
Monitoring will be conducted by study staff and the IRB in accordance with the 
established monitoring plan.  Monitoring events will include the following: Study 
recruitment, subject compliance with visits, subject accrual, adverse events, 
stopping rules with regard to enrollment/drop out/missing data/adverse events.  
The data for each subject will be entered into a REDCap database. The REDCap 
database uses a MySQL database via a secure web interface with data checks 
used during data entry to ensure data quality. REDCap includes a complete suite 
of features to support HIPAA compliance, including a full audit trail, user-based 
privileges, and integration with the institutional LDAP server. The MySQL 
database and the web server will both be housed on secure servers operated by 
the University of Minnesota Academic Health Center’s Information Systems group 
(AHC-IS). The servers are in a physically secure location on campus and are 
backed up nightly, with the backups stored in accordance with the AHC-IS 
retention schedule of daily, weekly, and monthly tapes retained for 1 month, 3 
months, and 6 months, respectively. Weekly backup tapes are stored offsite. The 
AHC-IS servers provide a stable, secure, well-maintained, and high-capacity data 
storage environment, and both REDCap and MySQL are widely-used, powerful, 
reliable, well-supported systems. Access to the study's data in REDCap will be 
restricted to the members of the study team by username and password. 
The clinical data will be reviewed weekly by the study team to ensure progress, 
timely data entry and addressing missing data. The clinical data will also be 
reviewed monthly by Dr. Chow to double-check proper data entry and missing 
data.   

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 31 of 46 
Template Revised On: 11/1/2021 
 
18.2 Data Safety Monitoring.  
Recording of Adverse Event:  
 At each contact with the subject, the investigator and study staff must seek 
information on adverse events by specific questioning and, as appropriate, by 
examination. Information on all adverse events should be recorded immediately 
in the source document, and also in the appropriate adverse event module of the 
case report form (CRF).  All clearly related signs, symptoms, and abnormal 
diagnostic procedures results should be recorded in the source document, though 
should be grouped under one diagnosis. 
 All adverse events occurring during the study period must be recorded. The 
clinical course of each event should be followed until resolution, stabilization, or 
until it has been determined that the study participation is not the cause.  Serious 
adverse events that are still ongoing at the end of the study period must be 
followed up to determine the final outcome.  Any serious adverse event that 
occurs after the study period and is considered to be possibly related to the study 
participation should be recorded and reported immediately. 
Reporting of Serious Adverse Events 
 A serious adverse event is any adverse event that is: 1) Fatal 2) Life Threatening 
3) Requires or prolongs a hospital stay 4) Results in persistent or significant 
disability or incapacity or 5) A congenital anomaly or birth defect. Of note, 
important medical events are events that may not be immediately life-
threatening, but are clearly of major clinical significance and may be a serious 
adverse event. They may jeopardize the subject, and may require intervention to 
prevent one or the other serious outcomes noted above. 
Adverse Event Reporting Plan:  
 Reporting of adverse events will follow University of Minnesota IRB 
requirements. Within 48 hrs of any serious adverse event, a verbal or email 
report will be made to IRB followed by a detailed written report within 10 
business days. 
Patient safety officer: 
 We will have Dr. Amir Moheet serve as the patient safety officer for the study. 
He will review any adverse events related to the study, independent of the IRB 
and the clinical trials monitor. His report will be submitted to the IRB. His focus 
will be to provide independent medical opinion on study associated adverse 
events.   
IRB Notification by Investigators 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 32 of 46 
Template Revised On: 11/1/2021 
 Reports of all serious adverse events (including follow-up information) must be 
submitted to the IRB within 10 working days if it falls under the UPIRTSO 
guidelines.  Copies of each report and documentation of IRB notification and 
receipt will be kept in the Clinical Investigator’s binder 
Unanticipated Problems Involving Risk To Subjects or Others (UPIRTSO) Events 
Investigators are required to submit a report of UPIRTSO events to the IRB within 
10 working days of first learning of the event. 
Responsible Individual(s) or Group 
 Monitoring will be conducted by the PI, IRB and independently (i.e. at least 
annually as a minimum) by qualified staff of the University of Minnesota’s Clinical 
and Translational Science Institute (CTSI, supported by the CTSA grant awarded in 
2018) in accordance with the established monitoring plan.   
19.0 Provisions to Protect the Privacy Interests of Participants 
19.1 Protecting Privacy:  
The study consent form will describe in detail any intrusive, uncomfortable, or 
unfamiliar questions, procedures, or interactions with researchers or study 
personnel that the participant will be asked to complete. Furthermore, the study 
consent form will communicate that it is the participant’s right to opt-out of any 
study procedures or the study as a whole or withdraw from the study at any time 
and this information will be reiterated and revisited periodically throughout the 
study in advance of intrusive, uncomfortable, or unfamiliar questions procedures 
or interactions. Participants will not be compelled or pressured to provide 
information or specimens or study data that they do not wish to provide.    
19.2 Access to Participants: Participants have been fully informed of the ways in which 
their data will/may be used during the informed consent process. The research 
team has been trained in conducting these conversations and the participants are 
also assessed for their understanding of consent prior to signing the consent form 
or initiating any study procedures.   
20.0 Compensation for Research-Related Injury 
20.1 Compensation for Research-Related Injury:  
In the event that research-related activities result in an injury, treatment will be 
provided to the participant (e.g., first aid, emergency treatment, and follow-up 
care as needed). Care for such injuries will be billed in the ordinary manner to the 
participant or the participant’s insurance company.   
20.2 Contract Language: N/A. 
21.0 Consent Process 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 33 of 46 
Template Revised On: 11/1/2021 
21.1 Consent Process (when consent will be obtained):  
Consent forms describing in detail the study, study procedures, and risks are 
given to the participant and documentation of informed consent is required prior 
to any research procedures via written signatures or esignatures using REDCap. 
The following consent materials are submitted with this protocol: 
Consent will take place via a virtual visit using Zoom or Doximity. Participants will 
have the opportunity to carefully review the written consent form and ask 
questions prior to signing. The participants will be given the opportunity to review 
the consent with family and caregivers and return on a subsequent day to sign 
the consent and enroll in the study. 
 Informed consent is a process that is initiated prior to the individual’s agreeing to 
participate in the study and continues throughout the individual’s study 
participation. Extensive discussion of risks and possible benefits of participation 
will be provided to the participants and their families. Consent forms will be IRB-
approved and the participant will be asked to read and review the document. The 
investigator will explain the research study to the participant and answer any 
questions that may arise. We will use the teach-back method to assess the 
participant’s understanding of the study.  
 All participants will receive a verbal explanation in terms suited to their 
comprehension of the purposes, procedures, and potential risks of the study and 
of their rights as research participants. Participants will have the opportunity to 
carefully review the written consent form and ask questions prior to signing. The 
participants should have the opportunity to discuss the study with others or think 
about it prior to agreeing to participate. The participant will sign the informed 
consent document prior to any procedures being done specifically for the study. 
The participants may withdraw consent at any time throughout the course of the 
trial. A copy of the informed consent document will be given to the participants 
for their records. The rights and welfare of the participants will be protected by 
emphasizing to them that the quality of their medical care will not be adversely 
affected if they decline to participate in this study.      
  
