Time to Eat Study - Pilot
Phase: NA
Conditions: Overweight
Sponsor: University of Florida

 
 
Version 7_Dated 2018-07-06 
 
Title:  Time to Eat Study – Pilot  
 
 
Investigators:  
Stephen Anton, PhD  
 
 
 
Marco Pahor, MD 
 
 
 
Todd Manini, PhD 
 
 
 
Christiaan Leeuwenburgh, PhD  
 
 
 
Troy Donahoo, MD (Study Physician) 
 
 
1. 
Abstract: 
 
Growing evidence shows that low-grade chronic inflammation, characterized by 
elevations in plasma C-reactive protein and particularly Interleukin-6 (IL-6), is an 
independent risk factor of disability, impaired mobility, and lower walking speed. Low-
grade chronic inflammation is a modifiable risk factor. However, it is unknown whether 
interventions that reduce the levels of inflammatory markers per se improve mobility, or 
avert decline in mobility in older persons. 
There also remains an important need for interventions that can improve 
unhealthy changes in body composition that occur during aging. Given the known loss 
of lean mass that occurs during both aging and continuous calorie restriction, alternative 
approaches are needed to help older adults lose unhealthy weight while retaining larger 
amounts of lean mass.  Our recent review suggests that a specific form of intermittent 
fasting, time restricted feeding, results in weight and fat loss (even when caloric intake 
is not limited), without significant loss of lean mass. This would be an optimal outcome 
for overweight, older adults and should also result in a reduction in inflammation and 
improvement in mobility.  
To date, no study has examined the effects of time restricted feeding in older 
adults. Preliminary data regarding feasibility need to be gathered before a full scale trial 
can be effectively designed and implemented. Thus, the primary aims of this pilot study 
are to evaluate the safety and feasibility of time restricted feeding in an older adult 
population. The Time to Eat Pilot Study will also assess the variance of inflammatory 
markers, walking speed, physical and cognitive function, grip strength, body 
measurements, perceived fatigability, and activity level. This allows the refinement of 
the design, recruitment yields, target population, adherence, retention, and tolerability of 
a larger scale study. 
For this 4-week pilot study, we will recruit 10 overweight, older adults who are at 
risk for, or with, mobility impairment, as measured by slow gait speed and self-reported 
mobility difficulty and self-reported sedentary lifestyle to complete.  All participants will 
receive the time restricted feeding intervention, which will consist of fasting for 
approximately 16 hours per day. 
 
    

 
 
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2. 
Specific Aims: 
 
Growing evidence from our group and others shows that low-grade chronic 
inflammation, characterized by elevations in plasma C-reactive protein (CRP) and 
particularly interleukin-6 (IL-6) [1-7] is an independent risk factor for disability, impaired 
mobility, and slow walking speed [1, 6-11]. Low-grade chronic inflammation is a 
modifiable risk factor. However, it is unknown whether interventions that reduce the 
levels of inflammatory markers per se improve mobility, or avert decline in mobility in 
overweight, older persons 
 
Conduct a pilot study of 10 overweight, older sedentary persons at risk for mobility 
decline to assess:  
(i) 
Feasibility of the study intervention in the study population 
a. adherence and retention 
b. tolerability 
c. recruitment yields  
(ii) 
Variance in the following: 
a. inflammation (IL-6 and CRP) level 
b. walking speed 
c. body mass index 
d. waist circumference 
e. grip strength 
f. fatigability level 
g. activity level 
h. cognitive functioning as measured by the MoCA 
i. perceived exertion during the 6 min walk 
j. health-related quality of life.  
 
