Clinical trial NCT02523274
Conditions: Aging
Sponsor: University of Florida
Start date: 2016-06-01; Completion date: 2019-07-17
Enrollment: 60 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this research study is to evaluate the effects of combining physical exercise with a resveratrol supplementation on the physical function of older adults.

Detailed description:
This investigation is a pilot study to investigate the potential of resveratrol, a commercially-available nutritional product, to enhance the efficacy of physical exercise in improving physical function among older adults with functional limitations. The overarching objective of this project is to evaluate the safety and efficacy of an intervention combining resveratrol supplementation and physical exercise among sedentary persons aged \> 65 years objectively-measured functional impairments. A total of 60 participants will be recruited to participate in this three month intervention study. All participants will engage in a center-based exercise program 3/days per week and will be randomly assigned to consume 1) placebo, 2) 500 mg/day resveratrol, or 3) 1000 mg/day resveratrol. This study will provide critical information regarding the influence of the combination of resveratrol and exercise on objectively-measured and self-assessed indices of physical function. The study will also provide novel biologic information regarding the relative effects of the interventions on skeletal muscle mitochondrial function.

Arms: arm 1: Placebo capsules will be taken orally daily in combination with exercise arm 2: 500 mg/day resveratrol taken orally in combination with exercise arm 3: 1000 mg/day resveratrol taken orally in combination with exercise
Interventions: intervention 1: Resveratrol intervention 2: Placebo intervention 3: Exercise
Intervention descriptions: intervention 1: Dietary compound commonly found in grapes and red wine. Will be given in 250 mg/day and 1000 mg/day dosages intervention 2: Vegetable-based cellulose intervention 3: Multi-modal exercise regimen, 3 days/week

Protocol documents:
Prot_SAP_000.pdf: 
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Protocol 
1. Project Title: 
Resveratrol and Exercise to Treat Functional Limitations in Late Life (RESTORES) 
2. Investigators: 
Thomas Buford, PhD 
Stephen Anton, PhD 
Christiaan Leeuwenburgh, PhD 
Marco Pahor, MD 
Bhanuprasad Sandesara, MD 
Samuel Wu, PhD 
3. Abstract:   
With persons aged ≥ 65 years representing the fastest growing segment of the U.S. population, the 
prevention of age-related functional decline and disability is an important public health priority. The loss of 
functional abilities in advanced age is associated with not only the onset of disability and the loss of 
independence but also with increased rates of morbidity and mortality. To date, physical exercise is the 
only intervention consistently demonstrated to improve physical function among older adults and is 
increasingly being considered the standard of cared for treating functional limitations. However, significant 
variability exists in responsiveness to exercise. As such, many individuals do not achieve clinically-
significant improvements in function despite good adherence. Accordingly, there is a need to identify 
adjuvant therapies capable of improving the efficacy of exercise in treating older adults with functional 
impairments. This project is a pilot study to investigate the potential of resveratrol, a commercially-
available nutritional product, to enhance the efficacy of physical exercise in improving physical function 
among older adults with functional limitations. The overarching objective of this project is to evaluate the 
safety and efficacy of an intervention combining resveratrol supplementation and physical exercise 
among sedentary persons aged 65 years objectively-measured functional limitations. A total of 60 
participants will be recruited to participate in this three month intervention study. All participants will 
engage in a center-based exercise program 2/days per week and will be randomly assigned to consume 
1) placebo, 2) 500 mg/day resveratrol, or 3) 1000 mg/day resveratrol. This study will provide critical 
information regarding the influence of the combination of resveratrol and exercise (REX) on objectively-
measured and self-assessed indices of physical function. The study will also provide biologic information 
regarding the relative effects of REX on skeletal muscle mitochondrial function.  
4. Background:  
The maintenance of one’s physical capabilities during older age is an essential part of healthy 
aging. Declines in physical abilities are associated with not only the onset of disability and the loss of 
independence but also with increased rates of morbidity and mortality.1-3 To date, physical exercise is 
the only intervention with consistent evidence supporting its use in treating age-related functional 
limitations. However, despite strong adherence to training, clinically-significant improvements in 
physical function are not obtained by many individuals.4,5 Thus exercise appears to be essential, but 
insufficient, for maintaining function among many seniors.6 Alternative strategies are therefore needed 
to improve the therapeutic efficacy of exercise in physically-limited older adults. Therefore, our long-
term goal is to develop interventions that optimize the efficacy of exercise as a strategy to prevent 
disablement among this high-risk population. 


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As our group has shown previously, skeletal muscle mitochondrial function declines with age and is 
a key factor in the maintenance of physical function among older adults.7,8 Moreover, several studies 
have demonstrated that mitochondrial adaptations to both acute and chronic exercise are attenuated in 
late life.9-12 Thus adjuvant therapies which stimulate mitochondrial function may hold promise for 
enhancing functional responses to exercise. Resveratrol, a polyphenol compound commonly found in 
the skin of red grapes, was previously suggested as a potential adjuvant to exercise due to its ability to 
stimulate mitochondrial biogenesis through peroxisome proliferator-activated receptor gamma co-
activator 1 alpha (PGC-1α) activity.13 In a recently completed pilot study, we observed that 12 weeks of 
resveratrol supplementation was well tolerated by overweight older adults and induced a dose-
dependent (300 vs. 1000 mg/day) increase in resting muscle oxidative metabolism. Additionally, 30 
days of resveratrol supplementation (150 mg/day) was recently reported to increase skeletal muscle 
mitochondrial function and PGC-1α content in obese, middle-aged men.14  
Subsequent studies using animal models of aging have reported that improvements in physical 
performance are greater in response to the combination of exercise and resveratrol than from either 
treatment alone.15-18 These studies overwhelmingly suggest that improvements in performance likely 
manifest as a result of enhanced skeletal muscle mitochondrial function. Thus, resveratrol appears to 
specifically target a key physiologic mechanism through which exercise improves physical function 
among older adults. We hypothesize that enhancing mitochondrial function may enhance physiologic 
adaptations to exercise such as aerobic fitness and skeletal muscle endurance. However, despite the 
promising findings from pre-clinical models, experimental data are sparse regarding the effects of this 
combined approach in humans. Consequently, well-controlled studies are needed to determine if the 
benefits of combining resveratrol with exercise demonstrated in pre-clinical studies can be translated to 
humans. Therefore, the purpose here, as the next step in pursuit of our long-term goal, is to evaluate 
the relative efficacy of combining physical exercise with oral resveratrol supplementation for improving 
the physical function of older adults at risk for disability.  
5. Specific Aims: 
The objective of this study is to conduct a pilot study to refine and finalize elements critical to 
conducting a future, definitive randomized, controlled trial (RCT). We propose to recruit 60 persons 
aged ≥ 65 years with functional limitations and follow them for 12 weeks. Participants will be randomly 
assigned to receive either (1) placebo plus 2 days/week of supervised, center-based, multi-modal 
exercise (EX), or (2) the same exercise program combined with either 500 or 1000 mg/day of 
resveratrol (REX). We will also collect skeletal muscle biopsies at baseline and 12 weeks from willing 
participants (i.e. optional for study participation) to evaluate skeletal muscle mitochondrial adaptations 
to the interventions. This study will enable us to address the following aims, all of which are of critical 
importance for designing a full-scale trial. 
1. To obtain critical data necessary to project the sample size needed for a full-scale trial using the 
change in 4m usual gait speed, a key predictor of health and survival in older adults,2,19,20 as the 
primary outcome. 
2. To determine the variance of secondary outcomes and short-term effects of the intervention on 
these outcomes, including: (1) exercise capacity, evaluated by distance walked during the 6-minute 
walk test, (2) lower-extremity function, assessed by the Short Physical Performance Battery 
(SPPB), (3) skeletal muscle strength and endurance, assessed by isokinetic muscle testing, and 4) 
self-assessed functional limitations, evaluated by the Late-Life Disability Questionnaire. 
3. To (a) assess the effects of resveratrol on exercise-induced changes in key indices of skeletal 
muscle mitochondrial function and quantity, and (b) determine the extent of association between 
changes in these mitochondrial outcomes and changes in measures of physical function.  


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6. Research Plan: 
 
We propose to conduct a randomized, controlled pilot trial to test that resveratrol improves functional 
responses of physically-limited older adults to chronic exercise training. Following study entry, participants 
(N = 60) will be randomly assigned to either EX or one of two REX groups for 12 weeks. Each condition 
will consist of two center-based resistance training sessions per week.  
 
