Influence of Time-restricted Eating (TRE) on Circadian Regulation of Glucose Homeostasis and Mitochondrial Function - The TIMET Study
Phase: NA
Conditions: Metabolic Syndrome, Pre-Diabetes
Sponsor: University of California, San Diego

Influence of time-restricted eating (TRE) on circadian 
regulation of glucose homeostasis and mitochondrial 
function — The TIMET Study 
NCT04057339 
DECEMBER 2, 2021 

IRB 181088 
 
1 
 
 
University of California, San Diego 
Consent to Act as a Research Subject 
 
Influence of time-restricted eating (TRE) on circadian regulation of glucose homeostasis and 
mitochondrial function—The TIMET Study 
 
Who is conducting the study, why you have been asked to participate, how you were selected, and 
what is the approximate number of participants in the study? 
Dr. Pam Taub, M.D. is conducting a research study in collaboration with the Dr. Satchidananda 
Panda, PhD at the Salk Institute to measure the health impact of a dietary intervention known as 
time restricted eating (TRE) on patients with metabolic syndrome. You have been asked to 
participate in this study because you are age 18 years or older, you have been identified as having 
metabolic syndrome, and you have reported that you eat over a period of 12 hours or more. 
 
There will be up to 144 participants at this site; this is the only site participating in the study. Up to 
72 participants will be randomly assigned to the standard of care (SOC) group, which will receive 
standard health and nutritional wellness guidelines. Up to 72 participants will be randomly assigned 
to the Time-Restricted Eating (TRE) group which will be asked to limit the number of hours they 
eat in a day to 10 hours in addition to receiving the standard of care health and nutritional wellness 
guidelines. Randomly assigned means that you nor the study team has control over which group 
you are placed into. Your chances for being placed in either group is like flipping a coin; there is a 
50/50 chance of being placed into either the SOC or the TRE group.  
 
All the clinical testing will be performed at the UCSD Altman Clinical and Translational Research 
Institute (ACTRI, 9452 Medical Center Drive, La Jolla CA 92037). 
 
The study is being funded by the National Institutes of Health (NIH).  
 
Why is this study being done? 
The purpose of this study is to see if reducing the number of hours during which you eat each day 
will help reduce your levels of glucose (sugar) in the blood, improve other markers of metabolic 
and cardiovascular health (i.e. lipid levels, inflammation markers, etc), and improve body 
composition (i.e. percentage of body fat, waist circumference, abdominal fat, etc).  
 
Circadian clocks (“circa” means approximately and “dian” means day) are daily rhythms in 
physiology and behavior (activity, sleep, eating pattern) that help our body to anticipate and adapt 
to predictable events in the environment. These rhythms are generated and maintained by 
biological clocks that are present in the brain and in almost every organ of our body. Remarkably, 
even in the absence of any real clock or timing information from a device, our body can keep 
track of time and thereby help us go to sleep and eat at optimum times. However, as we can choose 
to eat, exercise, and go to sleep at a time that is dictated by our lifestyle, sometimes we do these 
daily routines at a time of the day when our body clock has not prepared our body for it. When 
these abnormal daily patterns continue for several weeks or years, it can affect our health in many 
ways including body weight, sleep and risk for various chronic diseases. These daily patterns are 
affected by where we live (such as near to the equator vs in high latitudes where winter days are 
very short), season, our work habits, age and many unknown factors. Particularly, we are interested 
in evaluating the effect of eating patterns on the circadian clock and health.  If you enroll in this 
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
 
2 
 
study and are randomized to the TRE group, you will be asked to choose an 8-10-hour time frame 
for your eating window, meaning you will fast for the remaining 14-16 hours of the day. If you 
have a baseline eating window of 14 hours or more, your eating window for TRE intervention 
will be 10 hours. If you have an eating window of 12-14 hours at baseline, your eating window 
during the TRE intervention will be 4 hours shorter than your baseline. For example, if your 
baseline eating window is 12 hours, the TRE intervention will be 8 hours of eating and 16 
hours of fasting. Eight hours is the shortest eating window and ten hours is the longest eating 
window that those in the TRE group will adopt. The research coordinator will help you select 
the window if you are in this group.   
 
What will happen to you in this study and which procedures are standard of care and which are 
experimental? 
At the beginning and end of the study,  we will measure your height, weight, body mass index, 
percent body fat, waist/hip circumference and blood pressure. We will also measure your blood 
sugar levels continuously for 2 weeks at a time at the beginning and end of the study.  We will do 
this using a continuous glucose monitor which is a device that will be implanted (it will stick onto 
the skin’s surface with a small sensor that will go into the skin).  Additionally, we will use a special 
type of X-ray (Dual energy X-Ray Absorptiometry (DXA)) scan to collect information about your 
body composition (amount of fat compared to muscle and bones). We will also collect information 
about the mitochondria (produces energy for cells in the body) with a muscle biopsy. During the 
study, we will also ask you to use a smartphone application (called myCircadianClock (mCC), 
developed by the Salk Institute) to keep track of what you eat, and a wrist-worn actigraphy device 
(similar to a standard wristwatch) which will monitor your physical activity levels and sleep.  By 
consenting to this study, you are also consenting to use mCC app and also allowing the mCC 
app/Salk research team to share data with our team at UCSD. 
 
During the study, you will be asked not to adjust the dosage of or start certain types of medications, 
specifically those affecting blood pressure, cholesterol, and blood sugar, unless recommended by 
your doctor. If such a change occurs, we ask that you inform us of the change as soon as possible. 
 