21.2 Waiver or Alteration of Consent Process (when consent will not be obtained): 
We will obtain verbal consent over the phone for subject to be fasting for the first 
visit.    
21.3 Waiver of Written/Signed Documentation of Consent (when written/signed 
consent will not be obtained):  
We will ask the IRB to approve a Waiver of Signed Documentation of Consent for 
the phone screening to determine eligibility and to explain to the potential 
participant what will happen during the Virtual Screening Visit.      

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 34 of 46 
Template Revised On: 11/1/2021 
 
21.4 Non-English Speaking Participants:  
N/A 
21.5 Participants Who Are Not Yet Adults (infants, children, teenagers under 18 years 
of age): 
N/A 
21.6 Cognitively Impaired Adults, or adults with fluctuating or diminished capacity to 
consent: 
N/A 
21.7 Adults Unable to Consent: 
N/A 
22.0 Setting 
22.1 Research Sites:  
Fairview Health System Electronic Health Record (EHR):  
The University of Minnesota is a partner of the Fairview Health System which 
uses a modern enterprise level EHR (EPIC) since 2011 As of May 2021, the 
Fairview EHR has 3.3 million living patients, with 19465 research-eligible patients 
with T2DM treated by metformin alone. This constitutes a pool of ~20000 patients 
with T2DM who are eligible for study recruitment. Based on our previous 
experience, we anticipate a 10% response rate to this targeted, recruitment 
approach 
UMMC Central Lab 
Blood work, other than saved serum/ plasma samples, will be processed at the 
UMMC main lab and results faxed to the PI.  
Clinical and Translational Science Institute (CTSI), University of Minnesota 
The Clinical and Translational Science Institute (CTSI) at the University of 
Minnesota offers comprehensive research support for clinical investigators, from 
concept through publication. CTSI supports all stages of the research process, 
providing research and regulatory support, specialized facilities, and analytical 
services. Concept and pre-study services include assistance with study design 
(biostatistical support), protocol and budget development, study population 
definition (i2b2/SHRINE resources), bioinformatics support, investigational new 
drug (IND) or investigational device exemption (IDE) application assistance, 
contract negotiations, institutional committee’s approval assistance (IRB, 
Radiation Safety, Institutional Biosafety, etc.), and clinical trial registration with 
ClinicalTrials.gov. CTSI also offers educational and training opportunities for new 
investigators and study coordinators. Strong relationships across the University’s 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 35 of 46 
Template Revised On: 11/1/2021 
Academic Health Center provide access to extensive expertise and collaborative 
opportunities. Biological specimen handling, storage and retrieval facilities and 
software (caTissue) are available within the University.  
Dr. Chow will be doing most of her clinical research work at the Clinical Research 
Unit (CRU), a 16,250 square foot inpatient facility including 10 inpatient beds, 4 
outpatient beds, rooms dedicated to glucose clamp studies, rooms for human 
performance studies with specialized equipment for exercise testing, non-invasive 
vascular investigation and body composition assessments. The CRU is directly 
connected to the University of Minnesota Medical Center, Fairview and the office 
building (Phillips Wangensteen Building) where Dr. Chow has her office. 
Implementation staffing (research project managers, research nurses and 
certified medical assistants, clinical research coordinators, clinical trial monitors, a 
registered dietitian, laboratory technician, and other specialized technical 
services) can be provided to the extent needed by the investigator. Trial 
monitoring, and ongoing regulatory reporting and support are provided. The CTSI 
provides comprehensive clinical research facilities and support across specialty 
areas, tailored to the needs of the investigator, to facilitate effective and efficient 
use of resources without unnecessary duplication. 
Nutrition Coordinating Center:   
The Nutrition Coordinating Center (NCC) is located in the Division of Epidemiology 
and Community Health, and occupies about 6,000 square feet of office space. Dr. 
Lisa Harnack (Co-I) is the Director of the NCC since 2007. The NCC includes office 
space for staff, telephone calling stations, resource area, training room, and 
conference rooms. The NCC has developed and maintains a research-quality food 
and nutrient database linked to computerized interactive interview software, the 
Nutrition Data System for Research (NDSR). The NDSR is designed primarily for 
clinical research and epidemiological studies investigating relationships between 
diet and health.  The NDSR dietary data collection and nutrient analysis tool is 
well recognized in the nutrition research community and has been licensed for 
use in hundreds of research studies. Clients may also choose to enlist the services 
of NCC to accomplish some or all of their dietary data collection and processing 
objectives. The NCC Service Center offers training and certification of dietary 
interviewers, collection of dietary intake by telephone interview, processing of 
food records, analysis of menu and recipe data, development of dietary data 
collection protocols, and customized support services for additional related 
research needs. The Service Center has provided the aforementioned types of 
services to hundreds of studies since 1974, including carrying out entry and 
nutrient analysis of food records obtained via meal observation procedures 
similar to those to be utilized in the proposed study. 
Salk Institute: 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 36 of 46 
Template Revised On: 11/1/2021 
Environment. The Salk Institute offers an excellent intellectual environment for 
the scientific success of its faculty. Dr. Panda’s lab is part of the Regulatory 
Biology Laboratories and is housed in the same floor as the Laboratory of 
Genetics. The open lab structure of the institute offers constant scientific 
exchange among researchers and PIs. Open lab design of the Salk Institute fosters 
persistent interactions among these lab members. Panda lab has ongoing 
collaborations with several Salk Institute faculty in the field of metabolism, 
endocrinology, and data science. They include Ron Evans, Marc Montminy, 
Reuben Shaw, Saket Navlakha, Alan Saghatelian with whom Panda lab has several 
active collaboration projects. These colleagues and their scientific staffs offer a 
productive intellectual environment relevant to the success of this project. 
 