 
3. Background: 
 
Aging is associated with a host of biological changes that contribute to a 
progressive decline in cognitive and physical function, ultimately leading to a loss of 
independence, and increased risk of mortality.  To date, caloric restriction (i.e., a 
reduction in caloric intake without malnutrition) is the only non-genetic intervention that 
has consistently been found to extend both mean and maximal life span across a 
variety of species [12].  Although attenuated, these effects remain present even when 
moderate caloric restriction (20-40%) is implemented in middle-age mice [13].   
Importantly, prolonged caloric restriction has also been found to delay the onset of age-
associated disease conditions such as cancer and diabetes in rodents [14] and in 
nonhuman primates [15].  Thus, findings from animal studies, including recent primate 
studies, suggest prolonged caloric restriction has the potential to extend health-span 
and thereby increase quality of life.   
 
In recent studies conducted in overweight humans, caloric restriction has been 
shown to improve a number of health outcomes including reducing several cardiac risk 

 
 
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factors [16-18], improving insulin-sensitivity [19], and enhancing mitochondrial function 
[20]. Additionally, prolonged caloric restriction has also been found to reduce oxidative 
damage to both DNA [21-23] and RNA, as assessed through white blood cells [23]. 
Thus, findings of initial human clinical trials appear to support the promise of caloric 
restriction demonstrated in animal studies, at least in overweight adults.   
 
Despite these health promoting biological changes, most individuals have 
difficulty engaging in caloric restriction over the long-term [24].  Findings from weight 
loss interventions conducted over the past few decades indicate that the vast majority of 
individuals who lose weight regain this lost weight over the course of one to five years. 
An additional concern about implementing calorie restriction in older adults is that the 
weight loss is comprised of both fat and lean tissue; however, the weight that is 
frequently regained is primarily comprised of fat. This can lead to a situation where the 
individuals body composition is worse than when they initiated a weight loss program.  
 
Due to poor long-term compliance and loss of lean tissue that occurs with calorie 
restriction, there is a need to explore the potential of alternative approaches for reducing 
body weight, specifically body fat, in overweight older adults. One alternative dietary 
approach that may produce similar biological changes as caloric restriction that has 
received increasing interest from the scientific community is Intermittent Fasting. In 
contrast to traditional caloric restriction paradigms, food is not consumed during 
designated fasting time periods but is typically not restricted during designated feeding 
time periods. The length of the fasting time period can also vary but is frequently 12 or 
more continuous hours.   
 
Evidence that this approach may have beneficial effects on longevity first 
appeared several decade ago [25].  Since this time, a growing body of literature 
suggests that fasting periods and intermittent fasting regimens can trigger similar 
biological pathways as caloric restriction (i.e., increased autophagy and mitochondrial 
respiratory efficiency), which can result in host of beneficial biological effects including 
increased circulation and cardiovascular disease protection, modulation of reactive 
oxygen species and inflammatory cytokines, as well as antimutagenic, antibacterial, and 
anticarcinogenic effects [26]. 
 
We recently completed a review of the literature on the effects of intermittent 
fasting on changes in body composition in overweight individuals [27]. For the time 
restricted feeding approach, we identified four clinical trials that measured changes in 
participant’s body composition before and after they received this intervention. An 
important finding of our review was that participants who engaged in time restricted 
feeding lost a significant amount of body fat without loss of lean tissue in three of the 
four clinical trials included in our review. These findings suggest that time restricted 
feeding results in weight and fat loss (even when caloric intake is not limited) without 
significant loss of lean mass. 
 
Despite these promising findings, no study to date has examined the effects of 
time restricted feeding in overweight, older adults. Thus, there is a need to understand 

 
 
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whether a time restricted eating pattern could produce similar beneficial changes on the 
body composition of older adults, as well as reduce inflammation and improve mobility. 
Given the known loss of lean mass that occurs during both aging and continuous calorie 
restriction, time restricted feeding regimens may be an effective approach to help 
overweight, older adults lose unhealthy weight while retaining larger amounts of lean 
mass.   
 