All of the following procedures are experimental. If you enroll in this study, the following will take 
place as part of the study. 
A. Visit 1: You will be asked to come to the ACTRI in La Jolla in a fasting state for initial 
assessment and blood work.   
a. We will measure your height, weight, body mass index, waist and hip 
circumference, and resting blood pressure.   
b. We will also obtain blood tests by standard vein puncture with a needle.  
c. You will be implanted a continuous glucose monitor on one of your upper arms, and 
you will be fitted with the wrist-worn actigraphy device (similar to a wrist-worn 
watch). You will wear both for 2 weeks.  
1. This step will not take place if your labs are not recent enough for us 
to determine your eligibility for the study. In this case, all other 
procedures will occur at this visit, but the watch and CGM will not be 
applied until your lab results have been reviewed and confirm your 
eligibility. Then, you will be asked to return to the ACTRI for the 
watch and CGM and your baseline period will begin at this time. 
d. You will then be provided with instructions for installing and using a smartphone 
application which you will use during the study to record your dietary intake.   
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
 
3 
 
e. You will also be asked to complete general health and sleep questionnaires.  
f. This visit will take 1-1.5 hours.  
g. You will receive $50 for this visit. 
B. Visit 2: You will be asked to come to the ACTRI in a fasted state for a muscle biopsy and 
DXA scan.  
a. You will be asked to undergo a muscle biopsy on one of your thighs. 
b. You will be asked to undergo a full-body DXA scan. The DXA scan will provide us 
with information about your body composition, such as how much fat, muscle, and 
bones are in your total body, arms, legs and trunk, abdomen and hip. Changes in the 
above-mentioned body composition will be documented over the course of the 
study.   
c. We will review use of the smartphone application again, and answer any questions 
you may have.   
d. This visit will mark the 2-week baseline screening period, and if still eligible you 
will be randomized to either the standard of care group or the TRE group. 
• If randomized to the Standard of Care group, you will be given guidelines 
for healthy eating habits.  
• If randomized to the TRE group, you will also be given guidelines for 
healthy eating habits, and in addition, you will be asked to restrict your 
dietary intake to 8-10 hours per day for the next 12 weeks.  
• Both groups will record all dietary intake using the smartphone application. 
e. You will meet with a dietitian at the clinic to discuss dietary expectations (standard 
of care or TRE) for the study. 
f. After this visit, the 12-week intervention period will be initiated  
g. This visit will take 1.5-2 hours. 
h. You will receive $150 for this visit. 
C. Phone Calls: During the 12-week intervention period, you will receive one phone call from 
the dietitian to check-in with you. This phone call will be 5-10 minutes.  
D. Visit 3: After 10 weeks from Visit 2, you will return to ACTRI.   
a. We will implant the continuous glucose monitor on your skin again and ask you to 
wear the wrist-worn actigraphy device (the device similar to a wristwatch) again for 
2 weeks.  
.   
b. This visit will take 30 min-1 hour.  
c. You will receive $50 for this visit. 
E. Visit 4: At the end of the 12-week intervention period, you will be asked to come to the 
ACTRI for a final visit.   
a. At this visit, you will remove the continuous glucose monitor and the wrist-worn 
actigraphy device.  
b.  We will measure your height, weight, body mass index, waist and hip 
circumference, and resting blood pressure.   
c. You will be asked to complete the same general health questionnaires from Visit 1.   
d. We will also obtain blood tests by standard vein puncture with a needle.   
e. You will be asked to undergo a muscle biopsy on one of your thighs.  
f. You will be asked to undergo a full-body DXA scan. 
g. You will meet with a study dietitian for a final check-in. 
h. This visit will take 1-2 hours.  
i. You will receive $150 for this visit. 
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
 
4 
 
As indicated above, you will receive a up to a total of $400 compensation for fully 
completing the study.  
F. Blood and muscle samples collected during the study will be stored and investigated for the 
purposes of the study. Dr. Taub will have solitary control of the stored specimens and will 
be responsible for deciding how your stored blood and muscle will be used. The specimens 
will be stored for an indefinite period of time. Additionally, they may also be used for 
future research regarding new, unforeseen research testing such as biomarkers that test for 
mitochondrial, neuroendocrine, inflammatory, and/or cardiometabolic health.   
a. These specimens and their derivatives may have significant therapeutic or 
commercial value. There are no plans to provide a compensation to you for potential 
commercial values. 
b. If you decide later that you do not want the specimens collected from you to be used 
for future research, you may tell this to Dr. Taub, who will use her best efforts to 
stop any additional studies and destroy the specimens that were collected for this 
purpose.   
c. If, as a result of participation in this study, we obtain information that could 
significantly affect your health or well-being, we will attempt to inform you of the 
existence of this information.  You may then decide if you wish to know what we 
have learned.   
d. Your samples will be stored using a de-identified code, which cannot be linked to 
you by anyone other than research personnel.  Your samples will be stored in a 
locked unit which can only be accessed by study personnel.  
e. Please note that all future research will be conducted only after the study has been 
reviewed and approved by the IRB.  
Regarding storing my blood samples indefinitely for future, unforeseen use:  
•  YES, you may store my blood samples for future research.  
•  NO, you may not store my blood samples for future research. 
 
  
Initials 
 
Regarding storing my muscle samples indefinitely for future, unforeseen use:  
•  YES, you may store my muscle samples for future research.  
•  NO, you may not store my muscle samples for future research. 
 