Laboratory. Laboratory space for 10 full time researchers furnished with standard 
laboratory equipment (thermocyclers, benchtop centrifuges, dissecting 
microscopes, DNA/RNA, protein gel electrophoresis apparatus, heat blocks, water 
baths, freezers, refrigerators, tissue culture hoods, tissue culture incubators, Q-
PCR, FPLC) is available within the department of Regulatory biology at Salk 
institute. 
Clinical. The lab has developed, validated, and deployed the myCircadianClock 
app for monitoring and intervening human eating pattern. The app is hosted on 
secured HIPAA compliant Amazon Web Server (AWS). The database and the 
backend processes communicate with the user’s smartphone using double 
encryption. 
Computer. The laboratory has 12 recent model PCs, and 3 Macintosh computers. 
In addition, shared facilities at Salk include high-end personal computers for 
image processing, database searches, and modeling. Salk institute’s central 
Research Computing department maintains an extensive data communications 
network available to all laboratories. 
Office. The PI has a 100 sq. ft. office located adjacent to the laboratory; desk with 
computer are available for staff associated with the project. 
 
Biostatistical Design & Analysis Center (BDAC) 
Several SPARC servers (Solaris operating system) and Intel servers (Linux and 
FreeBSD operating systems) provide application service to the CCBR and the 
Division of Biostatistics. Access to these applications is provided by more than 100 
thin-client (X-servers) desktops. All servers are connected to the Internet. The 
CCBR machines have more than 20 terabytes of disk storage available. Statistical 
analysis and data management are the primary applications provided by the 
servers. Statistical analyses are performed using SAS, SAS/GRAPH, SAS/IML, and 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 37 of 46 
Template Revised On: 11/1/2021 
R. Oracle is the primary relational database management system. Various SQL 
clients are used including SAS, Perl, SQL*Plus, and PHP. 
22.2 International Research:  
N/A  
 