6.1 Participants: Eligible participants will be males or females  ≥ 65 years of age with a sedentary lifestyle 
and objectively-measured functional limitations.  
 
Table 6.1. Inclusion and exclusion criteria 
Inclusion Criteria  
• 
Age 65 years  
• 
> 290 seconds needed to complete long-distance corridor walk test, as an indicator of functional 
limitation and moderate to low aerobic fitness3  
• 
Sedentary lifestyle, defined as <150 min/wk of moderate physical activity as assessed by 
CHAMPS questionnaire21 
• 
Willingness to be randomized to either treatment group 
• 
Willingness to participate in all study procedures 
Exclusion criteria  
• 
Failure to provide informed consent; 
• 
Regular consumption of a resveratrol supplement  
• 
Current involvement in supervised rehabilitation program  
• 
Absolute contraindication(s) to exercise training according to American College of Sports Medicine 
guidelines22 
• 
Pain classification > Grade 3 on Graded Chronic Pain Scale23  
• 
Peripheral vascular disease; peripheral neuropathy; retinopathy 
• 
Severe cardiac disease, including NYHA Class III or IV congestive heart failure, clinically 
significant aortic stenosis, history of cardiac arrest, use of a cardiac defibrillator, or uncontrolled 
angina;   
• 
Myocardial infarction or stroke within past year 
• 
Significant cognitive impairment, including known dementia diagnosis or a Mini-Mental State 
Examination exam score < 24  
• 
Progressive, degenerative neurologic disease, e.g., Parkinson’s Disease, multiple sclerosis, ALS; 
• 
Severe rheumatologic or orthopedic diseases, e.g., awaiting joint replacement, active inflammatory 
disease; 
• 
Severe pulmonary disease, requiring either steroid pills or injections or the use of supplemental 
oxygen; 
• 
Hip fracture, hip or knee replacement, or spinal surgery within past 4 mos.; 
• 
Other significant co-morbid conditions that would impair ability to participate in the exercise-based 
intervention 
• 
Simultaneous participation in another intervention trial 
 
FOR MUSCLE BIOPSY ONLY  
• 
Use of prescription anti-platelet medications (not including aspirin) 
• 
Prescription anti-coagulant use (e.g. warfarin) 
• 
Conditions which reduce wound healing, e.g. peripheral vascular disease, venous stasis 
• 
Known allergy to lidocaine 
 


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6.2 Recruitment: Participant recruitment will be coordinated in conjunction with the OAIC Clinical 
Research Core, led by co-investigator Dr. Stephen Anton. We will develop a targeted recruitment 
approach based on previous experiences utilizing methods of recruitment that include direct mailings, 
newspaper classified and print ads, community luncheons and health fairs, as well as clinic referrals. We 
have extremely successful in implementing this approach in past studies 
 
6.3 Screening and Study Entry: Interested individuals will initially complete a pre-screening interview by 
phone. Participants deemed eligible based on the pre-screening invited to an in-person screening visit. 
During this visit, potential participants will first be asked to give their informed consent and then will be 
screened for study entry criteria. Initial screening procedures will include a review of their medical history, 
physical activity habits, medication use, cognitive function (assessed by the Mini Mental State Exam), and 
a physical exam performed by a study physician. The study physician will review collected information 
relevant to potential participant’s health and make recommendation on this individual’s participation in this 
trial. 
Participants will then be asked to complete the long-distance corridor walk test to evaluate functional 
status and aerobic fitness. If all study entry criteria are met, participants will be scheduled to return to the 
clinic for baseline assessments. In addition, the study participants will be asked to sign Medical Records 
Release Authorization. This Authorization will be used exclusively to obtain medical records to acquire 
facts, details, and outcomes of Serious Adverse Events that occurred during the study and have to be 
reported to the sponsor and/or IRB. 
 
6.4 Baseline Assessment and Randomization: If all study entry criteria are met, participants will be 
scheduled to return to the clinic for baseline assessments prior to randomization. During this visit, 
participants will be asked to complete validated study questionnaires, including the Late-Life Disability 
Instrument24 and provide a fasting blood sample for evaluation of clinical safety lab values. Participants 
will also complete the Short Physical Performance Battery (SPPB), a 6-minute walk test, and 
assessments of muscle strength. Finally, the study coordinator will provide participants with an 
armband physical activity monitor and dietary intake form to take home to objectively evaluate baseline 
physical activity and dietary habits. Staff members will then discuss randomization procedures with 
participants. Participants who agree to participate in the muscle biopsy procedure will be scheduled for 
a separate visit prior to initiation of study interventions.  
 
6.5 Exercise Intervention: After random assignment to either the EX or the REX groups, participants will 
engage in a two days a week, center based resistance exercise intervention for 12 weeks. Following a 
brief warm-up, participants will be instructed to walk for 30 minutes at a 5-6 on the CR10 scale with 
encouragement for 10 minutes to be vigorous (7-8 on CR10 scale). Sessions will also include 30 
minutes of strength exercises for both lower- and upper-body followed by flexibility exercises and 
balance training to promote cool-down. Participants will be introduced to exercises in such a way that 
they begin with lighter intensity and gradually increase. The progressive nature of the intervention is 
designed to minimize discomfort and prevent injury. During the first week of the intervention, resistance 
exercises will be performed using lighter resistance where the focus will be on learning proper 
technique. Resistance training will be performed using standard isotonic resistance training equipment.  
 
Participants in the REX groups will be randomly assigned to receive, in a double-blind fashion, either 
500 or 1000 mg/day of encapsulated resveratrol or placebo. The company Reserveage Organics 
(Gainesville, FL) provided the resveratrol and placebo capsules for our previous study and will 
provide both the resveratrol and placebo capsules for the proposed study. Placebo capsules will be 
identical to those including resveratrol. Our 12-week resveratrol pilot study demonstrated that 
resveratrol supplementation at a dose of 1000 mg/day was safe and improved markers of 
metabolic function (i.e., blood glucose) in overweight, older adults. This dosage is also in line with 


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another recent pilot study by Crandall et al. (2012) which demonstrated safety and improvements 
in glucose metabolism and insulin sensitivity in older adults (mean age = 72 years) following 1000 
mg/day of resveratrol.25 The low dose has been previously shown to be sufficient for improving 
mitochondrial function3 and will allow for comparison with findings from the only human study of 
REX to our knowledge published to date.26,27   
 
Data from the exercise interventions will be collected and stored in the study database. Following each 
session, participants will be asked to provide a rating of perceived exertion (RPE) for the session 
according to the Borg CR10 scale. Additional data collected includes session attendance, 1 repetition 
maximum, and repetitions completed for each exercise per session.  
 
6.6 Adherence to interventions. To enhance adherence to the study interventions (compliance), we will 
utilize empirically-supported techniques which we have successfully utilized in prior studies. Our first 
step will to fully inform participants of study requirements before randomization and enroll only those 
persons who are willing to complete all study procedures. Undoubtedly, however, issues arise after 
randomization with the potential to limit compliance. Common causes of poor compliance include 
vacations, spouse care, fatigue, and fluctuations in motivation, perceived lack of benefit, physical 
discomfort, and adverse health experiences. First, we have designed the trial, including the 
inclusion/exclusion criteria and physician monitoring, to limit the likelihood of experiencing adverse 
health events in response to the interventions. In addition, care will be taken by the interventionists to 
promote the safe engagement in the exercise intervention. For other issues of non-compliance, we will 
approach this potential problem using a social problem solving model (“toolbox”) approach in dealing 
with individual adherence problems.28 This approach assumes that the process of changing behavior is 
a collaborative effort between the participant and the interventionists, and that behavior change can be 
readily undertaken during the regular weekly contacts that intervention staff will initiate throughout the 
course of the intervention, as well as during face-to-face visits. Our team has successfully applied this 
type of problem-solving approach in promoting adherence to behavioral interventions in prior studies. 
 
6.7 Follow-up and Close-out visits. In addition to baseline and screening visits, assessment visits will be 
conducted at 6 weeks (follow-up) and 12 weeks post-randomization. During the 6-week assessment 
visit, the research team will evaluate participant vital signs, collect blood samples, inquire about any 
adverse experiences since the last visit, and perform tests of physical performance evaluated 
performed at baseline. During the close-out (12 week) visit, the team will perform the same evaluations 
as during the 6-week visit, as well as administer study questionnaires, perform the SPPB, and collect 
home-based physical activity and dietary information from participants. Skeletal muscle biopsies will 
also be collected at 12 weeks from willing participants.  
 