  
 Initials
 
 
G. (Optional) If you successfully completed the study, you may be invited to continue 
participating in optional follow-up visits (once at 6 months and once at the end of one 
year).  We may ask you to return for additional measurements, actigraphy device, CGM, 
blood work, muscle biopsy, and/or DXA scan if you choose to participate in the follow-
ups for the study.  
Regarding participating in optional follow-up visits:  
•  YES, I would like to participate.  
•  NO, I would not like to participate. / Not applicable. 
 
  
 Initials 
H. (Optional) If you have non-alcoholic fatty liver disease (NAFLD), you may be invited to 
participate in an additional screening of your liver fat through magnetic resonance 
imaging (MRI)/ magnetic resonance elastography (MRE). This will occur once at the 
beginning and once at the end of the study. 
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
5 
 
Regarding the liver MRI:  
•  YES, I would like to participate.  
•  NO, I would not like to participate. / Not applicable. 
 
  
 Initials 
 
I. We will share with you the data we collect. Your lab results will be uploaded to your 
UCSD electronic medical record as they are obtained from the lab. However, the results 
from the watch, CGM, DXA, and muscle biopsy data will not be uploaded to your UCSD 
electronic medical record; we will provide you with email attachments and/or printouts of 
these upon completion of the study (or upon withdrawal) as to avoid study bias. You will 
already have access to the app data.  
 
Study Procedure Details 
• myCircadianClock smartphone application (mCC app). 
▪ The mCC app was created by and managed by Dr. Satchidananda Panda’s lab at 
the Salk Institute for Biological Studies. It is HIPAA compliant and double-
encrypted. Consenting to use and using the mCC app is necessary and critical for 
participation in the study.  
• Activities. This study will ask you to perform tasks and respond to surveys. 
▪ The myCircadianClock app provides personalized insights into how your daily 
behaviors relate to quality of life, and to help you manage your general health 
including weight. In general, richer data entered into the app results in more 
accurate and informative insights. 
▪ To drive these insights, myCircadianClock will ask you to: Answer survey 
questions about your health behaviors, log your body weight, record what you eat 
or drink, log your exercise, and log your sleep as best as you can. 
▪ The app sends occasional reminders to complete study activities. 
▪ Educational material will be sent through the app. 
• Sensor and health data 
▪ This study can gather sensory data from your phone if you allow it to upon 
installation. 
▪ Learn More: myCircadianClock may use the built-in accelerometer in certain 
phones to passively keep track of physical activity (passive because this happens 
automatically and you do not need to enter any information). The app interprets 
accelerometer data as steps taken, or as different intensity levels of activity. The 
app can also detect when you use the phone to get an independent estimate of 
your rest or sleep period. You can also sync the app to Apple Health Kit or 
Google Fit to capture, activity, heart rate, and body temperature data. 
▪ For these activity measures to be accurate, you should carry the smartphone on 
your person as much as possible (e.g., in your pocket, or clipped to your waist). 
For instance, if the phone is left on a desk or in your car when you go for a walk, 
it will not be able to detect your walking. 
▪ The app will also use the built in GPS sensor to tag the location only when you 
log your data. This will help you to track what and where you eat, which may help 
you adjust your diet. It helps the research to account for any unusual change in 
your eating or sleeping pattern due to a change in time zone when you travel. 
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
6 
 
Change in time zones or moving to a different latitude within the same time zone 
can change the local sunrise and sunset time or local day-length, which can affect 
your circadian clock for a few days. 
▪ The use of the myCircadianClock app is not intended to evaluate your health and 
is not a diagnostic test. If you are concerned about any aspect of your health, you 
should consult with your physician.  
• Data Gathering 
▪ Our daily pattern of activity, sleep, and eating changes with season, latitude, work 
schedule, and travel. Collected data may reveal how daily behaviors affect your 
quality of life and body weight, and also advance clinical research into Circadian 
Rhythm. 
▪ Learn more: myCircadianClock helps you keep track of health behaviors such as 
diet, activity, sleep and taking your medications or supplements. 
▪ Data that you share through the app as part of the research study will create an 
unprecedented large scale database of daily behaviors and health provided by 
people just like you. 
▪ Studying this real-world data will help researchers understand how daily 
behaviors influence health in real life, with a resolution never achieved before. 
(Traditionally, these studies are done by asking people to recall answers to very 
long questionnaires on paper). 
▪ At the same time, myCircadianClock analyzes your data to provide personalized 
insights into how your daily eating, sleeping and activity patterns relate to your 
overall health, and can help you maintain a healthy lifestyle. Since the feedback is 
determined from multiple days of your routine behavior, some of these insights 
will be accessible in your phone after two weeks of data collection. 
▪ To improve data collection, the app may send you a reminder and push 
notifications. If you do not want to be bothered with these reminders, you can turn 
this option off. 
▪ By combining a personal app and a research study, myCircadianClock will 
help explore how the smartphone may be used with new kinds of clinical 
research in the future. 
•  Privacy 
▪ The following personal health information will be collected from you by the app: 
name, gender, age, email address, phone number, country, language, photos of 
food/beverages you take, activity/exercise record, timestamp of entries, and 
geographic location data from entries.  
▪ Your data will be sent to a secure database where it will be separated from your 
personal identity. 
▪ We take several steps to protect your privacy and the privacy of your app data. 
▪ To certify that you consent to participate in the study, we ask you to enter your 
name and an email address. This allows study investigators to have a record of 
who participates in the study, and to email you a copy of the signed consent 
document. 
▪ Your name and email are only used for the consent process, and are not associated 
with data collected from the app. 
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
7 
 