23.0 Multi-Site Research 
N/A 
24.0 Coordinating Center Research 
 
N/A  
 
25.0 Resources Available 
25.1 Resources Available:  
Division of Endocrinology, Department of Medicine, University of Minnesota 
(Primary location Dr. Lisa Chow, PI, Contact PI) 
Office:  
The Division of Endocrinology has adequate office space for this project. Each 
faculty member has an individual office and computer assigned for their use. 
Modern office equipment such as facsimile machines, photocopiers, postage 
machine, and mailroom services will be available to this project.  
Computer Services: 
The Division of Endocrinology is part of the Academic Health Center (AHC) and 
has AHC support for computer maintenance and centralized backup of computer 
files.  
Clinical and Translational Science Institute (CTSI), University of Minnesota 
The Clinical and Translational Science Institute (CTSI) at the University of 
Minnesota offers comprehensive research support for clinical investigators, from 
concept through publication. CTSI supports all stages of the research process, 
providing research and regulatory support, specialized facilities, and analytical 
services. Concept and pre-study services include assistance with study design 
(biostatistical support), protocol and budget development, study population 
definition (i2b2/SHRINE resources), bioinformatics support, investigational new 
drug (IND) or investigational device exemption (IDE) application assistance, 
contract negotiations, institutional committee’s approval assistance (IRB, 
Radiation Safety, Institutional Biosafety, etc.), and clinical trial registration with 
ClinicalTrials.gov. CTSI also offers educational and training opportunities for new 
investigators and study coordinators. Strong relationships across the University’s 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 38 of 46 
Template Revised On: 11/1/2021 
Academic Health Center provide access to extensive expertise and collaborative 
opportunities. Biological specimen handling, storage and retrieval facilities and 
software (caTissue) are available within the University.  
During the clinical study, both inpatient and outpatient adult clinical spaces are 
available in several facilities. Dr. Chow will be doing most of her clinical research 
work at the Clinical Research Unit (CRU), a 16,250 square foot inpatient facility 
including 10 inpatient beds, 4 outpatient beds, rooms dedicated to glucose clamp 
studies, rooms for human performance studies with specialized equipment for 
exercise testing, non-invasive vascular investigation and body composition 
assessments. The CRU is directly connected to the University of Minnesota 
Medical Center, Fairview and the office building (Phillips Wangensteen Building) 
where Dr. Chow has her office. The Delaware Clinical Research Unit (DCRU), a 
36,750 square foot outpatient facility including separate adult and pediatric 
oriented facilities: Adult facilities include: 10 exam rooms, 4 consultation rooms, 5 
specialized rooms, a metabolic kitchen, sample acquisition room and on-site 
laboratory. The facility provides 23 free parking spaces for research participants.  
Implementation staffing (research project managers, research nurses and 
certified medical assistants, clinical research coordinators, clinical trial monitors, a 
registered dietitian, laboratory technician, and other specialized technical 
services) can be provided to the extent needed by the investigator. A state of the 
art iDXA for bone density and body composition is available on site. Trial 
monitoring, and ongoing regulatory reporting and support are provided. The CTSI 
provides comprehensive clinical research facilities and support across specialty 
areas, tailored to the needs of the investigator, to facilitate effective and efficient 
use of resources without unnecessary duplication. 
Data for this study will be entered into a REDCap database. The REDCap database 
uses a MySQL database via a secure web interface with data checks used during 
data entry to ensure data quality. REDCap includes a complete suite of features to 
support HIPAA compliance, including a full audit trail, user-based privileges, and 
integration with the institutional LDAP server. The MySQL database and the web 
server will both be housed on secure servers operated by the University of 
Minnesota Academic Health Center’s Information Systems group (AHC-IS). The 
servers are in a physically secure location on campus and are backed up nightly, 
with the backups stored in accordance with the AHC-IS retention schedule of 
daily, weekly, and monthly tapes retained for 1 month, 3 months, and 6 months, 
respectively. Weekly backup tapes are stored offsite. The AHC-IS servers provide 
a stable, secure, well- maintained, and high-capacity data storage environment, 
and both REDCap and MySQL are widely-used, powerful, reliable, well-supported 
systems. Access to the study's data in REDCap will be restricted to the members 
of the study team by username and password. 
Fairview Health System Electronic Health Record (EHR):  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 39 of 46 
Template Revised On: 11/1/2021 
The University of Minnesota is a partner of the Fairview Health System which 
uses a modern enterprise level EHR (EPIC) since 2011. As of May 2021, the 
Fairview EPIC system has 3.3 million living patients, with 19465 research-eligible 
patients with T2DM treated by metformin alone. This constitutes a pool of 
~20000 patients with T2DM who are eligible for study recruitment. Based on our 
previous experience, we anticipate a 10% response rate to this targeted, 
recruitment approach.  
Division of Epidemiology and Community Health, School of Public Health, 
University of Minnesota 
(Primary location Dr. Lisa Harnack, Co-I) 
Nutrition Coordinating Center:   
The Nutrition Coordinating Center (NCC) is located in the Division of Epidemiology 
and Community Health, and occupies about 6,000 square feet of office space. Dr. 
Lisa Harnack (Co-I) is the Director of the NCC since 2007. The NCC includes office 
space for staff, telephone calling stations, resource area, training room, and 
conference rooms. The NCC has developed and maintains a research-quality food 
and nutrient database linked to computerized interactive interview software, the 
Nutrition Data System for Research (NDSR). The NDSR is designed primarily for 
clinical research and epidemiological studies investigating relationships between 
diet and health.  The NDSR dietary data collection and nutrient analysis tool is 
well recognized in the nutrition research community and has been licensed for 
use in hundreds of research studies. Clients may also choose to enlist the services 
of NCC to accomplish some or all of their dietary data collection and processing 
objectives. The NCC Service Center offers training and certification of dietary 
interviewers, collection of dietary intake by telephone interview, processing of 
food records, analysis of menu and recipe data, development of dietary data 
collection protocols, and customized support services for additional related 
research needs. The Service Center has provided the aforementioned types of 
services to hundreds of studies since 1974, including carrying out entry and 
nutrient analysis of food records obtained via meal observation procedures 
similar to those to be utilized in the proposed study. 
The Nutrition Coordinating Center was established in 1974, and continues to 
address the ongoing needs of the nutrition research community. The Center is 
located on West Bank of the University of Minnesota campus and is a 10 minute 
drive from Dr. Chow’s office. 
 