6.8. Primary and Secondary Outcome Measures.  
Walking 
speed 
We will assess walking speed by asking the participants to walk at their usual pace 
over a 4 m course. Participants will be instructed to stand with both feet touching the 
starting line and to start walking after a specific verbal command. Timing will begin 
when the command is given, and the time needed to complete the entire distance will 
be recorded. The faster of two walks will be used. The reliability of the 4 m walk test is 
excellent – with an intraclass correlation coefficient (ICC) > 0.9.29  
Lower-
extremity 
function 
(SPPB) 
The SPPB is based on the 4m walk (above), repeated chair stands and a balance test. 
This test is reliable30 and valid for predicting institutionalization, hospital admission, 
mortality and disability.31,32-34 Each task is scored from 0 to 4, with 4 indicating best 
level of performance and 0 the inability to complete the test. A summary score (0-12) 
is then calculated. 


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6.9 Mitochondrial Outcome Measures.  
Measurement of skeletal muscle (1) in situ mitochondrial respiration, (2) proliferative activated receptor-
γ coactivator 1α (PGC-1α), (3) mitochondrial DNA, (4) citrate synthase (CS) activity, and (5) 
cytochrome C oxidase (COX) activity will be completed the OAIC Metabolism and Translational 
Science Core, led by co-investigator Dr. Christiaan Leeuwenburgh. Mitochondrial respiration will be 
determined immediately on freshly saponin-permeabilized muscle fibers as published previously8 using 
the high-resolution Oxygraph-2k (Oroboros, Innsbruck, Austria). Skeletal muscle PGC-1α, 
mitochondrial DNA content, as well as CS and COX activities will be determined using well-
standardized, validated methods with excellent test re-test reliability in the Core laboratory.42 
 
6.10 Sample size justification. This study will help generate precise estimates of effect variance in 
the population in which a subsequent larger-scale study will be conducted. Published 
recommendations for the design of pilot studies indicate that a sample of 15-20 participants per 
randomized arm is typically sufficient to estimate a parameter for a future trial.43-45 The enrollment 
sample of 60 participants is intended to provide preliminary data necessary to indicate feasibility of 
a larger trial and to provide descriptive estimates of effects. It will also provide for nominal 
estimation (using a 95% CI) of mean changes in dependent variables within each arm. While it is 
possible that statistically significant differences between arms may be observed, this pilot trial is not 
intended to be powered to observe such differences with high probability. For aims 1 and 2, assuming 
α = 0.05, we will have 80% power to detect an effect size of 0.74 for outcomes with three 
assessments (walking speed, muscle function, exercise capacity) and 0.79 for outcomes with two 
assessments (SPPB, self-assessed function, mitochondrial measurements), assuming a repeated 
measures correlation of 0.5. For the primary outcome of walking speed, we expect this detectable 
difference to be 0.12 m/sec based on a SD of 0.16 m/sec observed in the LIFE studies. For 
secondary aims, the following detectable effects sizes are expected based on our prior experience 
in LIFE and LIFE-P: SPPB, 1.3 points; 6-minute walk distance, 22.2 m; isokinetic peak torque, 27.8 
Nm; and Late Life Disability Instrument Score; 3.8 points.  
 
6.11 Safety monitoring plan. To ensure participant safety in the proposed study, we will adapt procedures 
that we have implemented successfully in other studies including LIFE,46,47 Weight Loss + Exercise,48 and 
Task Specific Exercise.49 As he has for a number of our prior studies, Dr. Bhanuprasad Sandesara will 
serve as the Study Physician who is responsible for assessment, monitoring and interventions for health 
events. To maximize participant safety we will follow a standardized screening protocol. Accordingly, all 
Skeletal 
muscle 
function 
Isokinetic strength and endurance of the knee flexors and extensors of the dominant 
limb will be assessed by a standard dynamometer as published previously.35,36  
Exercise 
capacity 
We will assess exercise capacity of participants using the six-minute (6-min) walk test, 
a safe and reliable test of aerobic endurance in older persons and those with 
cardiovascular conditions.37,38 This test has strong reproducibility, with intra-subject 
coefficients of variation averaging < 10%, and has a modest correlation with peak 
VO2.39 Participants will be asked to walk as far and fast as possible for 6-min on a 60 
m track. 
Self-
assessed 
physical 
function 
We will document self-assessed functional status using the Late Life Function and 
Disability Instrument.40,41 The instrument includes 16 tasks representing a broad range 
of disability indicators that assesses both frequency of doing a task and perceived 
limitation. The instrument uses a scale from 0 to 100, with higher scores indicating 
higher levels of function. The scale has strong concurrent and predictive validity with 
physical performance.24  


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potential participants will undergo screening for cardiovascular and other major diseases by means of a 
health questionnaire, medication inventory, and physical exam. Those with conditions that meet the 
exclusion criteria described in section 6.1 as determined by Dr. Sandesara will be excluded. Dr. 
Sandesara will also review clinically significant abnormal laboratory values and indicate the need for 
study withdrawal if he deems it necessary. Each participant will be instructed to report the occurrence of 
an adverse event at scheduled data collection times (scheduled clinical exams or phone interviews). 
Participants also have access to study clinic personnel at other times to report serious adverse events or 
concerns about the safety of participating in the study. If necessary, Release of Medical Records 
Authorizations signed by the study participants will be used to obtain medical records to collect details 
and outcomes of SAEs for safety and reporting purposes. 
Venipuncture will be performed by a trained and experienced phlebotomist using standard techniques. 
Participants will always have venipuncture performed while seated upright with both feet on the floor. 
Muscle biopsies will be performed by a licensed physician trained in the technique. A detailed description 
of the procedure is provided below. 
Muscle Biopsy Procedure – Vastus Lateralis 
• 
Participant should lie comfortably in a reclined position with both legs outstretched. Support can 
be added for calves/feet with pillows to maintain relaxed position 
• 
The participant is asked if they are allergic to latex, and if so, alternative material gloves must be 
used. 
• 
The muscle biopsy will be obtained approximately midway between the patella and iliac crest on 
the lateral thigh. See figure below. This distance was chosen so each participant will receive the 
biopsy at the same relative length of their lower extremity.  
 
• 
If necessary, an area of skin can be shaved to prevent hair from entering the incision and to 
improve adhesion of the sterile bandage 
• 
The skin is cleaned with an alcohol-based solution such as ChloraPrep® Swab, starting from 
the anticipated biopsy site in a circular motion extending to a diameter of approximately 4-5 
inches. 
• 
1 to 2 ml of 2% lidocaine is injected intradermally and subcutaneously. A brief period (i.e. 30-60 
seconds) allows for the skin to numb before injecting the remaining volume more deeply. The 
needle is inserted to just below the fascia, a small amount of lidocaine is injected starting below 
the fascia and injection is continued while the needle is drawn straight up through the 
subcutaneous tissue. This step is repeated in a star pattern.  
• 
8 to 10 minutes are allowed to pass after injection of the lidocaine before proceeding, to ensure 
maximal participant comfort. 
• 
Scalpel skin test: Using a blade scalpel, gently touch the scalpel to the anticipated site and ask 
the patient if they can feel anything where touched. It may help to have the patient close their 


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eyes. If they can feel the scalpel, allow more time and retest in 5 minutes. If the participant can 
still feel the blade touch, consider switching to carbocaine. 
• 
When the participant’s area of the leg is properly numbed, approximately 5 mm incision is made 
in the skin down through the muscle fascia.  The biopsy needle trocar is inserted through the 
incision, and through the fascia, advancing it into the muscle belly to obtain the muscle sample.  
If the yield is insufficient with study participant’s consent the trocar may re-inserted up to three 
times through the same hole in the fascia but at slightly different angles in the numbed area, as 
long as the participant is comfortable. 
• 
After completing the procedure, the study physician holds firm direct pressure over incision site 
for at least 5 minutes or longer until external bleeding has ceased. He/she then closes the 
incision with a sterile liquid bonding agent (such as Dermabond) or butterfly bandage. This will 
help prevent bleeding and scarring. Finally, the physician will apply a small amount of antibiotic 
and a sterile gauze pad over the incision and cover with a waterproof transparent dressing.  
The study participant will be provided with detailed instructions (discussion and a leaflet) on how to take 
care of the incision site. Study staff will make follow-up phone calls in the days following the procedure 
to monitor healing and any potential adverse events. 
Center-based assessments and interventions will be conducted and supervised by trained staff who will 
monitor potential adverse experiences and symptoms. All assessors and interventionists receive CPR 
training and training on management of acute events including syncope, chest pain, acute dyspnea, focal 
neurological symptoms and abnormal vital signs. Portable defibrillators are available at each intervention 
and assessment site and all study staff have on-call access to the study physician and contact numbers 
for emergency services are. Institutional and community EMS services will be activated if needed. As 
indicated previously, participants will be taught the importance and proper method of warming-up prior to 
and cooling-down following structured activity sessions. If at any point during an exercise session, 
participants develop chest pain, shortness of breath, or dizziness, they will be instructed to rest and to 
contact the center and their physicians if these symptoms persist or recur with further exercise.  
Blood pressure and heart rate will be measured before and after the resistance training at each center 
based session in participants who had experienced any of the following during a previous exercise 
session: decrease in diastolic blood pressure 20 mm Hg during the activity, increase in systolic blood 
pressure to 250 mm Hg or in diastolic blood pressure 115 mm Hg during the activity, increase in heart 
rate 90% of age predicted maximum, unusual or severe shortness of breath, chest pain or discomfort, 
palpitations, light headedness, dizziness or feeling about to faint, a session had to be discontinued 
because of other symptoms, excluding musculoskeletal symptoms (e.g., knees, ankles, hips), reported by 
the participant.  
 