▪ App-generated data is associated only with a random study code, and this code is 
used in all future analyses separating it from any personally identifiable 
information. 
▪ These steps ensure that researchers analyzing the coded study data will not be 
able to connect it to any individual user. 
▪ Whenever app data is transferred to a research study computer, it will be 
encrypted so that others cannot interpret the data or associate it back to you. 
▪ Encrypted app data (stripped of personal identifiers, and associated only with a 
random code) will be sent to secure data servers used for the myCircadianClock 
research study. 
▪ Study investigators chose Amazon Web Services for this important responsibility 
because they are a world leader in the secure storage and protection of sensitive 
data. They have a proven track record of safeguarding and managing potentially 
sensitive biomedical data in accordance with regulations that govern human 
research and medical information (e.g., regulations mandated by Institutional 
Review Boards [IRB] and the Health Information Portability and Accountability 
Act [HIPAA]). 
▪ We will de-identify your data and use secure computers, but we cannot ensure 
complete privacy. 
▪ Only Dr. Satchidananda Panda, Dr. Pam Taub and their Research Teams will 
know the identities of people who participate in the study.  
▪ One potential loss of privacy would be if someone sees your data from 
myCircadianClock on your smartphone. 
▪ For security, myCircadianClock suggests that your smartphone be protected either 
by a passcode or fingerprint sensor. This ensures that only you can enter and use 
the app. 
• Utilizing Data 
▪ Your coded data will be used for research and may be shared with other 
researchers. 
▪ Study investigators will analyze coded (no personal identifiers) app data from 
everyone who agrees to participate in the myCircadianClock study, but they will 
be unable to connect it back to any individual user. 
▪ The results of this research may be published in a scientific or medical research 
journal so that others can learn from this study. Results will never be published in 
a way that would allow data to be associated with individual users. 
▪ After this study is completed, other researchers may request access to the coded 
study data (already stripped of personal identifiers), so that it can be analyzed in a 
new way to benefit medical research. Those requesting data must agree to use the 
data for research responsibly and in accordance with applicable regulations; these 
data requests will be reviewed by a group of study investigators. Amazon Web 
Services will have no oversight over future research conducted with coded study 
data. 
▪ Other researchers who are granted access to coded study data will not be able to 
connect the data back to study participants. 
▪ Study data will never be sold to any third party. 
•  Issues to Consider 
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
8 
 
▪ Your participation in this study will take 5-10 minutes per day on average. 
Entering information and responding to surveys should take on average 2-3 
minutes each day. Occasionally, tasks may take a few minutes longer (e.g., a 
longer questionnaire). 
▪ Some questions may make you uncomfortable. Any information you provide is 
completely up to you. You can decline to answer survey questions or participate 
in the app’s tasks. If a survey question makes you feel uncomfortable, you are free 
to leave questions blank. 
▪ Participation in this study does not require you to change anything related to your 
smartphone account or data plan. However, your phone must have data or wifi 
capability and must connect to internet in order to transmit data to our servers. 
The app can use either an existing mobile data plan or Wi-Fi connections: you 
may configure the app to use only Wi-Fi connections if you wish to limit impact 
on your data usage. 
• Safety and Legality 
▪ As with any smartphone app, follow prevailing laws about when and where you 
use your smartphone. Similarly, follow local and federal regulations about the 
usage of a smartphone in specific areas.  
▪ Additionally, the app should not be used in any capacity to perform or document 
illegal activity. The Salk Institute for Biological Studies, Dr. Satchidananda Panda 
and all members of his research team, including collaborators, are not liable for 
any illegal activity that is performed, captured, or stored by the myCircadianClock 
app. 
• Re-contacting: You may be randomly selected for contact by the authorized 
researcher via email or phone to verify your identity or clarify some of your 
answers to surveys.  
• Study Survey 
▪ Some of the tasks in this study will require you to answer survey questions about 
various health and lifestyle factors. 
▪ myCircadianClock will collect some of its data on your health behaviors 
through short survey questions, such as: Did you forget to eat breakfast today? 
When did you wake up this morning? Do you feel sleepy during the day? 
▪ Occasionally, there will also be longer surveys that evaluate aspects such as 
your work habits, quality of life, and sleeping pattern. 
▪ For dietary information, myCircadianClock will prompt you to take pictures of 
every food, beverage, water, medication, and supplement(s) you take. 
▪ When picture taking is difficult or socially awkward as in a meeting, if you forgot 
to take picture or you are repeatedly eating the same item, you can also enter the 
information textually from a different screen. 
▪ In general, more data entered into the app results in more accurate and informative 
personalized insights. 
• Study Tasks 
▪ Some other interactions with the app are designed to maximize both data gathering 
and the feedback you receive. 
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
9 
 