26.0 References 
 
1. 
Gabel K, Hoddy KK, Haggerty N, Song J, Kroeger CM, Trepanowski JF, Panda S, 
Varady KA. Effects of 8-hour time restricted feeding on body weight and metabolic disease risk 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 40 of 46 
Template Revised On: 11/1/2021 
factors in obese adults: A pilot study. Nutrition and healthy aging. 2018;4(4):345-53. PubMed 
PMID: 29951594. 
2. 
Wilkinson MJ, Manoogian ENC, Zadourian A, Lo H, Fakhouri S, Shoghi A, Wang X, 
Fleischer JG, Navlakha S, Panda S, Taub PR. Ten-Hour Time-Restricted Eating Reduces 
Weight, Blood Pressure, and Atherogenic Lipids in Patients with Metabolic Syndrome. Cell 
Metabolism. 2020;31(1):92-104.e5; PMCID: PMID: 31813824 PMCID: PMC6953486  
3. 
Strelitz J, Ahern AL, Long GH, Hare MJL, Irving G, Boothby CE, Wareham NJ, Griffin 
SJ. Moderate weight change following diabetes diagnosis and 10 year incidence of 
cardiovascular disease and mortality. Diabetologia. 2019;62(8):1391-402. PubMed PMID: 
PMID: 31062041 PMCID: PMC6647260. 
4. 
Terranova CO, Brakenridge CL, Lawler SP, Eakin EG, Reeves MM. Effectiveness of 
lifestyle-based weight loss interventions for adults with type 2 diabetes: a systematic review and 
meta-analysis. Diabetes Obesity & Metabolism. 2015;17(4):371-8. PubMed PMID: PMID: 
25523815. 
5. 
LeBlanc ES, Patnode CD, Webber EM, Redmond N, Rushkin M, O’Connor EA. 
Behavioral and Pharmacotherapy Weight Loss Interventions to Prevent Obesity-Related 
Morbidity and Mortality in Adults: Updated Evidence Report and Systematic Review for the 
US Preventive Services Task Force. JAMA. 2018;320(11):1172-91; PMCID: PMID: 30326501  
6. 
Vijan S, Stuart NS, Fitzgerald JT, Ronis DL, Hayward RA, Slater S, Hofer TP. Barriers 
to following dietary recommendations in Type 2 diabetes. Diabetic medicine : a journal of the 
British Diabetic Association. 2005;22(1):32-8. PubMed PMID: 15606688. 
7. 
Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CM. Early Time-
Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even 
without Weight Loss in Men with Prediabetes. Cell Metabolism. 2018;27(6):1212-+; PMCID: 
PMID: 29754952 PMCID: PMC5990470  
8. 
Chow LS, Manoogian ENC, Alvear A, Fleischer JG, Thor H, Dietsche K, Wang Q, 
Hodges JS, Esch N, Malaeb S, Harindhanavudhi T, Nair KS, Panda S, Mashek DG. Time-
Restricted Eating Effects on Body Composition and Metabolic Measures in Humans who are 
Overweight: A Feasibility Study. Obesity (Silver Spring, Md). 2020;28(5):860-9. PubMed 
PMID: 32270927; PMCID: PMC7180107. 
9. 
Crose A, Alvear A, Singroy S, Wang Q, Manoogian E, Panda S, Mashek DG, Chow LS. 
Time-Restricted Eating Improves Quality of Life Measures in Overweight Humans. Nutrients. 
2021;13(5):1430. PubMed PMID: doi:10.3390/nu13051430; PMCID: PMID: 33922683 
PMCID: PMC8146708. 
10. 
Gill S, Panda S. A Smartphone App Reveals Erratic Diurnal Eating Patterns in Humans 
that Can Be Modulated for Health Benefits. Cell Metabolism. 2015;22(5):789-98; PMCID: 
PMID: 26411343 PMCID: PMC4635036  
11. 
UKPDS. Intensive blood-glucose control with sulphonylureas or insulin compared with 
conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). 
Lancet. 1998;352(9131):837-53. PubMed PMID: 9742976. 
12. 
ACCORD. Effects of Medical Therapies on Retinopathy Progression in Type 2 
Diabetes. The New England journal of medicine. 2010;363(3):233-44. PubMed PMID: 
PMC4026164. 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 41 of 46 
Template Revised On: 11/1/2021 
13. 
ADVANCE. Intensive blood glucose control and vascular outcomes in patients with 
type 2 diabetes. New England Journal of Medicine. 2008;358(24):2560-72. PubMed PMID: 
18539916. 
14. 
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of 
intensive glucose control in type 2 diabetes. New England Journal of Medicine. 
2008;359(15):1577-89. PubMed PMID: 18784090. 
15. 
CDC. 2020. Available from: https://www.cdc.gov/diabetes/pdfs/data/statistics/national-
diabetes-statistics-report.pdf. 
16. 
Zhou X, Shrestha SS, Shao H, Zhang P. Factors Contributing to the Rising National 
Cost of Glucose-Lowering Medicines for Diabetes During 2005–2007 and 2015–2017. Diabetes 
Care. 2020;43(10):2396; PMCID: PMID: 32737138 PMCID: PMC7510041. 
17. 
Ockene IS, Tellez TL, Rosal MC, Reed GW, Mordes J, Merriam PA, Olendzki BC, 
Handelman G, Nicolosi R, Ma Y. Outcomes of a Latino community-based intervention for the 
prevention of diabetes: the Lawrence Latino Diabetes Prevention Project. Am J Public Health. 
2012;102(2):336-42. PubMed PMID: 22390448; PMCID: PMC3483988. 
18. 
Rosas LG, Thiyagarajan S, Goldstein BA, Drieling RL, Romero PP, Ma J, Yank V, 
Stafford RS. The effectiveness of two community-based weight loss strategies among obese, 
low-income US Latinos. J Acad Nutr Diet. 2015;115(4):537-50.e2. PubMed PMID: 25578925; 
PMCID: PMC4380577. 
19. 
O'Brien MJ, Perez A, Scanlan AB, Alos VA, Whitaker RC, Foster GD, Ackermann RT, 
Ciolino JD, Homko C. PREVENT-DM Comparative Effectiveness Trial of Lifestyle 
Intervention and Metformin. Am J Prev Med. 2017;52(6):788-97. PubMed PMID: 28237635; 
PMCID: PMC5438762. 
20. 
Wing RR, Lang W, Wadden TA, Safford M, Knowler WC, Bertoni AG, Hill JO, 
Brancati FL, Peters A, Wagenknecht L, Look ARG. Benefits of modest weight loss in 
improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. 
Diabetes care. 2011;34(7):1481-6. PubMed PMID: 21593294. 
21. 
DPP. The Diabetes Prevention Program (DPP): description of lifestyle intervention. 
Diabetes care. 2002;25(12):2165-71. PubMed PMID: 12453955. 
22. 
Knowler WC, Fowler SE, Hamman RF, Christophi CA, Hoffman HJ, Brenneman AT, 