To date, no study has examined the effects of time restricted feeding in older 
adults. Preliminary data regarding feasibility need to be gathered before a full scale trial 
can be effectively designed and implemented. Thus, the primary aims of this pilot study 
are to evaluate the safety and feasibility of time restricted feeding in an overweight, 
older adult population. The Time to Eat Pilot Study will also assess the variance of 
inflammatory markers, walking speed, physical and cognitive function, grip strength, 
body measurements, perceived fatigability, and activity level. This allows the refinement 
of the design, recruitment yields, target population, adherence, retention, and tolerability 
of a larger scale study. 
 
 
4. 
Research Plan: 
 
4.1 Design 
 
This is a pilot study of 10 overweight, older sedentary persons at risk for mobility decline 
to assess feasibility of an intermittent fasting intervention program within this study 
population and evaluate changes in inflammatory level, walk speed, physical and 
cognitive function, grip strength, body measurements, perceived fatigability, and activity 
levels.  
 
 
4.2 Eligibility Criteria 
Inclusion criteria 
• Consent to participate in the study 
• Men and women ≥ 65 years old 
• Self-reported difficulty walking ¼ mile or climbing a flight of stairs 
• Self-reported sedentariness (<30 minutes structured exercise per week) 
• Walking speed <1 m/sec on the 4 m walk test 
• Able to walk unassisted (cane allowed) 
• Have a body mass index between 25 – 40 kg/m2 (inclusive) 
 
Exclusion criteria 
• Current dietary habits 
o Fasting >12 hours per day 
o Actively trying to lose weight by participating in formal weight loss program 
or significantly restricting calorie intake  
o Weight loss > 5 lbs in the past month 
• Medical history or conditions 

 
 
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o Resting heart rate of >120 beats per minute, systolic blood pressure > 180 
mmHg or diastolic blood pressure of > 100 mmHg 
o Unstable angina, heart attack or stroke in the past 3 months 
o Continuous use of supplemental oxygen to manage a chronic pulmonary 
condition or heart failure 
o Rheumatoid arthritis, Parkinson’s disease or currently on dialysis 
o Active treatment for cancer in the past year 
o Insulin dependent diabetes mellitus 
• Taking medications that preclude fasting for 16 hours (e.g. must be taken with 
food at least 12 hours apart) 
• Any condition that in the opinion of the investigator would impair ability to 
participate in the trial 
 
4.3 Screening, assessments, and follow-up  
Table 1. Schedule of Assessments 
 
Phone 
screen 
(phone) 
Screen/ 
Baseline 
(clinic) 
Week 1 
(phone) 
Week 2 
(phone) 
Week 3 
(phone) 
Week 4 
(clinic) 
Verbal consent & phone 
screening 
X 
 
 
 
 
 
Consent 
 
X 
 
 
 
 
Review of medical 
history* 
 
X 
 
 
 
 
4 m walk* 
 
X 
 
 
 
 
Height*, weight*, waist 
circumference 
 
X 
 
 
 
X 
Blood pressure*, 
pulse*, temperature 
 
X 
 
 
 
X 
6 minute walk 
 
X 
 
 
 
X 
Grip strength 
 
X 
 
 
 
X 
Fasting blood collection  
 
X 
 
 
 
X 
Montreal Cognitive 
Assessment (MoCA) 
 
X 
 
 
 
X 
Fatigability 
Questionnaire 
 
X 
 
 
 
X 
SF-12 
 
X 
 
 
 
X 
Distribute / collect 
accelerometer 
 
X 
 
 
 
X 
Distribute food intake 
time and sleep diaries 
 
X 
 
 
 
 
Review food intake time 
diary 
 
 
X 
X 
X 
X 
AE review 
 
 
X 
X 
X 
X 
Satisfaction survey & 
exit interview 
 
 
 
 
 
X 

 
 
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* Must be completed to confirm eligibility prior to completing other baseline 
measurements.  
 
Recruitment and Telephone Screening 
Potential participants will be recruited from the general population in the North/Central 
Florida area through general mailings and advertisements and targeted outreach to 
those who have consented to participate in the Claude D. Pepper Recruitment Registry 
(IRB#417-2007).  
 