▪ To gather additional information, including but not limited to activity (step 
counts/distance), heart rate, height and weight, you can sync other smartphone 
apps and sensory devices (such as Apple Health Kit and Google Fit) with 
myCircadianClock. You also have the choice to allow the myCircadianClock app 
to access your location in order to determine the local time. You can allow or deny 
these features when you first install the myCircadianClock app, and are able to 
change these settings at any time.  
▪ myCircadianClock will also ask about some information that requires a brief task 
away from the smartphone, such as: your weight, your height, your waist 
circumference (occasionally), and your blood pressure. The app also has optional 
fields to enter relevant results from blood tests and urine samples including: blood 
glucose, lipid panels (total cholesterol, LDL, HDL, triglycerides), Hemoglobin 
A1c, Fibrinogen, C-Reactive Protein, Homocysteine, and ketone bodies if you 
wish to monitor these parameters.  
▪ All data entered is used solely for tracking purposes, not diagnosis. The Salk 
Institute for Biological Studies, Dr. Satchidananda Panda and his lab are not 
responsible for providing medical advice and are not liable for the medical care of 
participants. Participants should contact a medical professional for medical advice.  
▪ The myCircadianClock app provides personalized feedback in the form of graphs 
and text to display your progress, and provide insights into your health behaviors. 
▪ The app summarizes data about how food, sleep or activity patterns in specific 
time of the day are associated with your health and wellbeing. These insights may 
help you understand your health behaviors better, and help you manage your 
health. Viewing the graphs and text is optional but may be useful or interesting to 
you. 
▪ For the passive sensing of your physical activity in some phone models to be 
accurate, it is important to carry your smartphone on your person (e.g., in your 
pocket, or clipped to your waist). Carrying your phone will also help you log food, 
beverage, water and activity data as soon as these events occur. 
▪ In your Profile within myCircadianClock, you can set reminders for yourself to 
complete app activities. In general, more data entered in the app results in more 
accurate and informative insights. 
• Meals, activity, and sleep: The smartphone application myCircadianClock (mCC app) 
will serve as an electronic food, activity, and sleep diary.  
o On the server side, a sub-study dashboard will be created for this specific project. 
Clinical coordinators from Dr. Taub’s research team will have password-protected 
access to the study data. In the study summary dashboard, the participant’s study 
code and the date of activation of the app will be shown along with their daily log. 
If a participant fails to log any food data for more than 1 day, the dashboard flags 
the participant and sends an alert to the coordinator. The coordinators will login to 
the dashboard at least twice weekly to monitor food intake data, and follow up 
with flagged participants as necessary.  
o You will self-select an interval of 10 hours per day within which to consume your 
food. You can easily track your progress of the daily eating pattern with the time-
stamping feature of the app that offers a visual summary.  
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
10 
 
o If you have any difficulty logging data, or have questions about any of the 
features of the app, you will be able to contact the study coordinator through the 
feedback feature of the app. The questions will be delivered to a HIPAA 
compliant email server specifically set up for this study.  
• Questionnaires 
o Pittsburgh Sleep Quality Index (PSQI)  
o Munich Chronotype Questionnaire (MCTQ)  
o Beck depression inventory (BDI) 
o Epworth Sleepiness Scale (ESS) 
o Short Form-36 Quality of Life (SF-36) 
o mCC app-related surveys 
• Fasting: We will ask you to fast for the blood draw and muscle biopsy, which means you 
will be asked to not consume any food or beverages (except for water) 12 hours prior to 
your visit 
• Blood draw: A total of approximately 1 cup (200ml or 16 tablespoons) will be collected 
from you for the entire study, which is less than what is collected at blood donations. 
There is the possibility of a blood test being repeated, which would mean the total 
amount of blood drawn will be more than 1 cup (or 16 tablespoons).  
o A needle or intravenous catheter will be used to draw blood from a vein in your 
arm at the study visits. An intravenous catheter is a thin, flexible tube that is 
attached to the needle, which gets inserted into a vein and is held in place with 
tape. This allows the needle to be inserted only once with the case of multiple 
blood samplings.  
o We will test for the following with the blood draw: 
▪ CMP = comprehensive metabolic panel (kidney function, electrolytes, 
glucose, and liver function)  
▪ CBC = complete blood count (white and red blood cells 
(hemoglobin/hematocrit), and platelets (“clotting cells”)  
▪ TSH = thyroid-stimulating hormone (thyroid gland function)  
▪ HbAa1c= glycosylated hemoglobin (a measure of “average” blood sugar) 
▪ Insulin= body’s response to blood sugar  
▪ hs-CRP= high sensitivity C-Reactive Protein (a measure of inflammation) 
▪ Lipoprofile by nuclear magnetic resonance (NMR) = detailed assessment 
of cholesterol profile with lipid panel 
▪ Apo B/A = apolipoprotein B/A (a component related to cholesterol and 
cardiovascular disease development) 
o Blood draws will occur during baseline and at the end of the study. 
• Urine pregnancy test: Will be performed in women of child-bearing potential (who are 
still menstruating) at Visit 1 and if positive, will result in exclusion from study 
participation. 
• Randomization: Given that you will be randomized to one of two groups, if you are in 
the standard of care group only, it is unlikely that you will experience the potential 
benefits of the intervention group (TRE).  
• Continuous glucose monitoring (CGM): All participants will be implanted with a 
CGM, and be instructed on its use. 
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
11 
 