Procedures to minimize discomfort include warm-up and cool-down activities that include cycling and 
flexibility exercises. The participants will also be introduced to the intervention exercises in a structured 
way, such that they begin with lighter resistance and gradually increase over the course of the first 2-3 
wks. During the intervention visits, participants will be supervised at all times and instructed on correct 
exercise techniques. Participants will also be instructed to move slowly when rising from a seated or lying 
position to reduce the risk of experiencing orthostatic hypotension. Study staff will be instructed to stand 
in a supportive position when participants are rising to prevent a fall in case of syncope. Participants will 
be instructed to talk with the interventionists about any muscle soreness. Exercise will be stopped if the 
participant reports pain, tightness or pressure in the chest, significant shortness of breath, feeling faint, 
lightheaded or dizzy, or significant other medical problems.  
Any significant adverse events will be reported promptly to the IRB and to the OAIC Data Safety 
Monitoring Board (DSMB). Otherwise, annual reports will be prepared for both. The OAIC DSMB 
consists of an established board which has reviewed all studies conducted within the University of 
Florida’s Pepper center during bi-annual conference calls for the past seven years. This board consists 


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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 
with a number of clinical trials, and (3) John Meuleman, M.D., a physician who has been involved in the 
conduct of clinical research for many years.   
Again, written informed consent will be obtained after explanation to subjects of all procedures and time 
commitments. The study interviewers will explain to prospective participants the purpose, methods and 
extent of the study. Potential participants will be asked to read the informed consent form and to ask 
questions. The form will be written in simple, easy-to-understand language. Staff members will also 
review all key aspects of the study verbally.  
Confidentiality of data will be maintained by using research identification numbers that uniquely identify 
each individual. Data will be used only in aggregate and no identifying characteristics of individuals will 
be published or presented. Safeguards will be established to ensure the security and privacy of 
participants’ study records. The information collected from participants in this study has a low potential 
for abuse, since the data do not address sensitive issues. Nevertheless, appropriate measures will be 
taken to prevent unauthorized use of study information. The research records will be kept in a locked 
room at the Institute on Aging. The files matching participants' names and demographic information 
with research ID numbers will be kept in a separate room and will be stored in a locked file that uses a 
different key from that of all other files. Only study personnel will have access to these files, and they 
will be asked to sign a document that they agree to maintain the confidentiality of the information. 
After the study is completed, local data will be stored with other completed research studies in a 
secured storage vault. 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 will access personal health information and medical records only 
after receiving signed informed consent, as described above.  
Finally, the study protocol will be registered at www.ClinicalTrials.gov before study enrollment begins. 
7. Possible Discomforts and Risks: 
Potential risks are those associated with health information privacy, venipuncture, muscle biopsies, and 
participation in exercise training and testing.  
Venipuncture can be associated with pain, bruising, hematoma formation, superficial phlebitis, and rarely 
cellulitis or fainting. The potential risks of the muscle biopsy procedure include infection, mild muscle 
soreness, scarring from the incision, mild nerve damage, swelling, and bleeding. The primary risk 
associated with moderate-intensity exercise training is skeletal muscle soreness. There are also other 
risks that relate to soft tissue injury, falls and fractures, exacerbation of arthritis and other joint conditions, 
post-exercise hypotension, and cardiovascular events.  There is a risk that a participant may trip, stumble, 
or fall during the physical performance tests and experience shortness of breath, dizziness, palpitations, 
chest pain or discomfort, heartburn, light headedness, or feeling about to faint. Strength training may 
involve a minimal risk of increasing intraocular and systemic pressures associated with use of the 
Valsalva maneuver to levels that may cause injury.  
8. Possible Benefits: 
Importantly, the proposed project should have tangible benefits for participants. These benefits include 
information about their health and assessments of their functional status. All study participants will be 
encouraged to communicate the results from the study to their primary care providers. Moreover, all 
participants – regardless of randomized group– will receive supervised exercise training and instruction 
about how to maintain exercise habits at home. We expect that these benefits will improve quality of life 
for all participants.    


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9. Conflict of Interest: 
Dr. Anton, a Sub-Investigator, is a paid adviser to Reserveage Organics that makes the 
resveratrol product that will be used in the study. 
 
 


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Literature Cited 
1. Shaw LJ, Olson MB, Kip K, Kelsey SF, Johnson BD, Mark DB, Reis SE, Mankad S, Rogers WJ, 
Pohost GM, Arant CB, Wessel TR, Chaitman BR, Sopko G, Handberg E, Pepine CJ, Bairey Merz CN. 
The value of estimated functional capacity in estimating outcome: results from the NHBLI-Sponsored 
Women's Ischemia Syndrome Evaluation (WISE) Study. J.Am.Coll.Cardiol. 2006; 47 (3 Suppl): S36-43. 
2. Studenski S, Perera S, Patel K, Rosano C, Faulkner K, Inzitari M, Brach J, Chandler J, Cawthon 
P, Connor EB, Nevitt M, Visser M, Kritchevsky S, Badinelli S, Harris T, Newman AB, Cauley J, Ferrucci 
L, Guralnik J. Gait speed and survival in older adults. JAMA 2011; 305 (1): 50-8. 
3. Newman AB, Simonsick EM, Naydeck BL, Boudreau RM, Kritchevsky SB, Nevitt MC, Pahor M, 
Satterfield S, Brach JS, Studenski SA, Harris TB. Association of long-distance corridor walk 
performance with mortality, cardiovascular disease, mobility limitation, and disability. JAMA 2006; 295 
(17): 2018-26. 
4. Manini TM, Newman AB, Fielding R, Blair SN, Perri MG, Anton SD, Goodpaster BC, Katula JA, 
Rejeski WJ, Kritchevsky SB, Hsu FC, Pahor M, LIFE Research Group. Effects of exercise on mobility in 
obese and nonobese older adults. Obesity (Silver Spring) 2010; 18 (6): 1168-75. 
5. Buford TW, Manini TM, Hsu FC, Cesari M, Anton SD, Nayfield S, Stafford RS, Church TS, 
Pahor M, Carter CS. Angiotensin-converting enzyme inhibitor use by older adults is associated with 
greater functional responses to exercise. J.Am.Geriatr.Soc. 2012; 60 (7): 1244-52. 
6. Keysor JJ and Brembs A. Exercise: necessary but not sufficient for improving function and 
preventing disability? Curr.Opin.Rheumatol. 2011; 23 (2): 211-8. 
7. Joseph AM, Adhihetty PJ, Buford TW, Wohlgemuth SE, Lees HA, Nguyen LM, Aranda JM, 
Sandesara BD, Pahor M, Manini TM, Marzetti E, Leeuwenburgh C. The impact of aging on 
mitochondrial function and biogenesis pathways in skeletal muscle of sedentary high- and low-
functioning elderly individuals. Aging Cell. 2012; 
8. Coen PM, Jubrias SA, Distefano G, Amati F, Mackey DC, Glynn NW, Manini TM, Wohlgemuth 
SE, Leeuwenburgh C, Cummings SR, Newman AB, Ferrucci L, Toledo FG, Shankland E, Conley KE, 
Goodpaster BH. Skeletal muscle mitochondrial energetics are associated with maximal aerobic 
capacity and walking speed in older adults. J.Gerontol.A Biol.Sci.Med.Sci. 2013; 68 (4): 447-55. 
9. Derbre F, Gomez-Cabrera MC, Nascimento AL, Sanchis-Gomar F, Martinez-Bello VE, 
Tresguerres JA, Fuentes T, Gratas-Delamarche A, Monsalve M, Vina J. Age associated low 
mitochondrial biogenesis may be explained by lack of response of PGC-1alpha to exercise training. 
Age (Dordr) 2012; 34 (3): 669-79. 
10. Toledo FG and Goodpaster BH. The role of weight loss and exercise in correcting skeletal 
muscle mitochondrial abnormalities in obesity, diabetes and aging. Mol.Cell.Endocrinol. 2013; 379 (1-
2): 30-4. 
11. Ljubicic V, Joseph AM, Saleem A, Uguccioni G, Collu-Marchese M, Lai RY, Nguyen LM, Hood 
DA. Transcriptional and post-transcriptional regulation of mitochondrial biogenesis in skeletal muscle: 
effects of exercise and aging. Biochim.Biophys.Acta 2010; 1800 (3): 223-34. 
12. Bori Z, Zhao Z, Koltai E, Fatouros IG, Jamurtas AZ, Douroudos II, Terzis G, Chatzinikolaou A, 
Sovatzidis A, Draganidis D, Boldogh I, Radak Z. The effects of aging, physical training, and a single 
bout of exercise on mitochondrial protein expression in human skeletal muscle. Exp.Gerontol. 2012; 47 
(6): 417-24. 
13. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne 
J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J. Resveratrol improves mitochondrial 
function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006; 127 
(6): 1109-22. 


