Assessment of Fuel Utilization and Circadian Rhythms in Overweight, Older Adults Following Time Restricted Eating - Phase 2 (FAR Phase 2)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Change in Heart rate will be assessed by the Oura ring.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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 %
排除标准
- •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
研究组 & 干预措施
Time Restricted Eating intervention
Participants will be asked to stop eating by 7 PM every day and to fast for a target of 16 hours per day for 8 weeks. During the first two weeks of the intervention, participants will gradually ramp up to a full 16-hour fasting period (Week 1 - fast for 12-14 hours per day, Week 2 - fast for 14-16 hours per day, Week 3 - 8 - fast for 16 hours per day). Participants will be allowed to consume calorie-free beverages, tea, black coffee, sugar-free gum, and they will be encouraged to drink plenty of water throughout the entire intervention period. Additionally, they will be asked to keep a Fasting and Sleeping diary logging their eating habits and sleep quality.
干预措施: Time Restricted Eating Intervention (Other)
结局指标
主要结局
Change in Heart rate will be assessed by the Oura ring.
时间窗: Assessing change between Baseline and Week 8
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.
Change in activity level will be assessed by the Oura ring.
时间窗: Assessing change between Baseline and Week 8
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.
Change in circadian rhythm gene Nfil2
时间窗: Assessing change between Baseline and Week 8
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).
Change in Cellular Fuel Utilization
时间窗: Assessing change between Baseline and Week 8
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.
Change in circadian rhythm gene CLOCK
时间窗: Assessing change between Baseline and Week 8
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).
Change in body temperature will be assessed by the Oura ring.
时间窗: Assessing change between Baseline and Week 8
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.
Change in circadian rhythm gene Per2
时间窗: Assessing change between Baseline and Week 8
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).
Change in daily blood glucose levels
时间窗: Assessing change between Baseline and Week 8
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.
Change in circadian rhythm gene BMAL1
时间窗: Assessing change between Baseline and Week 8
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).
Change in sleep patterns will be assessed by the Oura ring.
时间窗: Assessing change between Baseline and Week 8
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.
Change in circadian rhythm gene Cry1
时间窗: Assessing change between Baseline and Week 8
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).
Change in heart rate variability will be assessed by the Oura ring.
时间窗: Assessing change between Baseline and Week 8
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.
Change in circadian rhythm gene Nr1d1
时间窗: Assessing change between Baseline and Week 8
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).
Change in circadian rhythm gene Dbp
时间窗: Assessing change between Baseline and Week 8
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).
次要结局
- Change in Body Composition(Assessing change between Baseline and Week 8)
- Change in Whole Body Fuel Utilization(Assessing change between Baseline and Week 8)
- Change in walking speed.(Assessing change between Baseline and Week 8)
- Chang in Cognitive Function - Attention(Assessing change between Baseline and Week 8)
- Change in Cognitive Function - Memory(Assessing change between Baseline and Week 8)
- Change in anthropometric measurements(Assessing change between Baseline and Week 8)
- Change in grip strength(Assessing change between Baseline and Week 8)
- Change in Physical Function(Assessing change between Baseline and Week 8)
- Change in Cognitive Function - Processing speed(Assessing change between Baseline and Week 8)
- Change in Cognitive Function - Inhibitory Control(Assessing change between Baseline and Week 8)