The Fuel and Rhythm (FAR) Phase 2 Study

Aging Clinical Trial

Official title:

Assessment of Fuel Utilization and Circadian Rhythms in Overweight, Older Adults Following Time Restricted Eating - Phase 2 (FAR Phase 2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05482711
• Other study ID #: IRB202102618 -N
• Secondary ID: P30AG028740
• Status: Recruiting
• Phase: N/A
• Start date: January 10, 2023
• Est. completion date: March 31, 2026

Study information

• Verified date: January 2024
• Source: University of Florida
• Contact: Stephen Anton, Ph.D.
• Phone: 352-273-7514
• Email: santon[@]ufl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Both fuel metabolism and circadian rhythms have emerged as important targets to improve cellular and mitochondrial health and ultimately affect function in older adults. Thus, the purpose of this study is to develop minimally invasive measures that will allow us to accurately assess and detect changes in fuel metabolism and circadian rhythms in older adults following time-restricted eating.

Description:

A growing body of evidence indicates the mitochondria have an important role in the etiologies of many chronic diseases as well as the onset of physical disability in older adults. Although it is recognized that the mitochondria have an important role in many functions relevant to healthy aging, the direct assessment of mitochondrial function in humans is complicated and typically involves a muscle biopsy. Muscle tissue obtained from a biopsy can be used to provide an index of mitochondrial function, but only at a single time point. Some individuals may be discouraged from participating in research studies involving biopsies due to the perceived pain and risk involved. Why there is a decrease in mitochondrial function with aging remains under debate, but emerging science indicates that there is a clear connection between mitochondrial biogenesis and function with fuel metabolism and circadian rhythms. Thus, the purpose of this development project is to develop relatively non-invasive measures that are sensitive to fuel metabolism and circadian health which can serve studies conducted within the University of Florida's Pepper Center in the coming years. In the proposed project, we will investigate the extent to which our measures of fuel utilization and circadian health markers are time stable and also sensitive to change following an intervention of time restricted eating, which is expected to impact these variables. To our knowledge, no study has assessed fuel utilization patterns or circadian health markers in overweight older adults. Measurements of altered mitochondrial oxidation with a preference toward fat metabolism obtained from a blood sample would provide a sensitive biomarker that is relatively easy to obtain from participants for future interventions studies. The use of continuous glucose monitoring may also be used as surrogate measure of adherence to lifestyle interventions involving calorie restriction and/or intervention fasting, in future studies. In addition to fuel utilization, there is growing recognition that age-related disease conditions and functional decline are associated with disruption of circadian rhythms. These observations raise the possibility that targeting circadian rhythms through timing lifestyle cues, such as meal timing, could be health promoting and may also reduce age associated declines in mobility. The ability to assess markers of circadian and metabolic health in minimally invasive ways through temperature and glucose monitoring, will provide potential valuable measures for explanatory or outcome measures in future studies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: March 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years and older

Eligibility

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 (<150 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)
• HbA1c < 5.7 %

Exclusion Criteria:

• Fasting >12 hours per day
• Actively trying to lose weight by participating in formal weight loss program or significantly restricting calorie intake
• Resting heart rate of >120 beats per minute, systolic blood pressure > 180 mmHg and/or diastolic blood pressure of > 100 mmHg
• Unstable angina, heart attack or stroke in the past 3 months
• Continuous use of supplemental oxygen to manage a chronic pulmonary condition or heart failure
• Rheumatoid arthritis, Parkinson's disease or currently on dialysis
• Active treatment for cancer in the past year
• Diabetes Mellitus
• Known history of skin sensitivity or allergic reaction to adhesives
• 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

Related Conditions & MeSH terms

• Aging

Intervention

Other:
• Time Restricted Eating Intervention
All participants will be asked to adhere to suggested fasting and feeding periods throughout the 8 week study period. These participants will self-monitor eating and sleeping habits as well to present to study staff at checkpoints. Self-reported information will be used during group-mediated intervention sessions throughout the duration of the study, as well.

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Florida	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