Protocol RESTORES Study, IRB201500598 
Page 12 of 14 
IRB version 03.09.04 
PI version 09/15/2015 
14. Timmers S, Konings E, Bilet L, Houtkooper RH, van de Weijer T, Goossens GH, Hoeks J, van 
der Krieken S, Ryu D, Kersten S, Moonen-Kornips E, Hesselink MK, Kunz I, Schrauwen-Hinderling VB, 
Blaak EE, Auwerx J, Schrauwen P. Calorie restriction-like effects of 30 days of resveratrol 
supplementation on energy metabolism and metabolic profile in obese humans. Cell.Metab. 2011; 14 
(5): 612-22. 
15. Hart N, Sarga L, Csende Z, Koltai E, Koch LG, Britton SL, Davies KJ, Kouretas D, Wessner B, 
Radak Z. Resveratrol enhances exercise training responses in rats selectively bred for high running 
performance. Food Chem.Toxicol. 2013; 
16. Dolinsky VW, Jones KE, Sidhu RS, Haykowsky M, Czubryt MP, Gordon T, Dyck JR. 
Improvements in skeletal muscle strength and cardiac function induced by resveratrol during exercise 
training contribute to enhanced exercise performance in rats. J.Physiol. 2012; 590 (Pt 11): 2783-99. 
17. Menzies KJ, Singh K, Saleem A, Hood DA. Sirtuin 1-mediated Effects of Exercise and 
Resveratrol on Mitochondrial Biogenesis. J.Biol.Chem. 2013; 288 (10): 6968-79. 
18. Murase T, Haramizu S, Ota N, Hase T. Suppression of the aging-associated decline in physical 
performance by a combination of resveratrol intake and habitual exercise in senescence-accelerated 
mice. Biogerontology 2009; 10 (4): 423-34. 
19. Dumurgier J, Elbaz A, Ducimetiere P, Tavernier B, Alperovitch A, Tzourio C. Slow walking 
speed and cardiovascular death in well functioning older adults: prospective cohort study. BMJ 2009; 
339b4460. 
20. Afilalo J, Eisenberg MJ, Morin JF, Bergman H, Monette J, Noiseux N, Perrault LP, Alexander 
KP, Langlois Y, Dendukuri N, Chamoun P, Kasparian G, Robichaud S, Gharacholou SM, Boivin JF. 
Gait speed as an incremental predictor of mortality and major morbidity in elderly patients undergoing 
cardiac surgery. J.Am.Coll.Cardiol. 2010; 56 (20): 1668-76. 
21. Stewart AL, Mills KM, King AC, Haskell WL, Gillis D, Ritter PL. CHAMPS physical activity 
questionnaire for older adults: outcomes for interventions. Med.Sci.Sports Exerc. 2001; 33 (7): 1126-41. 
22. ACSM. ACSM's Guidelines for Exercise Testing and Prescription. 2006; 
23. Von Korff M, Ormel J, Keefe FJ, Dworkin SF. Grading the severity of chronic pain. Pain 1992; 
50 (2): 133-49. 
24. Sayers SP, Jette AM, Haley SM, Heeren TC, Guralnik JM, Fielding RA. Validation of the Late-
Life Function and Disability Instrument. J.Am.Geriatr.Soc. 2004; 52 (9): 1554-9. 
25. Crandall JP, Oram V, Trandafirescu G, Reid M, Kishore P, Hawkins M, Cohen HW, Barzilai N. 
Pilot study of resveratrol in older adults with impaired glucose tolerance. J.Gerontol.A Biol.Sci.Med.Sci. 
2012; 67 (12): 1307-12. 
26. Olesen J, Gliemann L, Bienso R, Schmidt J, Hellsten Y, Pilegaard H. Exercise training, but not 
resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men. J.Physiol. 
2014; 592 (Pt 8): 1873-86. 
27. Gliemann L, Schmidt JF, Olesen J, Bienso RS, Peronard SL, Grandjean SU, Mortensen SP, 
Nyberg M, Bangsbo J, Pilegaard H, Hellsten Y. Resveratrol Blunts the Positive Effects of Exercise 
Training on Cardiovascular Health in Aged Men. J.Physiol. 2013; 
28. Perri MG, Nezu AM, McKelvey WF, Shermer RL, Renjilian DA, Viegener BJ. Relapse 
prevention training and problem-solving therapy in the long-term management of obesity. 
J.Consult.Clin.Psychol. 2001; 69 (4): 722-6. 
29. Rolland YM, Cesari M, Miller ME, Penninx BW, Atkinson HH, Pahor M. Reliability of the 400-m 
usual-pace walk test as an assessment of mobility limitation in older adults. J.Am.Geriatr.Soc. 2004; 52 
(6): 972-6. 