Brown-Friday JO, Goldberg R, Venditti E, Nathan DM. 10-year follow-up of diabetes incidence 
and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 
2009;374(9702):1677-86. PubMed PMID: 19878986; PMCID: PMC3135022. 
23. 
Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, 
Nathan DM, Diabetes Prevention Program Res G. Reduction in the incidence of type 2 diabetes 
with lifestyle intervention or metformin. New England Journal of Medicine. 2002;346(6):393-
403. PubMed PMID: PMID: 11832527 PMCID: PMC1370926. 
24. 
Wadden TA, West DS, Delahanty L, Jakicic J, Rejeski J, Williamson D, Berkowitz RI, 
Kelley DE, Tomchee C, Hill JO, Kumanyika S. The Look AHEAD study: a description of the 
lifestyle intervention and the evidence supporting it. Obesity (Silver Spring, Md). 
2006;14(5):737-52. PubMed PMID: 16855180; PMCID: PMC2613279. 
25. 
Kraschnewski JL, Sciamanna CN, Stuckey HL, Chuang CH, Lehman EB, Hwang KO, 
Sherwood LL, Nembhard HB. A silent response to the obesity epidemic: decline in US 
physician weight counseling. Med Care. 2013;51(2):186-92. PubMed PMID: 23047128. 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 42 of 46 
Template Revised On: 11/1/2021 
26. 
Rushing J, Wing R, Wadden TA, Knowler WC, Lawlor M, Evans M, Killean T, Montez 
M, Espeland MA, Zhang P, Look ARG. Cost of intervention delivery in a lifestyle weight loss 
trial in type 2 diabetes: results from the Look AHEAD clinical trial. Obes Sci Pract. 
2017;3(1):15-24. PubMed PMID: 28392928. 
27. 
Lowe DA, Wu N, Rohdin-Bibby L, Moore AH, Kelly N, Liu YE, Philip E, Vittinghoff 
E, Heymsfield SB, Olgin JE, Shepherd JA, Weiss EJ. Effects of Time-Restricted Eating on 
Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and 
Obesity: The TREAT Randomized Clinical Trial. JAMA Internal Medicine. 2020; PMCID: 
PMID: 32986097 PMCID: PMC7522780. 
28. 
Hutchison AT, Regmi P, Manoogian ENC, Fleischer JG, Wittert GA, Panda S, 
Heilbronn LK. Time-Restricted Feeding Improves Glucose Tolerance in Men at Risk for Type 2 
Diabetes: A Randomized Crossover Trial. Obesity. 2019;27(5):724-32; PMCID: PMID: 
31002478. 
29. 
Parr EB, Devlin BL, Radford BE, Hawley JA. A Delayed Morning and Earlier Evening 
Time-Restricted Feeding Protocol for Improving Glycemic Control and Dietary Adherence in 
Men with Overweight/Obesity: A Randomized Controlled Trial. Nutrients. 2020;12(2). PubMed 
PMID: 32079327; PMCID: PMC7071240. 
30. 
Lalia AZ, Dasari S, Johnson ML, Robinson MM, Konopka AR, Distelmaier K, Port JD, 
Glavin MT, Esponda RR, Nair KS, Lanza IR. Predictors of Whole-Body Insulin Sensitivity 
Across Ages and Adiposity in Adult Humans. The Journal of Clinical Endocrinology & 
Metabolism. 2016;101(2):626-34. PubMed PMID: 26709968. 
31. 
Bantle AE, Bosch TA, Dengel DR, Wang Q, Mashek DG, Chow LS. DXA-Determined 
Regional Adiposity Relates to Insulin Resistance in a Young Adult Population with Overweight 
and Obesity. Journal of Clinical Densitometry. 2019;22(2):287-92; PMCID: PMID: 30064815 
PMCID: PMC6391218. 
32. 
Arnason TG, Bowen MW, Mansell KD. Effects of intermittent fasting on health markers 
in those with type 2 diabetes: A pilot study. World journal of diabetes. 2017;8(4):154-64; 
PMCID: PMID: 28465792 PMCID: PMC5394735. 
33. 
Jakubowicz D, Landau Z, Tsameret S, Wainstein J, Raz I, Ahren B, Chapnik N, Barnea 
M, Ganz T, Menaged M, Mor N, Bar-Dayan Y, Froy O. Reduction in Glycated Hemoglobin and 
Daily Insulin Dose Alongside Circadian Clock Upregulation in Patients With Type 2 Diabetes 
Consuming a Three-Meal Diet: A Randomized Clinical Trial. Diabetes Care. 2019;42(12):2171-
80. PubMed PMID: 31548244. 
34. 
Kahleova H, Belinova L, Malinska H, Oliyarnyk O, Trnovska J, Skop V, Kazdova L, 
Dezortova M, Hajek M, Tura A, Hill M, Pelikanova T. Eating two larger meals a day (breakfast 
and lunch) is more effective than six smaller meals in a reduced-energy regimen for patients 
with type 2 diabetes: a randomised crossover study. Diabetologia. 2014;57(8):1552-60. PubMed 
PMID: PMID: 24838678 PMCID: PMC4079942. 
35. 
Center PR. Mobile Fact Sheet 2019 [updated June 12, 2019; cited 2019]. Available 
from: http://www.pewinternet.org/fact-sheet/mobile/. 
36. 
Pellegrini CA, Verba SD, Otto AD, Helsel DL, Davis KK, Jakicic JM. The Comparison 
of a Technology-Based System and an In-Person Behavioral Weight Loss Intervention. Obesity. 
2012;20(2):356-63; PMCID: PMID: 21311506 PMCID: PMC3753800. 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 43 of 46 
Template Revised On: 11/1/2021 
37. 
Boushey CJ, Spoden M, Zhu FM, Delp EJ, Kerr DA. New mobile methods for dietary 
assessment: review of image-assisted and image-based dietary assessment methods. The 
Proceedings of the Nutrition Society. 2017;76(3):283-94. PubMed PMID: 27938425. 
38. 
Maguen S, Hebenstreit C, Li Y, Dinh JV, Donalson R, Dalton S, Rubin E, Masheb R. 
Screen for Disordered Eating: Improving the accuracy of eating disorder screening in primary 
care. General Hospital Psychiatry. 2018;50:20-5; PMCID: PMID: 28987918. 
39. 
Little RJ, D'Agostino R, Cohen ML, Dickersin K, Emerson SS, Farrar JT, Frangakis C, 
Hogan JW, Molenberghs G, Murphy SA, Neaton JD, Rotnitzky A, Scharfstein D, Shih WJ, 
Siegel JP, Stern H. The Prevention and Treatment of Missing Data in Clinical Trials. New 
England Journal of Medicine. 2012;367(14):1355-60. PubMed PMID: 23034025. 
40. 
Malaeb S, Harindhanavudhi T, Dietsche K, Esch N, Manoogian ENC, Panda S, Mashek 
D, Wang Q, Chow LS. Time-Restricted Eating Alters Food Intake Patterns, as Prospectively 
Documented by a Smartphone Application. Nutrients. 2020;12(11). PubMed PMID: 33167321. 
41. 
Matthews CE, Keadle SK, Troiano RP, Kahle L, Koster A, Brychta R, Van Domelen D, 