Potential participants who verbally consent to complete the telephone screening are 
assessed of the main eligibility criteria, including: 
• Age 
• Self-reported sedentariness 
• Self-reported mobility difficulty 
• Self-reported height and weight 
• Medical history 
• Current dietary pattern 
 
Screening/Baseline Clinic Visit 
Those who qualify based on the telephone screening are invited to take part in the in 
person clinic visit.  During this visit, informed consent is obtained and the following 
assessments are completed: 
• Measurement of height and weight to determine body mass index  
• 4 m walk test  
 
If the participant is eligible to participate based on these assessments, he/she will then 
continue with the remainder of the baseline assessments, including: 
• Measurement of waist circumference 
• 6 minute walk test 
• Grip strength test 
• Collection of blood sample for the measurement of inflammation 
biomarkers (IL-6 and CRP) 
• Montreal Cognitive Assessment 
• Fatigability Questionnaire 
• SF-12 
• Distribute food intake and sleep time record diaries 
• Distribute activity monitor 
 
Weekly Phone Contacts 
Participants will be contacted by phone at the end of weeks 1, 2, and 3. The following 
will be reviewed: 
• Time of first and last food or drink consumption over the past week 
• Changes in health (adverse events) 

 
 
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Study staff will provide participants counseling if he/she is experiencing difficulty in 
adhering to the study intervention.  
 
Additional phone calls may be made as needed, if the participant requires additional 
support or guidance in adhering to the study intervention.   
 
Week 4 Follow-up Clinic Visit 
Following 4 weeks of the study intervention, participants will complete a follow-up clinic 
visit.  At this visit, baseline assessments are repeated and participants will be asked to 
report any changes in health since initiating the study. Additionally, participants will be 
asked to complete a satisfaction questionnaire and an exit interview about their 
experience during the study.   
 
4.4 Intervention 
Intermittent Fasting 
Study participants will be asked to fast for a target of 16 hours per day for a period of 4 
weeks.  The first week will involve of a ramp up to a full 16-hour fasting period (Days 1-3 
fast for 12-14 hours per day, Days 4-6 fast for 14-16 hours per day, Days 7-28 fast for 
16 hours per day).  Participants will be allowed to consume calorie-free beverages, tea, 
black coffee, sugar-free gum, and they will be encouraged to drink plenty of water 
throughout the entire intervention period.  Participants will be asked to record the time of 
first and final food/drink consumption each day.   
 
4.5 Outcomes 
Adherence and Retention 
Adherence to the study intervention is measured using food intake time diary.  
Participants are considered compliant to the study intervention if he/she fasts between 
14 – 18 hours per day during weeks 2 - 4. Retention is measured by drop-out rate.   
 
Tolerability 
At each follow-up contact (either by phone or in person), participants are asked about 
any changes to their health or physical function since the previous contact. The 
changes are documented on the adverse event log.  Participants are also asked about 
problems or challenges in following the study intervention. Any reported difficulties will 
be recorded on a progress note.  
 
6 Minute Walk Test 
The 6 Minute Walk test measures the amount of distance the participant can complete 
on a standard walking course in six minutes without running or overexerting themselves. 
Contraindications for test administration and stopping rules based on American 
Thoracic Society will be followed [28]. The walk test is completed at baseline and Week 
4.  
 
 

 
 
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Grip Strength 
Isometric hand grip strength is a commonly used measure of upper body skeletal 
muscle function and has been widely used as a general indicator of functional status 
[29, 30] and is completed at baseline and Week 4.  
 
Montreal Cognitive Assessment (MoCA) 
The Montreal Cognitive Assessment is a 30-point assessment of mild cognitive 
impairment, which assesses the domains of attention and concentration, executive 
functions, memory, language, visuoconstructional skills, conceptual thinking, 
calculations, and orientation [31].  This test is completed at baseline and Week 4.  
Different versions of the test are given at the two time points to avoid learning effects 
between repeated administrations of the test.  
 