Protocol RESTORES Study, IRB201500598 
Page 13 of 14 
IRB version 03.09.04 
PI version 09/15/2015 
30. Ostir GV, Volpato S, Fried LP, Chaves P, Guralnik JM, Women's Health and Aging Study. 
Reliability and sensitivity to change assessed for a summary measure of lower body function: results 
from the Women's Health and Aging Study. J.Clin.Epidemiol. 2002; 55 (9): 916-21. 
31. Penninx BW, Ferrucci L, Leveille SG, Rantanen T, Pahor M, Guralnik JM. Lower extremity 
performance in nondisabled older persons as a predictor of subsequent hospitalization. J.Gerontol.A 
Biol.Sci.Med.Sci. 2000; 55 (11): M691-7. 
32. Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace RB. Lower-extremity function in 
persons over the age of 70 years as a predictor of subsequent disability. N.Engl.J.Med. 1995; 332 (9): 
556-61. 
33. Perkowski LC, Stroup-Benham CA, Markides KS, Lichtenstein MJ, Angel RJ, Guralnik JM, 
Goodwin JS. Lower-extremity functioning in older Mexican Americans and its association with medical 
problems. J.Am.Geriatr.Soc. 1998; 46 (4): 411-8. 
34. Guralnik JM, Ferrucci L, Pieper CF, Leveille SG, Markides KS, Ostir GV, Studenski S, 
Berkman LF, Wallace RB. Lower extremity function and subsequent disability: consistency across 
studies, predictive models, and value of gait speed alone compared with the short physical 
performance battery. J.Gerontol.A Biol.Sci.Med.Sci. 2000; 55 (4): M221-31. 
35. Buford TW, Cooke MB, Manini TM, Leeuwenburgh C, Willoughby DS. Effects of Age and 
Sedentary Lifestyle on Skeletal Muscle NF-{kappa}B Signaling in Men. J.Gerontol.A Biol.Sci.Med.Sci. 
2010; 
36. Buford TW, Cooke MB, Redd LL, Hudson GM, Shelmadine BD, Willoughby DS. Protease 
Supplementation Improves Muscle Function after Eccentric Exercise. Med.Sci.Sports Exerc. 2009; 
37. Enright PL, McBurnie MA, Bittner V, Tracy RP, McNamara R, Arnold A, Newman AB, 
Cardiovascular Health Study. The 6-min walk test: a quick measure of functional status in elderly 
adults. Chest 2003; 123 (2): 387-98. 
38. Fleg JL, Pina IL, Balady GJ, Chaitman BR, Fletcher B, Lavie C, Limacher MC, Stein RA, 
Williams M, Bazzarre T. Assessment of functional capacity in clinical and research applications: An 
advisory from the Committee on Exercise, Rehabilitation, and Prevention, Council on Clinical 
Cardiology, American Heart Association. Circulation 2000; 102 (13): 1591-7. 
39. Steele B. Timed walking tests of exercise capacity in chronic cardiopulmonary illness. 
J.Cardiopulm.Rehabil. 1996; 16 (1): 25-33. 
40. Jette AM, Haley SM, Coster WJ, Kooyoomjian JT, Levenson S, Heeren T, Ashba J. Late life 
function and disability instrument: I. Development and evaluation of the disability component. 
J.Gerontol.A Biol.Sci.Med.Sci. 2002; 57 (4): M209-16. 
41. Haley SM, Jette AM, Coster WJ, Kooyoomjian JT, Levenson S, Heeren T, Ashba J. Late Life 
Function and Disability Instrument: II. Development and evaluation of the function component. 
J.Gerontol.A Biol.Sci.Med.Sci. 2002; 57 (4): M217-22. 
42. Joseph AM, Ljubicic V, Adhihetty PJ, Hood DA. Biogenesis of the mitochondrial Tom40 
channel in skeletal muscle from aged animals and its adaptability to chronic contractile activity. 
Am.J.Physiol.Cell.Physiol. 2010; 298 (6): C1308-14. 
43. Lancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: recommendations 
for good practice. J.Eval.Clin.Pract. 2004; 10 (2): 307-12. 
44. Browne RH. On the use of a pilot sample for sample size determination. Stat.Med. 1995; 14 
(17): 1933-40. 
45. Hertzog MA. Considerations in determining sample size for pilot studies. Res.Nurs.Health 
2008; 31 (2): 180-91. 
46. LIFE Study Investigators, Pahor M, Blair SN, Espeland M, Fielding R, Gill TM, Guralnik JM, 
Hadley EC, King AC, Kritchevsky SB, Maraldi C, Miller ME, Newman AB, Rejeski WJ, Romashkan S, 


Protocol RESTORES Study, IRB201500598 
Page 14 of 14 
IRB version 03.09.04 
PI version 09/15/2015 
Studenski S. Effects of a physical activity intervention on measures of physical performance: Results of 
the lifestyle interventions and independence for Elders Pilot (LIFE-P) study. J.Gerontol.A 
Biol.Sci.Med.Sci. 2006; 61 (11): 1157-65. 
47. Fielding RA, Rejeski WJ, Blair S, Church T, Espeland MA, Gill TM, Guralnik JM, Hsu FC, 
Katula J, King AC, Kritchevsky SB, McDermott MM, Miller ME, Nayfield S, Newman AB, Williamson JD, 
Bonds D, Romashkan S, Hadley E, Pahor M, for the LIFE Research Group. The Lifestyle Interventions 
and Independence for Elders Study: Design and Methods. J.Gerontol.A Biol.Sci.Med.Sci. 2011; 
48. Anton SD, Manini TM, Milsom VA, Dubyak P, Cesari M, Cheng J, Daniels MJ, Marsiske M, 
Pahor M, Leeuwenburgh C, Perri MG. Effects of a weight loss plus exercise program on physical 
function in overweight, older women: a randomized controlled trial. Clin.Interv.Aging 2011; 6141-9. 
49. Naugle KM, Higgins TJ, Manini TM. Obesity and use of compensatory strategies to perform 
common daily activities in pre-clinically disabled older adults. Arch.Gerontol.Geriatr. 2012; 54 (2): e134-
8. 
 
  
 