o You will wear the CGM for one week prior to the start of the 12-week 
intervention period and for one week before the intervention period ends. 
o The CGM is composed of a quarter-sized sensor that lies on top of the skin and a 
thin filament that is inserted under your skin. 
o CGM measures the glucose (sugar) in your body by using a sensor that will be 
placed under your skin. CGMs estimate blood glucose levels with high accuracy 
that correlates with those obtained from either venous or capillary blood draws.  
o The CGM will be implanted in the following steps: 
▪ The upper arm area of your choosing will be cleaned with alcohol swabs. 
The area will be allowed to dry (10-20 seconds).  
▪ Then, an adhesive (such as SkinTac) will be applied to that clean area. 
This area will become sticky and tacky (30 seconds-1 minute).  
▪ The CGM will then be implanted onto the skin through a device applicator 
that has a needle. The device applicator will be placed on top of the 
chosen arm area and will be pressed against the skin. This will bring the 
CGM sensor in contact with the skin and will trigger a needle within the 
device applicator to release. This needle inserts the thin filament in the 
superficial layer under the skin. The needle automatically retracts so it will 
not stay in you. The filament will remain under your skin until the whole 
CGM is removed. Implanting the CGM takes about 10 seconds.  
▪ Then, another adhesive tape (such as Rockadex- which is similar to 
kinesiology tape) will be placed around the CGM on the skin to secure the 
area.  
▪ The CGM will then be activated and registered with its reader system.  
▪ You can go about your normal daily activities (shower, work-out, etc) as it 
will not interfere with your daily routine.  
• Wrist-worn actigraphy: This is similar to a wrist watch and it measures activity. It also 
functions as a wrist watch and will display the time. 
o To measure habitual physical activity and sleep, participants will wear an 
accelerometer for one week prior to the start of the 12-week intervention period 
and for one week before the intervention period ends  
o You will be asked to wear this actigraphy watch 24/7 (especially during sleep). As 
it is water-resistant (not water-proof), you will be asked to take it off when you’re 
submerged in water (showering, swimming, surfing, etc) and to put it back on 
when you’ve finished those tasks. You may also remove it if you find that it is 
causing skin irritations.  
o The actigraphy data will also be used to measure sleep onset, sleep duration and 
associated parameters (sleep efficiency and sleep fragmentation).  
o You will also complete a short sleep log every morning on the mCC app to record 
self-reported quality of sleep. 
• Muscle Biopsy: A biopsy of your leg muscle will be obtained using a special needle. 
o To do a muscle biopsy, an area of skin and the deeper tissues on the outer front 
portion of either of your thighs will be numbed using anesthetic (xylocaine) and a 
small (1/4 inch) incision made with a scalpel. There is a chance that a small scar 
will form. There is also a very small chance that the scars from the biopsy sites 
may become thick (hypertrophy). 
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
12 
 
o The numbing medication, (xylocaine) will be given under the skin to minimize 
the pain. You may feel some discomfort like a burning or stinging sensation while 
the anesthetic is being injected  under the skin. The risks of using local anesthesia 
may include temporary numbness, tingling sensations, and potential allergic 
reaction A very small amount of numbing medication is used so it is very unlikely 
that you will have any side effects from this medication.  
o The special biopsy needle will be inserted through the incision and into your thigh 
muscle several times and a small amount of tissue will be removed (about the size 
of a small pea).  
o After the biopsy is completed, deep pressure will be applied to the site for 
approximately 20 minutes to reduce the risk of bleeding and then a steri-strip tape 
will be used to close the incision.  
• Dual Energy X-ray absorptiometry (DXA) scan: DXA scan will be done using a 
Hologic discover W densitometer. 
o You will be asked to change into a gown that we will provide. Then, you will be 
asked to lie supine (lie on your back) on the DXA scan table for 10-15 minutes 
until the whole-body scan is complete. Then, you will be asked to change into 
your clothes.   
o As with any form of radiation, there is a carcinogenic or genetic risk. However, 
the risks are assumed to be minimal as this is a low-energy X-ray modality that 
uses a low dose to image the body. The total exposure resulting from these 
imaging studies is calculated to be approximately 0.09000mSv. This amount is 
less than you would receive from one year of natural exposure in the San Diego 
area, which is approximately 1.6 mSv. See the section regarding risks below for 
more details.  
• Magnetic resonance imaging (MRI)/Magentic resonance elastography (MRE): As an 
optional part of the study, we will perform an MRI scan (without intravenous contrast) of 
your liver.  
o You will be asked to change into a gown that we will provide. Then, you will be 
asked to lie on the MRI scan table for 60 minutes until the scan is complete.  
o A vibrating paddle will be placed over your abdomen 
o We will measure the amount of fat in your liver using these MRI images.   
 
How much time will each study procedure take, what is your total time commitment, and how 
long will the study last? 
Your total time commitment in the study will be about 3.5 months (2 weeks of baseline with 12 
weeks of intervention (standard of care or TRE) for a total of 14 weeks). Your total time 
commitment for each visit will be about 1-2 hours per visit (7-14 hours for all visits).  
 
What risks are associated with this study? 
Participation in this study may involve some added risks or discomforts. The risks of this study 
include:  
a) Surveys/Questionnaire: Some questions may make you uncomfortable. Any 
information you provide is completely up to you. You can decline to answer survey 
questions or participate in the app’s tasks. If a survey question makes you feel 
uncomfortable, you are free to leave questions blank. Depending on the scores on one 
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
13 
 