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* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Cellular Fuel Utilization	Fuel preference for mitochondrial energy production of isolated white blood cells (WBC) will be assessed using Agilent/Seahorse technology (XFe96 Flux Analyzer) for high-throughput measurement of mitochondrial oxygen bioenergetic function. We will use the Mito Fuel Flex Test assay (Agilent/Seahorse) to measure basal state mitochondrial fuel oxidation in live cells by using a set of substrates and inhibitors. This assay allows assessing the cell's ability to switch oxidative pathways in meeting basal energetic demands, and the relative contributions of glucose, glutamine and long chain fatty acid oxidation to basal respiration. This is completed by a 12-hour fasting blood draw.	Assessing change between Baseline and Week 8
Primary	Change in daily blood glucose levels	A "flash glucose monitor/sensor" (CGM; FreeStyle Libre PRO) will be used to assess the changes in 24-hour blood glucose levels. The FreeStyle Libre sensor is easy to apply and wear and can provide every five-minute glucose data to research monitors for up to 14 days. We will replace the CGM approximately every 2 weeks. In this study, we will use the Freestyle PRO thus the participants will be blinded to the data. We will evaluate pattern changes in daily glycemic excursions by week of the study as well as weekly averages and standard deviation by 6-hour time block.	Assessing change between Baseline and Week 8
Primary	Change in circadian rhythm gene BMAL1	Whole blood will be collected in Tempus™ Blood RNA Tubes with RNA isolated using the Tempus™ Spin RNA Isolation Kit according to the manufacturer (Applied Biosystems). Relative gene expression of Bmal1 will be analyzed using quantitative real-time polymerase chain reaction (PCR).	Assessing change between Baseline and Week 8
Primary	Change in Heart rate will be assessed by the Oura ring.	The goal of this development measure is to create a composite measure of circadian health using Wearable Technology (i.e., the Oura ring) that continuously tracks heart rate (beats per minute). The Oura ring is a Bluetooth Smart device and is only active for short periods of time. Data is transmitted continuously when the ring syncs with the app. Additionally, the Bluetooth signal and advertising are turned off when an individual is inactive or sleeping. Participants will be provided with Oura ring and instructed to wear it for the entire course of the study.	Assessing change between Baseline and Week 8
Primary	Change in circadian rhythm gene CLOCK	Whole blood will be collected in Tempus™ Blood RNA Tubes with RNA isolated using the Tempus™ Spin RNA Isolation Kit according to the manufacturer (Applied Biosystems). Relative gene expression of CLOCK will be analyzed using quantitative real-time polymerase chain reaction (PCR).	Assessing change between Baseline and Week 8
Primary	Change in body temperature will be assessed by the Oura ring.	The goal of this development measure is to create a composite measure of circadian health using Wearable Technology (i.e., the Oura ring) that tracks body temperature in Fahrenheit (°F). The Oura ring is a Bluetooth Smart device and is only active for short periods of time. Data is transmitted continuously when the ring syncs with the app. Additionally, the Bluetooth signal and advertising are turned off when an individual is inactive or sleeping. Participants will be provided with Oura ring and instructed to wear it for the entire course of the study.	Assessing change between Baseline and Week 8
Primary	Change in activity level will be assessed by the Oura ring.	This development measure aims to create a composite measure of circadian health using Wearable Technology (i.e., the Oura ring) that provides daily activity level scores. The Oura ring is a Bluetooth Smart device and is only active for short periods. Data is transmitted continuously when the ring syncs with the app. Additionally, the Bluetooth signal and advertising are turned off when an individual is inactive or sleeping. Participants will be given an Oura ring and instructed to wear it for the entire course of the study.	Assessing change between Baseline and Week 8
Primary	Change in circadian rhythm gene Nfil2	Whole blood will be collected in Tempus™ Blood RNA Tubes with RNA isolated using the Tempus™ Spin RNA Isolation Kit according to the manufacturer (Applied Biosystems). Relative gene expression of Nfil2 will be analyzed using quantitative real-time polymerase chain reaction (PCR).	Assessing change between Baseline and Week 8
Primary	Change in circadian rhythm gene Nr1d1	Whole blood will be collected in Tempus™ Blood RNA Tubes with RNA isolated using the Tempus™ Spin RNA Isolation Kit according to the manufacturer (Applied Biosystems). Relative gene expression of Nr1d1 will be analyzed using quantitative real-time polymerase chain reaction (PCR).	Assessing change between Baseline and Week 8
Primary	Change in circadian rhythm gene Dbp	Whole blood will be collected in Tempus™ Blood RNA Tubes with RNA isolated using the Tempus™ Spin RNA Isolation Kit according to the manufacturer (Applied Biosystems). Relative gene expression of Dbp will be analyzed using quantitative real-time polymerase chain reaction (PCR).	Assessing change between Baseline and Week 8
Primary	Change in circadian rhythm gene Cry1	Whole blood will be collected in Tempus™ Blood RNA Tubes with RNA isolated using the Tempus™ Spin RNA Isolation Kit according to the manufacturer (Applied Biosystems). Relative gene expression of Cry1 will be analyzed using quantitative real-time polymerase chain reaction (PCR).	Assessing change between Baseline and Week 8