Caserotti P, Chen KY, Harris TB, Berrigan D. Accelerometer-measured dose-response for 
physical activity, sedentary time, and mortality in US adults. The American journal of clinical 
nutrition. 2016;104(5):1424-32. PubMed PMID: 27707702; PMCID: PMC5081718. 
42. 
Trost SG, Loprinzi PD, Moore R, Pfeiffer KA. Comparison of Accelerometer Cut Points 
for Predicting Activity Intensity in Youth. Medicine and Science in Sports and Exercise. 
2011;43(7):1360-8. PubMed PMID: PMID: 21131873  
43. 
Healy GN, Matthews CE, Dunstan DW, Winkler EAH, Owen N. Sedentary time and 
cardio-metabolic biomarkers in US adults: NHANES 2003-06. Eur Heart J. 2011;32(5):590-7; 
PMCID: PMID: 21224291 PMCID: PMC3634159  
44. 
Tucker JM, Welk GJ, Beyler NK. Physical Activity in US Adults Compliance with the 
Physical Activity Guidelines for Americans. American Journal of Preventive Medicine. 
2011;40(4):454-61; PMCID: PMID: 21406280  
45. 
Sadeh A, Sharkey KM, Carskadon MA. Activity-based sleep-wake identification: an 
empirical test of methodological issues. Sleep. 1994;17(3):201-7. PubMed PMID: PMID: 
7939118  
46. 
Sadeh A, Hauri PJ, Kripke DF, Lavie P. The role of actigraphy in the evaluation of sleep 
disorders. Sleep. 1995;18(4):288-302. PubMed PMID: PMID: 7618029  
47. 
Cole RJ, Kripke DF, Gruen W, Mullaney DJ, Gillin JC. Automatic sleep/wake 
identification from wrist activity. Sleep. 1992;15(5):461-9. PubMed PMID: PMID: 1455130  
48. 
Tate DF, Jeffery RW, Sherwood NE, Wing RR. Long-term weight losses associated 
with prescription of higher physical activity goals. Are higher levels of physical activity 
protective against weight regain? The American journal of clinical nutrition. 2007;85(4):954-9. 
PubMed PMID: 17413092. 
49. 
Jeffery RW, Wing RR, Sherwood NE, Tate DF. Physical activity and weight loss: does 
prescribing higher physical activity goals improve outcome? The American journal of clinical 
nutrition. 2003;78(4):684-9. PubMed PMID: 14522725. 
50. 
Das SK, Roberts SB, Bhapkar MV, Villareal DT, Fontana L, Martin CK, Racette SB, 
Fuss PJ, Kraus WE, Wong WW, Saltzman E, Pieper CF, Fielding RA, Schwartz AV, Ravussin 
E, Redman LM, Group ftC-S. Body-composition changes in the Comprehensive Assessment of 
Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: a 2-y randomized 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 44 of 46 
Template Revised On: 11/1/2021 
controlled trial of calorie restriction in nonobese humans. The American journal of clinical 
nutrition. 2017;105(4):913-27; PMCID: PMID: 28228420 PMCID: PMC5366044  
51. 
Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong EA, Gill S, Leblanc M, 
Chaix A, Joens M, Fitzpatrick JA, Ellisman MH, Panda S. Time-restricted feeding without 
reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 
2012;15(6):848-60. PubMed PMID: 22608008; PMCID: PMC3491655. 
52. 
Chaix A, Zarrinpar A, Miu P, Panda S. Time-Restricted Feeding Is a Preventative and 
Therapeutic Intervention against Diverse Nutritional Challenges. Cell Metabolism. 
2014;20(6):991-1005; PMCID: PMID: 25470547 PMCID: PMC4255155  
53. 
Longo VD, Panda S. Fasting, Circadian Rhythms, and Time-Restricted Feeding in 
Healthy Lifespan. Cell Metabolism. 2016;23(6):1048-59; PMCID: PMID: 27304506 PMCID: 
PMC5388543  
54. 
Versteeg RI, Ackermans MT, Nederveen AJ, Fliers E, Serlie MJ, la Fleur SE. Meal 
timing effects on insulin sensitivity and intrahepatic triglycerides during weight loss. 
International journal of obesity (2005). 2018;42(2):156-62. PubMed PMID: 28811653. 
55. 
Chaix A, Lin T, Le HD, Chang MW, Panda S. Time-Restricted Feeding Prevents 
Obesity and Metabolic Syndrome in Mice Lacking a Circadian Clock. Cell Metab. 
2019;29(2):303-19.e4. PubMed PMID: 30174302. 
56. 
Wing RR. Physical activity in the treatment of the adulthood overweight and obesity: 
current evidence and research issues. Med Sci Sports Exerc. 1999;31(11):S547-S52; PMCID: 
PMID:10593526  
57. 
Bonora E, Saggiani F, Targher G, Zenere MB, Alberiche M, Monauni T, Bonadonna 
RC, Muggeo M. Homeostasis model assessment closely mirrors the glucose clamp technique in 
the assessment of insulin sensitivity - Studies in subjects with various degrees of glucose 
tolerance and insulin sensitivity. Diabetes Care. 2000;23(1):57-63. PubMed PMID: PMID: 
10857969. 
58. 
Levy JC, Matthews DR, Hermans MP. Correct Homeostasis Model Assessment 
(HOMA) Evaluation Uses the Computer Program. Diabetes Care. 1998;21(12):2191; PMCID: 
PMID: 9839117. 
59. 
Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes 
Care. 2004;27(6):1487-95. PubMed PMID: 15161807. 
60. 
Akintola AA, Noordam R, Jansen SW, de Craen AJ, Ballieux BE, Cobbaert CM, 
Mooijaart SP, Pijl H, Westendorp RG, van Heemst D. Accuracy of Continuous Glucose 
Monitoring Measurements in Normo-Glycemic Individuals. PLOS ONE. 
2015;10(10):e0139973; PMCID: PMCID: PMC4596806. 
61. 
Monnier L, Colette C, Wojtusciszyn A, Dejager S, Renard E, Molinari N, Owens DR. 
Toward Defining the Threshold Between Low and High Glucose Variability in Diabetes. 
Diabetes Care. 2016. PubMed PMID: 28039172. 
62. 
Baghurst PA. Calculating the mean amplitude of glycemic excursion from continuous 
glucose monitoring data: an automated algorithm. Diabetes Technol Ther. 2011;13(3):296-302. 
PubMed PMID: 21291334. 
63. 
Monnier L, Colette C, Owens DR. The application of simple metrics in the assessment 
of glycaemic variability. Diabetes Metab. 2018;44(4):313-9. PubMed PMID: 29602622. 
64. 
Brown SA, Basu A, Kovatchev BP. Beyond HbA(1c) : using continuous glucose 
monitoring metrics to enhance interpretation of treatment effect and improve clinical decision-