Fatigability Questionnaire 
A self-administered, 26-item questionnaire to measure perceived mental and physical 
fatigability [32] is completed at baseline and Week 4.  
 
Short Form (SF) -12 Health Survey 
Self-administered, 12-item questionnaire to measure health-related quality of life is 
completed at baseline and Week 4.   
  
Anthropometric Measurements 
Body weight will be measured following the removal of excess clothing and shoes with 
calibrated scales.  
 
Waist circumference is taken at the mid-point between the participant’s lowest rib and 
the top of his/her hip bone. Both body weight and waist circumference measurements 
are completed at screening/baseline and Week 4.  
 
Activity Monitor 
A wrist activity monitor accelerometer to measure daily activity level is worn for the 
duration of the 4-week study intervention.  
 
Systemic Inflammatory biomarkers. Inflammatory biomarkers (CRP and IL-6) are 
measured by ELISA at Screening/Baseline and the Week 4 visit.  
 
Satisfaction Survey and Exit Interview 
At the conclusion of the study, participants are asked to complete a self-administered 
survey of their level of satisfaction and experience with his/her study participation.   
 
Participants will also complete an exit interview with study staff to allow sharing of 
additional feedback regarding study participation and the design of the full scale study 
protocol. 
 

 
 
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4.6 Statistical Analysis 
 
Sample size estimates for pilot studies are inherently difficult because by intent, a pilot 
study is meant to include a smaller sample than a fully powered study. The enrollment 
sample of 10 participants is intended to provide sufficient data to indicate feasibility of 
the intermittent fasting (i.e., time restricted feeding) intervention in this study population 
and to provide descriptive estimates of effects.    
 
Feasibility and acceptability of the proposed intervention in overweight, older adults will 
be evaluated by process variables including number of participants completing the 
study; adherence to study intervention, and number and severity of adverse events. We 
will also evaluate the participants’ responses on the satisfaction survey as part of the 
feasibility and acceptability assessment.    
 
4.7 Compensation 
For time and travel, participants will receive compensation of $25 for the 
Screening/Baseline clinic visit and $25 for the Week 4 follow-up clinic visit.  The 
maximum compensation for completing the study is $50. 
 
4.8 Data Safety Monitoring Plan and Data Safety Monitoring Board  
Data Safety Monitoring Plan 
 
Safety of the study participants is always our major concern. The study coordinator will 
record and monitor all adverse events reported at in person visits, and the study 
interventionist will record and monitor all adverse events reported by telephone. The 
Study Physician will determine the seriousness of any reported adverse events and 
whether or not the event is related to the study intervention.   
An adverse event is any untoward medical occurrence associated with the use of a 
drug in humans, whether or not considered study related. 
The event is serious if it results in death, is life-threatening, requires inpatient 
hospitalization or prolongs an existing hospitalization, results in a persistent or 
significant disability/incapacity, or congenital anomaly/birth defect.  
Safety related events are reported in a timely fashion, as required by the DSMB and the 
IRBs that are responsible for study oversight.  
The classification of potential relationship to the intervention is as follows. 
Definite - Temporal pattern + Known or expected AE response pattern + Confirmed by 
stopping the intervention + Reappearance of AE on re-challenge 
Possible - Temporal pattern + Known or expected AE response pattern + Could have 
been produced by a number of other factors 
Not related -  AE for which sufficient information exists to indicate that the cause is 

 
 