ICF_001.pdf: 
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INFORMED CONSENT FORM
to Participate in Research, and
AUTHORIZATION 
to Collect, Use, and Disclose Protected 
Health Information (PHI)
INTRODUCTION
Name of person seeking your consent:
Place of employment & position: 
Please read this form which describes the study in some detail. A member of the 
research team will describe this study to you and answer all of your questions.  Your 
participation is entirely voluntary.  If you choose to participate you can change your mind 
at any time and withdraw from the study.  You will not be penalized in any way or lose any 
benefits to which you would otherwise be entitled if you choose not to participate in this 
study or to withdraw.  If you have questions about your rights as a research subject, 
please call the University of Florida Institutional Review Board (IRB) office at (352) 273-
9600.   
GENERAL INFORMATION ABOUT THIS STUDY
1.
Name of Participant ("Study Subject")
___________________________________________________________________ 
2.
What is the Title of this research study?
Resveratrol and Exercise to Treat Functional Limitations in Late Life (RESTORES)
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3.
Who do you call if you have questions about this research study?
Principal Investigator: Thomas W. Buford, 352-273-9212
Study coordinators and other research staff:  352-273-9212
Medical safety officer: Bhanuprasad Sandesara, MD, 352-413-0592 (pager, 24 h)
4.  Who is paying for this research study? 
The proposed sponsor of this study is the National Institute on Aging.  A private 
company, Reserveage Organics, is providing nutritional supplement (resveratrol and 
placebo) for this research study.
5. Why is this research study being done? 
The purpose of this research study is to evaluate the effects of combining physical 
exercise with a resveratrol supplementation on the physical function of older adults.
You are being asked to be in this study because you are over 65 years of age.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law.  This Web site will not include information that can identify you. 
 At most, the Web site will include a summary of the results. You can search this Web 
site at any time.
WHAT CAN YOU EXPECT IF YOU PARTICIPATE IN THIS STUDY?
6.  What will be done as part of your normal clinical care (even if you did not 
participate in this research study)? 
No procedures in this study will be part of your normal clinical care.
7.  What will be done only because you are in this research study? 
An initial telephone screening indicated that you may be eligible to participate in the 
study. The first study visit (“Screening visit”) will further determine if you are eligible to 
participate. Should you be eligible to participate in the study, you will be asked to 
participate in a structured physical activity program for 12 weeks as well as consume 
the nutritional supplements provided to you. You will also be asked to return to the 
clinic for several additional assessment visits to monitor your safety and measure 
study results.
This exercise program includes: walking, lower-body and upper-body strengthening, 
flexibility, and balance training. You will be asked to attend two physical activity 
sessions per week for 12 weeks at our physical activity center. These sessions will be 
led by our study staff and will introduce you to exercise parts of the program in a safe 
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manner. To reduce any chances of injury, exercises will be light at first and will slowly 
increase in difficulty. This will allow the study staff to tailor the program to your 
individual needs and abilities.
You will be randomly assigned (like flipping a coin) into one of three groups: exercise 
and lower-dose resveratrol, exercise and higher-dose resveratrol, or exercise and 
placebo (an identically appearing pill containing no resveratrol). Resveratrol is a 
compound commonly found in the skin of red grapes with reported beneficial health 
effects. You will be asked to consume your provided supplementation daily. You will 
not know which supplement you are taking. 
If you wish to participate, your first visit will be to determine your eligibility for the 
study. Details regarding the tests to be conducted during this screening visit and other 
study visits (if you are eligible) are described below. Visits will take place at the 
University of Florida Institute on Aging (IOA), and the physical activity program will 
take place at the IOA Health Promotion Center.
Screening Visit: The screening visit is expected to take 1 to 2 hours. Details of study 
procedures that will be conducted during this visit are below. The order of these 
procedures may vary based on the schedules of study staff.
Written Consent
Before any tests or procedures are performed, you will be asked to give written 
consent to participate in this research study. The study team member will explain in 
detail what is involved in the study and you will be given the opportunity to ask and 
have answered any questions. If you decide that you would like to participate in the 
study we will ask you to sign this consent form.
Questionnaires
You will be asked questions about your medical history as well as your physical 
activity habits. You will also be asked to complete a short test of memory and 
reasoning.
Physical Measurements and Exam
We will take measurements of your height, body weight, pulse, and blood pressure. A 
medical professional will also give you a short physical exam to determine if it is safe 
for you to participate in the study.
Tests of physical performance
You will be asked to complete a test of your physical ability. The test will include being 
asked to walk at a fast pace for a distance of 400 meters (1312 feet). 
Medical records release authorization
The study team will ask you to sign the Medical Records Release Authorization. We 
would like to have this form signed by you if we need to request your health records if 
you are hospitalized or any health problems worsen and the study team has to report 
details of these events to regulatory authorities (Institutional Review Board, the study 
sponsor, etc.) to ensure your safety during participation in this research study. This 
form will be signed only once – during the Screening Visit. Health information 
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collected using this release will be used only for any health events that occur during 
your participation in this research.
At the end of this visit, the study team will determine if you can participate in this 
study. If you are not eligible, this will be your only study visit. 
Baseline Visit: Should you be eligible for the study, you will be asked to return to the 
clinic for the baseline study visit. This visit is expected to take 2 to 3 hours and will 
include:
Physical measurements
We will take measurements of your height, body weight, pulse, and blood pressure.
Blood Draw
You will be asked to fast before your appointment because blood will be collected 
during this visit.  We will provide a snack for you before you continue with your visit 
procedures, after we draw your blood. We will collect approximately 2 tablespoons of 
blood from a small vein in your arm or hand.  The purpose of this blood draw is to 
determine levels of certain compounds in your blood that will help us determine  some 
details of your health  and study eligibility. Should you remain eligible after completing 
the rest of the screening battery, you will be called to inform you of your eligibility 
status based on these tests. 
Questionnaires
You will be asked questions about your overall health – including questions about pain 
and your perception of your physical abilities. 
Physical Performance Tests
You will be asked to complete tests of your physical ability. You will perform tests of 
your physical ability that include: 
1. You will be asked to walk at your usual pace for a distance of 13 feet (4 meters) 
two (2) separate times
2. You will be asked to stand from sitting position, without using your arms. If you 
are able to perform this task, you will be to stand up from and sit down on chair 
five (5) times as fast you as can
3. You will be asked to maintain your balance while standing in three (3) different 
positions, 1) with your feet together, 2) with the heel of one beside the big toe of 
the other foot, and 3) the heel of one foot in front of and touching the toes of the 
other foot
4. You will be asked to walk as far as you can for a duration of 6 minutes
Assessment of lower-body muscle strength
You will be asked to perform a test which requires pushing your leg against a 
machine which pushes against you to measure the strength of your leg muscles. 
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You will also be provided with your nutritional supplement (Resveratrol or placebo) to 
be taken orally until your next appointment. 
Additionally, you will be provided with an armband physical activity monitor to wear for 
approximately seven (7) days and provided instructions for its use as well as a dietary 
assessment form with instructions for completing it.   
Optional Study Visits
You will be also asked if you would like to participate in additional study visits. These 
visits are described in a separate consent form that you will be asked to sign if you 
decide take part in these optional study visits.
6 Week Visit: This visit is expected to take 1 to 2 hours and will include: 
Measurement of pulse and blood pressure
Collection of another blood sample after you have fasted the evening before
Questions about any adverse experiences since last visit
Performing 6 minute walk test
Perform test of lower-body muscle strength
You will also be provided with your nutritional supplement (Resveratrol or placebo)  
to take until your next appointment
We will collect dietary assessment questionnaire you were given during your last 
study visit
12 Week (close-out) Visit: This will be the final study visit. It is expected to take 2 to 
3 hours and will include:
Measurement of pulse and blood pressure
Collection of another blood sample after you have fasted the evening before
Questions about any adverse experiences since last visit
Questions about your perception of your physical abilities (as during baseline visit)
Questions about your health (as during baseline visit)
Perform tests of physical performance and strength (as during baseline visit)
We will collect physical activity monitor that was provided to you for use at home
If you have any questions now or at any time during the study, please contact one of 
the research team members listed in question 3 of this form.
During your study visit, the study team will ask you to report serious health events that 
occurred to you since you last assessment visit. If more details about the event are 
required, the study team will use Medical Records Release Authorization that you 
signed at the Screening visit. Information collected will pertain only to this particular 
medical event.
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8.
How long will you be in this research study?
If you qualify for the study, your expected participation in the study is approximately 
three to four months – though it may be slightly longer if conflicts arise in scheduling 
of assessment visits. 
9.
How many people are expected to take part in this research study?
We expect approximately 60 people to pass screening and participate in the study.
WHAT ARE THE RISKS AND BENEFITS OF THIS STUDY AND 
WHAT ARE YOUR OPTIONS?
10. What are the possible discomforts and risks from taking part in this research 
study?
There are some possible discomforts and risks associated with participating in the 
study.  
The potential risks associated with resveratrol supplementation are not fully known at 
the present time. Resveratrol is similar to the synthetic estrogen and may have 
estrogenic activity. Resveratrol might also interact with blood thinners such as 
warfarin, and non-steroidal, anti-inflammatory medications, thereby increasing the risk 
for bleeding. Adverse effects of resveratrol have not been reported at doses of 1000 
mg/day, 1500 mg/day and 2000 mg/day; however, long-term side effects are not 
known. In our resveratrol pilot study which was conducted on older adults, resveratrol 
supplementation at doses of 300 mg/day and 1000 mg/day had minimal effects on 
results of blood tests of older adults, and there were no big differences in the number 
of participants reporting adverse or side effects (e.g. headaches) between group 
taking 300 mg or 1000 mg of resveratrol a day.
There is a risk of losing your balance and falling associated with the physical 
performance-based testing (e.g., walking and rising from a chair). A fall also places 
you at risk of a bone fracture. We will minimize this risk by: (1) safely escorting you to 
chairs located along the walking course should you become unsteady; (2) following 
you at a close distance; and, (3) being at your side should you need assistance.
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. 
There may be some discomfort in the beginning of the study from increasing your 
physical activity.  The possibilities include, but are not limited to, some muscle and 
joint stiffness.  This stiffness generally subsides in 1 or 2 days, and is not considered 
to be serious.  You might experience an exercise-related injury such as a strain, 
sprain, or other injury to your muscles or joints. Other possible adverse physical 
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responses include abnormal blood pressure, fainting, abnormal heart beats, and, in 
rare instances, heart attack, stroke, and death.  Every effort is made to minimize 
these risks by reviewing information about your health before the activities begin.  We 
will minimize these by showing you how to properly do the exercises in a safe manner 
and performing warm-up and cool-down exercises.  We will also monitor heart rate 
and blood pressure before and after your exercise sessions. You will also be 
encouraged to report and discuss any discomforts with members of the study staff.  
Taking part in this research may involve providing information that you consider 
confidential or private. Efforts such as coding research records, keeping research 
records secure and allowing only authorized people to have access to research 
records, will be made to keep your information safe.
Researchers will take appropriate steps to protect any information they collect about 
you.  However, there is a slight risk that information about you could be revealed 
inappropriately or accidentally.  Depending on the nature of the information, such a 
release could upset or embarrass you, or possibly affect your insurability or 
employability.  Questions 17-21 in this form discuss what information about you will 
be collected, used, protected, and shared.
This study may include risks that are unknown at this time.
Participation in more than one research study or project may further increase the risks 
to you.  If you are already enrolled in another research study, please inform one of the 
research team members listed in question 3 of this form or the person reviewing this 
consent with you before enrolling in this or any other research study or project.
Throughout the study, the researchers will notify you of new information that may 
become available and might affect your decision to remain in the study. 
If you wish to discuss the information above or any discomforts you may experience, 
please ask questions now or call one of the research team members listed in question 
3 in this form.
11a. What are the potential benefits to you for taking part in this research study?
Potential benefits of this study to you include learning information about your health 
and overall physical function. Also, you will have the opportunity to receive supervised 
exercise training and instruction about how to maintain physical activity habits at 
home. Participation in these activities has the potential to improve your health and 
quality of life. 
11b. How could others possibly benefit from this study?
Information gained from participation in this study may help to provide doctors with 
new information for recommending exercise treatments. The study may also provide 
scientists and physicians with new knowledge about the use of resveratrol and 
potential beneficial effects when combined with exercise. 
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11c. How could the researchers benefit from this study?
In general, presenting research results helps the career of a scientist. Therefore, the 
Principal Investigator listed in question 3 of this form may benefit if the results of this 
study are presented at scientific meetings or in scientific journals.
Dr. Anton, a Sub-Investigator, is a paid adviser to Reserveage Organics that makes 
the resveratrol product that will be used in the study. Please feel free to ask any 
questions you may have about this matter. 
12. What other choices do you have if you do not want to be in this study? 
If you do not wish to be in this study, please tell a study team member and do not sign 
this form. 
13a. Can you withdraw from this study?
You are free to withdraw your consent and to stop participating in this study at any 
time.  If you do withdraw your consent, you will not be penalized in any way and you 
will not lose any benefits to which you are entitled.  If you decide to withdraw your 
consent to participate in this study for any reason, please contact one of the research 
team members listed in question 3 of this form. They will tell you how to stop your 
participation safely.
If you have any questions regarding your rights as a research subject, please call the 
Institutional Review Board (IRB) office at (352) 273-9600.
13b.If you withdraw, can information about you still be used and/or collected?
If you withdraw, no further information will be collected. Information already collected 
from you may be used in final data analyses.
13c. Can the Principal Investigator withdraw you from this study? 
You may be withdrawn from the study without your consent for the following reasons:

The Principal Investigator feels it is necessary for your health or safety. You will be 
informed if this decision is made and the reason for this decision.