Primary	Change in circadian rhythm gene Per2	Whole blood will be collected in Tempus™ Blood RNA Tubes with RNA isolated using the Tempus™ Spin RNA Isolation Kit according to the manufacturer (Applied Biosystems). Relative gene expression of Per2 will be analyzed using quantitative real-time polymerase chain reaction (PCR).	Assessing change between Baseline and Week 8
Primary	Change in heart rate variability will be assessed by the Oura ring.	The goal of this development measure is to create a composite measure of circadian health using Wearable Technology (i.e., the Oura ring) that tracks heart rate variability (HRV) in milliseconds (ms). The Oura ring is a Bluetooth Smart device and is only active for short periods. Data is transmitted continuously when the ring syncs with the app. Additionally, the Bluetooth signal and advertising are turned off when an individual is inactive or sleeping. Participants will be provided with Oura ring and instructed to wear it for the entire course of the study.	Assessing change between Baseline and Week 8
Primary	Change in sleep patterns will be assessed by the Oura ring.	This development measure aims to create a composite measure of circadian health using Wearable Technology (i.e., the Oura ring) that provides sleep patterns scores. The Oura ring is a Bluetooth Smart device and is only active for short periods. Data is transmitted continuously when the ring syncs with the app. Additionally, the Bluetooth signal and advertising are turned off when an individual is inactive or sleeping. Participants will be provided with an Oura ring and instructed to wear it for the entire course of the study.	Assessing change between Baseline and Week 8
Secondary	Change in anthropometric measurements	Height is measured in centimeters (cm) using a stadiometer. Bodyweight will be measured in kilograms (kg) following the removal of excess clothing and shoes with calibrated scales. Weight and height will be combined to report BMI in kg/m^2. Waist circumference is taken at the mid-point (cm) between the participant's lowest rib and the top of the participants' hip bone.	Assessing change between Baseline and Week 8
Secondary	Change in Body Composition	Body composition analysis will be performed in lower and upper body compartments using Hologic software. Values of fat-free mass (FFM) will be calculated after removing mass due to bone mineral content (BMC) using the equation, (FFM+BMC)-BMC=FFM.	Assessing change between Baseline and Week 8
Secondary	Change in walking speed.	Walking Speed will be assessed by the 6 Minute Walk test. The 6 Minute Walk test is a valid and reliable measure of physical function in numerous studies. Individuals will be asked to walk as quickly and safely as possible at a pace that can be maintained for six minutes. The distance completed in 6 minutes will be recorded. The 6 Minute Walk test will be administered by a trained examiner.	Assessing change between Baseline and Week 8
Secondary	Change in grip strength	Isometric handgrip strength is a commonly used measure of upper body skeletal muscle function and is widely used as a general indicator of functional status.	Assessing change between Baseline and Week 8
Secondary	Change in Whole Body Fuel Utilization	Participants will be fitted with a mask and harness and oxygen consumption and carbon dioxide production will be measured using a portable Cosmed K5. Participants will be asked to refrain from volitional exercise for the prior 24 hrs and come into the lab after an overnight fast. The mask will be placed over the mouth and nose in a thermoneutral environment. Resting metabolic rate (RMR) will be collected for 45 min and the final 30 min of data will be averaged. Movement or sleeping during the test will be noted, and these time periods will be excluded from RMR calculation using the Weir formula. RMR values will be adjusted for lean mass. Respiratory quotient (RQ) will be calculated as carbon dioxide (CO2) produced divided by oxygen (O2) consumed, protein oxidation during stable evaluation (within a coefficient of variation (CV) <5%). A high RQ closer to 1.0 indicates more carbohydrate production whereas the RQ for fat is 0.7 and for ketones is 0.66 (hypocaloric) to 0.73 (eucaloric).	Assessing change between Baseline and Week 8
Secondary	Change in Cognitive Function - Memory	A valid cognitive battery (NIH Toolbox) will be used in this study to assess an aspect of cognitive performance including memory.	Assessing change between Baseline and Week 8
Secondary	Change in Physical Function	Physical Function be assessed by the Short Physical Performance Battery to assess functional performance on different tasks including timed short distance walk, repeated chair stands, and a balance test. The Short Physical Performance Battery will be administered by a trained examiner	Assessing change between Baseline and Week 8
Secondary	Change in Cognitive Function - Processing speed	A valid cognitive battery (NIH Toolbox) will be used in this study to assess an aspect of cognitive performance including processing speed.	Assessing change between Baseline and Week 8
Secondary	Chang in Cognitive Function - Attention	A valid cognitive battery (NIH Toolbox) will be used in this study to assess an aspect of cognitive performance including attention.	Assessing change between Baseline and Week 8
Secondary	Change in Cognitive Function - Inhibitory Control	A valid cognitive battery (NIH Toolbox) will be used in this study to assess an aspect of cognitive performance including inhibitory control.	Assessing change between Baseline and Week 8