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 45 of 46 
Template Revised On: 11/1/2021 
making. Diabetic medicine : a journal of the British Diabetic Association. 2019;36(6):679-87. 
PubMed PMID: 30848545. 
65. 
Battelino T, Danne T, Bergenstal RM, Amiel SA, Beck R, Biester T, Bosi E, 
Buckingham BA, Cefalu WT, Close KL, Cobelli C, Dassau E, DeVries JH, Donaghue KC, 
Dovc K, Doyle FJ, 3rd, Garg S, Grunberger G, Heller S, Heinemann L, Hirsch IB, Hovorka R, 
Jia W, Kordonouri O, Kovatchev B, Kowalski A, Laffel L, Levine B, Mayorov A, Mathieu C, 
Murphy HR, Nimri R, Nørgaard K, Parkin CG, Renard E, Rodbard D, Saboo B, Schatz D, 
Stoner K, Urakami T, Weinzimer SA, Phillip M. Clinical Targets for Continuous Glucose 
Monitoring Data Interpretation: Recommendations From the International Consensus on Time 
in Range. Diabetes Care. 2019;42(8):1593-603. PubMed PMID: 31177185; PMCID: 
PMC6973648. 
66. 
Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma 
glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients - Variations 
with increasing levels of HbA(1c). Diabetes Care. 2003;26(3):881-5. PubMed PMID: PMID: 
12610053. 
67. 
Ross KM, Wing RR. Concordance of in-home 'smart' scale measurement with body 
weight measured in-person. Obes Sci Pract. 2016;2(2):224-8; PMCID: PMID: 27499884 
PMCID: PMC4970749  
68. 
Ross KM, Eastman A, Wing RR. Accuracy of Self-Report Versus Objective Smart-
Scale Weights During a 12-Week Weight Management Intervention. Obesity. 2019;27(3):385-
90; PMCID: PMID: 30703282 PMCID: PMC6410568  
69. 
Pebley K, Klesges RC, Talcott GW, Kocak M, Krukowski RA. Measurement 
Equivalence of E-Scale and In-Person Clinic Weights. Obesity. 2019;27(7):1107-14; PMCID: 
PMID: 31168928  
70. 
BodyTrace I. Accessed April 21, 2020. Available from: Frequently asked questions. 
http://www.bodytrace.com/medical/faq.html. . 
71. 
Feskanich D, Sielaff BH, Chong K, Buzzard IM. Computerized collection and analysis 
of dietary intake information. Computer Methods and Programs in Biomedicine. 1989;30(1):47-
57. PubMed PMID: PMID: 2582746. 
72. 
Johnson RK, Driscoll P, Goran MI. Comparison of multiple-pass 24-hour recall 
estimates of energy intake with total energy expenditure determined by the doubly labeled water 
method in young children. J Am Diet Assoc. 1996;96(11):1140-4. PubMed PMID: 8906138. 
73. 
Kirkpatrick SI, Reedy J, Krebs-Smith SM, Pannucci TE, Subar AF, Wilson MM, 
Lerman JL, Tooze JA. Applications of the Healthy Eating Index for Surveillance, 
Epidemiology, and Intervention Research: Considerations and Caveats. Journal of the Academy 
of Nutrition and Dietetics. 2018;118(9):1603-21. PubMed PMID: 30146072. 
74. 
Troiano RP, Berrigan D, Dodd KW, Masse LC, Tilert T, McDowell M. Physical activity 
in the United States measured by accelerometer. Medicine and Science in Sports and Exercise. 
2008;40(1):181-8. PubMed PMID: PMID: 18091006. 
75. 
Lee PH, Suen LK. The convergent validity of Actiwatch 2 and ActiGraph Link 
accelerometers in measuring total sleeping period, wake after sleep onset, and sleep efficiency 
in free-living condition. Sleep Breath. 2017;21(1):209-15. PubMed PMID: 27614441. 
76. 
Baranowski T. 24-Hour Dietary Recall and Diet Record Methods. In Nutritional 
Epidemiology 3rd edition. 2013(Edited by Willett W. New York: Oxford;). 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Time Restricted Eating As a Viable Alternative to Caloric Restriction 
for Treating Hyperglycemia in a Population with Type 2 (T2DM) diabetes 
 
VERSION DATE: 2025.03.26 
 
Page 46 of 46 
Template Revised On: 11/1/2021 
77. 
Harnack L, Pereira M. Strategies for Improving the Validity of the 24-hour Dietary 
Recall and Food Record Methods.  Advances in the Assessment of Dietary Intake: CRC Press; 
2017. p. 67-84. 
78. 
Conway JM, Ingwersen LA, Vinyard BT, Moshfegh AJ. Effectiveness of the US 
Department of Agriculture 5-step multiple-pass method in assessing food intake in obese and 
nonobese women. The American journal of clinical nutrition. 2003;77(5):1171-8. PubMed 
PMID: 12716668. 
79. 
Ware JE, Jr. SF-36 health survey update. Spine (Phila Pa 1976). 2000;25(24):3130-9. 
PubMed PMID: 11124729; PMCID: PMID: 11124729. 
80. 
Flint A, Raben A, Blundell JE, Astrup A. Reproducibility, power and validity of visual 
analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat 
Metab Disord. 2000;24(1):38-48. PubMed PMID: 10702749.