of the questionnaires regarding your mood, you might be asked to complete an 
interview with a psychiatrist or clinical psychologist to determine to level of your 
depression. This will also occur if study-staff become concerned that you are at high-
risk for suicide based on their conversations with you. If you are found to have 
significant clinical depression or thoughts of suicide, your referring internist or 
cardiologist will be notified and you will be referred to appropriate professional 
treatment for your depression. 
b) Smartphone use: As with any smartphone app, use your common sense and follow 
prevailing laws about when and where you use your smartphone. Just as you would not 
text while driving, do not interact with the app while driving or doing any other 
activities which could result in injury. You can always wait until you are in a safe place 
to perform any app-related tasks.  
c) Randomization: Given that you will be randomized to one of two groups, if you are 
randomized into the standard of care group, you may not experience the potential benefits 
of the intervention group (TRE).  
d) Blood draw 
a. Bruising 
b. Arterial puncture 
c. Pain 
d. Nerve damage 
e. Re-bleeding 
f. Allergy 
g. Blood vessel inflammation, infection, and/or pain 
h. Fainting  
i. Anxiety/fear 
e) Wrist-worn actigraphy device: You will be asked to wear a wrist-worn actigraphy 
device. Despite all the measures taken in material selection, design and manufacturing 
to ensure biocompatibility, some people may not tolerate wearing the device and can 
develop skin irritation. If this happens to you, please notify the study personnel 
immediately. The instructions for use of the watch advise on the measures you can take 
to limit the chance of experiencing any problems (such as tightness of wearing and 
regular cleaning). 
f) Use of continuous glucose monitor 
a. Redness at the sensor insertion site 
b. Skin irritation (redness, swelling) 
c. Local infection, inflammation, pain or discomfort 
d. Bleeding at the glucose sensor insertion site 
e. Bruising, itching, scarring or skin discoloration, blood clot under the skin, tape 
irritation, and sensor or needle fracture during insertion, wear or removal. 
g) Muscle biopsy 
a. You may also feel some pain in your muscle when the tissue is removed. After the 
anesthetic wears off, the biopsy site may be mildly tender for 1-3 days. It is likely 
that a scar may form at the incision site. The scar from the muscle biopsy will be 
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
14 
 
about 1/4 inch long. There is a very small chance that the scars from the biopsy 
sites may become thick (hypertrophy). 
b. The risks of using local anesthesia may include temporary numbness, tingling 
sensations, and potential allergic reaction. 
c. There is also a small chance of bleeding or infection at the biopsy site. 
d. There is a chance fainting could occur during the muscle biopsy.  
e. Your muscle will be studied in the laboratory. Some of your muscle may be 
stored indefinitely and saved for future analysis. A total of two biopsies will be 
performed, one at the beginning of the study and one at the end of the study.  Dr. 
Taub and her team have performed over 200 muscle biopsies with no 
complications. 
h) Dual energy x-ray absorptiometry (DXA) scan: During your participation in this research 
study, you will be exposed to radiation from scheduled DXA scans. The total exposure 
resulting from these imaging studies is calculated to be approximately 0.09000mSv. As 
with any form of radiation, there is a carcinogenic or genetic risk. However, the risks are 
assumed to be minimal as this is a low-energy X-ray modality that uses a low dose to 
image the body. This amount is less than you would receive from one year of natural 
exposure in the San Diego area, which is approximately 1.6 mSv. Cumulative exposure 
from radiation may increase your risk of developing certain types of cancer in the future. 
The principal investigator for this research study has determined and verified that some 
of the x-rays and/or imaging scans prescribed for this study would typically be performed 
as part of the standard medical care required to adequately monitor your current illness. If 
you are especially concerned with radiation exposure, or you have had a lot of x-rays or 
imaging scans already, you should discuss this with the principal investigator for this 
study, Dr. Pam Taub , or your regular doctor. 
i) Reduced daily feeding period (from ≥ 12 hours per day to 8-10 hours per day) 
a. Hunger 
b. Fatigue 
c. Low blood sugar 
j) Inability to start cholesterol-lowering, blood pressure lowering, and blood sugar lowering 
medications or undergo dose adjustments of these medications during the study period 
a. This could lead to incompletely controlled cholesterol, blood pressure, and/or 
blood sugar values during the study period which could have either early (e.g. 
symptoms related to high or low blood pressure, and/or high or low blood sugars) 
and/or long-term risks (e.g. potentially increasing overall long-term risk of 
cardiovascular disease/events).   
b. It is advised that you take necessary action in interest of your health; for example- 
discussing with your primary care provider or postponing the start of the study 
until you are on stable doses. You may also be withdrawn from the study if 
medications change and impact study results.  
k)  Magnetic resonance imaging of liver 
a. Injury/complications associated with the presence of implanted devices or 
metallic objects which are not compatible with MRI imaging. We will review a 
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
15 
 
list of MRI Unsafe devices and objects with you prior to your enrollment in the 
study. You will be excluded from the study if any of these devices or objects are 
present. Presence of MR Safe devices will be allowed, and MR Conditional 
devices will be reviewed on an individual patient basis by the principal 
investigator. Examples of injuries/complications related to the presence certain 
devices and objects include: device movement, burns, and device malfunction. 
b. Anxiety 
c. Claustrophobia 
d. Discomfort due to loud noise 
e. Discomfort due to vibrations of paddle for MRE 
l) Unscheduled visits: There may be the possibility of having subjects return for 
unscheduled visits in between the scheduled visits. This would be for the following 
reasons: PI discretion, if the bloodwork needs to be redrawn due to lab or processing 
errors, and/or reapplication of the continuous glucose monitor if it fell off or did not 
record data. 
m) A potential loss of confidentiality. The UCSD Institutional Review Board (IRB), the 
FDA, and other government agencies may inspect the study records.  To minimize the 
risk of a potential loss of confidentiality, subjects will be assigned a unique subject code 
and their blood samples will be assigned a different unique specimen code.  A separate 
paper document will link patient identifiers with subject codes and specimen codes.  This 
document will be kept in a secure location in a locked cabinet.  Only the PI and study 
coordinator will have the key to the cabinet.  No research documents will have any 
patient identifiers and will only be labeled with the unique assigned subject codes. 
Because this is a research study, there may be some unknown risks that are currently 
unforeseeable. You will be informed of any significant new findings. You will be told if any 
important new information is found during the course of this study that may affect your desire to 
continue. 
 