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unrelated to the study intervention 
Time to Eat study participants are comprised of an overweight, moderately functioning 
population expected to be at high risk for acute and chronic comorbid health events.  
A Data and Safety Monitoring Plan is implemented to ensure the safety of all 
participants involved in the study and to ensure the validity and integrity of the data. The 
Principal Investigator with the advice of the Study Physician monitor all aspects of 
safety.  
Data Safety Monitoring Board 
This project supported by the UF Claude D. Pepper Older Americans Independence 
Center (OAIC) grant (NIH P30 AG028740) and will utilize the OAIC Data Safety 
Monitoring Board (DSMB).  
The OAIC DSMB consists of an established board which has reviews all studies 
conducted within the UF OAIC. This board meets bi-annually and consists of the 
following individuals: (1) Stephen Kritchevsky, Ph.D., Chair, an epidemiologist who has 
been involved in research for many years, (2) Jing Cheng, Ph.D., a biostatistician who 
has been involved in numerous clinical trials, and (3) John Meuleman, M.D., a physician 
who has been involved in the conduct of clinical research for many years.  DSMB 
Reports will be provided to the UF IRB-01 with annual Continuing Review submissions. 
 
 
5. 
Possible Discomforts and Risks: 
Intermittent Fasting 
Only a limited number of human clinical trials have been published to date evaluating 
intermittent fasting dietary interventions [33, 34].  Of the adverse effects reported in 
these and other studies, undesirable weight loss and hunger were the two most 
prominent. It is likely that it will take participants several days to start adjusting to a time 
restricted eating pattern. During these times, participants may experience 
gastrointestinal discomfort, feelings of being more or less hungry than usual, and have 
more or less energy at certain times of the day than they usually have. While adhering 
to time restricted feeding, participants may feel their blood sugar levels fluctuate up and 
down more rapidly than they are typically used to, which may affect their energy levels 
and how hungry or full they feel. Also, there is a small risk that their blood sugar levels 
will go too high or too low. If their blood sugar levels drop too low, they may experience 
dizziness, sweating, sleepiness, anxiety, hunger, or weakness. Participants will be 
encouraged to contact the study physician and/or PI if they become concerned while 
adhering to this eating pattern.  
  
Risks associated with the blood draw. The risks of drawing blood from a vein include 
discomfort at the site of puncture; possible bruising and swelling around the puncture 
site; rarely an infection; and, uncommonly, faintness from the procedure. To minimize 
these risks, study staff are trained to properly draw blood and use measures that help 
prevent complications.  

 
 
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Risks associated with blood pressure measurement. The risks of placing a blood 
pressure cuff on a participant’s arms include pinching or slight bruising. To minimize 
these risks, study staff are trained to appropriately administer blood pressure tests.  
Risks associated with physical performance tests. There is a risk of losing balance and 
falling associated with the physical performance-based tested (e.g., 4 meter walk and 6 
minute walk tests). Falling includes the risk for bone fracture and soreness or injury to 
muscles or tendon/ligaments. To lessen these risks, participants will be safely escorted to 
chairs located along the walking course should he/she become unsteady. A Study 
Coordinator will follow at a close distance during the walking tests and will continuously 
monitor the participant for safety.   
The 6 minute walk test will be stopped immediately if any of the following signs and 
symptoms are reported or observed: chest pain, intolerable dyspnea, leg cramps, 
staggering, diaphoresis, and pale or ashen appearance.  
 
Risks associated with loss of confidentiality 
Lack of maintenance of confidentiality is a potential risk. Data are used only in 
aggregate and no identifying characteristics of individuals will be published or 
presented.  
 
Confidentiality of data is maintained by using research identification numbers that 
uniquely identify each individual. Safeguards are established to ensure the security and 
privacy of participants’ study records. Appropriate measures are taken to prevent 
unauthorized use of study information. The research ID number is used. The research 
records are kept in a limited access, secured storage area.  Only trained and certified 
study personnel has access to these files.  
 
In compliance with the Health Insurance Portability and Accountability Act (HIPAA) and 
the Standards for Privacy of Individually Identifiable Health Information of the 
Department of Health and Human Services, we access personal health information and 
medical records only after receiving signed informed consent. 
 
 
6. 
Possible Benefits: 
 
All study participants will take part in the intermittent fasting study intervention (time 
restricted feeding), which may or may not result in various health benefits.  
 
 
7. 
Conflict of Interest: 
 
None 
 
 
 
 
 

 
 
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