New information suggests that taking part in the research study may not be in your 
best interests.

The sponsor or the Principal Investigator has decided to stop the study for any 
other reason. 
You may also be withdrawn from the study if you do not follow the instructions given to 
you by the Principal Investigator or the study team.
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WHAT ARE THE FINANCIAL ISSUES IF YOU PARTICIPATE?
14. If you choose to take part in this research study, will it cost you anything?
Study Drugs and Devices
Resveratrol or placebo, Lidocaine for Muscle Biopsy Procedure (as needed), and the 
Accelerometer will be provided at no cost to you while you participating in this study.
Study Sercives
The Sponsor will pay for all  services  required as part of your participation in this 
study as described above in the question “What Will Be Done Only Because You 
Are In This Research Study”. If you receive a bill for these services, please contact 
Dr Buford at 352-273-5918 or the study coordinator at 352-273-9212.
Any other medical services provided to you that are not directly required by this   
study will be billed to you or your insurance company in the usual manner. 
15. Will you be paid for taking part in this study?
Yes, you will be compensated up to $115 in the form of gift cards. A gift card in the 
amount of $25 will be given at the completion of the screening visit. If you are eligible 
and choose to participate, gift cards in the amount of $30 will be given upon 
completion of each additional study assessment visit. You will not be compensated for 
attending the study physical activity program. However, we may provide 
transportation or transportation assistance for attending the physical activity program 
should you need it. 
Participants may qualify for this travel assistance based on the following criteria:
1. Not having transportation to attend intervention sessions
2. Medical condition which prohibits driving and other forms of transportation not 
available
3. Financial issues associated with cost of transportation
4. Unique situation (these will be discussed with team prior to status determination)
Travel assistance may also be possible if attending assessment visits from a 
significant distance. If you need and think you may qualify for travel reimbursement, 
you should speak to a member of the study team about this possibility. The team 
member will discuss this possibility with you and ask to sign a form indicating that you 
understand the type of reimbursement and criteria for continuing to qualify for the 
assistance. 
16. What if you are injured because of the study?  
If you are injured as a direct result of your participation in this study, only the 
professional services that you receive from any University of Florida Health Science 
Center healthcare provider will be provided without charge.  These healthcare 
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providers include physicians, physician assistants, nurse practitioners, dentists or 
psychologists. Any other expenses, including Shands hospital expenses, will be billed 
to you or your insurance provider. 
You will be responsible for any deductible, co-insurance, or co-payments. Some 
insurance companies may not cover costs associated with research studies or 
research-related injuries. Please contact your insurance company for additional 
information. 
The Principal Investigator will determine whether your injury is related to your 
participation in this study. 
No additional compensation is offered. The Principal Investigator and others involved 
in this study may be University of Florida employees. As employees of the University, 
they are protected under state law, which limits financial recovery for negligence.
Please contact one of the research team members listed in question 3 of this form if 
you experience an injury or have questions about any discomforts that you 
experience while participating in this study.
17. How will your health information be collected, used and shared?
If you agree to participate in this study, the Principal Investigator will create, collect, 
and use private information about you and your health. This information is called 
protected health information (PHI). In order to do this, the Principal Investigator needs 
your authorization  The following section describes what PHI will be collected, used 
and shared, how it will be collected, used, and shared, who will collect, use or share 
it, who will have access to it, how it will be secured, and what your rights are to revoke 
this authorization. 
Your protected health information may be collected, used, and shared with others to 
determine if you can participate in the study, and then as part of your participation in 
the study.  This information can be gathered from you or your past, current or future 
health records, from procedures such as physical examinations, x-rays, blood or urine 
tests or from other procedures or tests.  This information will be created by receiving 
study treatments or participating in study procedures, or from your study visits and 
telephone calls.  More specifically, the following information may be collected, used, 
and shared with others: 
First and last name
Contact information
Date of birth
Social security number for compensation 
Information about your health status such as weight and height
Complete past medical history to determine eligibility criteria
Laboratory test results 
Answers to health questionnaires
Answers to cognitive abilities questionnaires
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Physical performance test results
This information will be stored in locked filing cabinets or on computer servers with 
secure passwords, or encrypted electronic storage devices. 
Some of the information collected could be included in a "limited data set" to be used 
for other research purposes.  If so, the limited data set will only include information 
that does not directly identify you.  For example, the limited data set cannot include 
your name, address, telephone number, social security number, photographs, or 
other codes that link you to the information in the limited data set.  If limited data sets 
are created and used, agreements between the parties creating and receiving the 
limited data set are required in order to protect your identity and confidentiality and 
privacy.
18.  For what study-related purposes will your protected health information be 
collected, used, and shared with others?
Your PHI may be collected, used, and shared with others to make sure you can 
participate in the research, through your participation in the research, and to evaluate 
the results of the research study.  More specifically, your PHI may be collected, used, 
and shared with others for the following study-related purpose(s):
To determine if you are eligible for the study.
To determine if changes in health and well-being in response to exercise depend on 
the type of nutritional supplement taken.
Once this information is collected, it becomes part of the research record for this 
study.  
19.  Who will be allowed to collect, use, and share your protected health 
information?
Only certain people have the legal right to collect, use and share your research 
records, and they will protect the privacy and security of these records to the extent 
the law allows. These people include:
the study Principal Investigator (listed in question 3 of this form) and research staff 
associated with this project.
other professionals at the University of Florida or Shands Hospital that provide study-
related treatment or procedures.
the University of Florida Institutional Review Board (IRB; an IRB is a group of people 
who are responsible for looking after the rights and welfare of people taking part in 
research).  
20.  Once collected or used, who may your protected health information be shared 
with?
Your PHI may be shared with:
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the study sponsor (listed in Question 4 of this form).
United States governmental agencies who are responsible for overseeing research. 
Otherwise, your research records will not be released without your permission unless 
required by law or a court order. It is possible that once this information is shared with 
authorized persons, it could be shared by the persons or agencies who receive it and 
it would no longer be protected by the federal medical privacy law.  
21.  If you agree to take part in this research study, how long will your protected 
health information be used and shared with others?
Your PHI will be used and shared with others until the end of the study, which is the 
time when the study has been closed with University of Florida’s IRB.
You are not required to sign this consent and authorization or allow researchers to 
collect, use and share your PHI. Your refusal to sign will not affect your treatment, 
payment, enrollment, or eligibility for any benefits outside this research study. 
However, you cannot participate in this research unless you allow the collection, use 
and sharing of your protected health information by signing this consent and 
authorization.
You have the right to review and copy your protected health information.  However, 
we can make this available only after the study is finished.
You can revoke your authorization at any time before, during, or after your 
participation in this study.  If you revoke it, no new information will be collected about 
you.  However, information that was already collected may still be used and shared 
with others if the researchers have relied on it to complete the research.  You can 
revoke your authorization by giving a written request with your signature on it to the 
Principal Investigator.
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SIGNATURES
As an investigator or the investigator’s representative, I have explained to the participant 
the purpose, the procedures, the possible benefits, and the risks of this research study; 
the alternative to being in the study; and how the participant’s protected health 
information will be collected, used, and shared with others: 
Signature of Person Obtaining Consent and 
Authorization
Date
You have been informed about this study’s purpose, procedures, possible benefits, and 
risks; the alternatives to being in the study; and how your protected health information will 
be collected, used and shared with others.  You have received a copy of this Form.  You 
have been given the opportunity to ask questions before you sign, and you have been 
told that you can ask   questions at any time.  
You voluntarily agree to participate in this study. You hereby authorize the collection, use 
and sharing of your protected health information as described in sections 17-21 above.  
By signing this form, you are not waiving any of your legal rights.
Signature of Person Consenting and Authorizing
Date
 
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