What are the alternatives to participating in this study? 
This study is optional. You may choose not to participate in this study at any time.  
 
What benefits can be reasonably expected? 
There may or may not be a direct benefit to you from this study.   
For those randomized into the TRE group, the potential benefit is that by engaging in TRE, you 
may see overall improvement in cardiometabolic risk factors and decreases and biomarkers, 
which may improve your overall health and reduce your risk for cardiovascular disease. There 
may also be improvements in sleep quality and mood.  
For those randomized into the standard of care group, you may not experience any benefits.  
The potential benefits to society in general include improved understanding of the effects of 
time-restricted eating on the health of individuals with metabolic syndrome. 
 
Can you choose to not participate or withdraw from the study without penalty or loss of 
benefits? 
Participation in research is entirely voluntary. You may refuse to participate or withdraw at any 
time without penalty or loss of benefits to which you are entitled. If you decide that you no 
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
16 
 
longer wish to continue in this study, you will be requested to contact the study coordinator and 
inform the research team of your desire to withdraw from the study. At time of withdrawal, you 
will be asked to return for final visit(s) involving a wearing actigraphy device, wearing CGM, 
blood draw, muscle biopsy, and/or DXA scan. You may also be withdrawn from the study if you 
do not follow the instructions given you by the study personnel. You may be withdrawn from the 
study if Dr. Taub believes that it is in your best medical interest.  You will be told if any 
important new information is found during this study that may affect your wanting to continue. 
 
Will you be compensated for participating in this study? 
In compensation for your time and travel, you will receive up to $400 for fully participating in 
the study.  
Visit 1 - $50 
Visit 2 - $150 
Visit 3 - $50 
Visit 4 - $150 
 
Are there any costs associated with participating in this study? 
There will be no cost to you for participating in this study. We will provide free parking for the 
study visits. We do not provide compensation for cell phones, cell phone data, or Wi-Fi used for 
the app. 
 
What if you are injured as a direct result of being in this study? 
If you are injured as a direct result of participation in this research, the University of California 
will provide any medical care you need to treat those injuries. The University will not provide 
any other form of compensation to you if you are injured. You may call the Human Research 
Protections Program Office at 858-246-4777 for more information about this and to inquire 
about your rights as a research subject or to report research-related problems. 
 
What about your confidentiality? 
Research records will be kept confidential to the extent allowed by law. Your research records 
will be labeled with a code number. The list that matches your name with the code number will 
be kept in a locked file in the research team’s office. Any research records that identify you will 
be kept only as paper records in a secure ACTRI location, or as files behind the secure UCSD 
computer firewall. Any presentations or publications from this information will not identify you. 
We will collect the following personal health information: name, age, gender, date of birth, 
medical record number, current and past medical history, list of current medications, and location 
data from the mCC app.  Research records may be reviewed by the UCSD Institutional Review 
Board, the NIH, the FDA, and the Federal Office of Human Research Protections. 
 
Who can you call if you have questions? 
Dr. Pam Taub and/or her research team designee has explained this study to you and answered 
your questions.  If you have other questions or research-related problems, you may reach Dr. 
Pam Taub at 858-246-2497 during the day, or call 619-290-1252 (pager) after 5:00 PM. 
 
Principal Investigator (UCSD) 
Pam Taub, MD 
858-246-2497 
Co- Investigator (Salk) 
Satchidananda (Satchin) 
858-453-4100 ext 1949 
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023

IRB 181088 
17 
 
Panda, PhD 
Research Associate (Salk) 
Emily Manoogian, PhD 
858-453-4100 ext 1077 
Study Coordinators(UCSD) 
David Van, BS 
858-246-2342 
 
A member of our research team is available to answer any questions you may have concerning 
the application. You can contact them directly through the app or at the following email address: 
circadian@mycircadianclock.org.  
 
This study is fully funded by grants from the National Institutes of Health (NIH).  The 
investigators have no financial conflicts of interest to disclose.  For questions, please contact the 
research coordinator at 858-246-2510 and she will connect you the appropriate staff at the 
Conflict of Interest Committee. 
 
Re-contacting. You may also be contacted in the future for study-related follow-up questions 
and/or to inform you of other research studies you may be eligible for. Please check the boxes 
below as appropriate. 
 
• YES, you may contact me 
in the future for study-
related follow-up 
• YES, you may contact me 
about other research studies 
I may be eligible for 
• NO, do not contact 
me about these things 
after the study ends 
 
Your Signature and Consent 
You have received a copy of this consent document and a copy of the “Experimental Subject's 
Bill of Rights” to keep. 
 
By signing below, you agree to participate in this study. 
 
________________________________________________ 
Subject's name (Print)  
 
 
 
 
 
 
________________________________________________ 
_______________ 
Subject’s Signature 
 
 
 
 
 
                        Date  
 
 
 
 
________________________________________________ 
 
Researcher obtaining consent (Print)  
 
 
 
_________________________________________________ 
_______________ 
Signature of Researcher obtaining consent 
 
 
 
 
Date 
 
Protocol #181088 | v18 | Approved: Dec 02, 2021 12:00 AM MST | Expires: Oct 08, 2023