Fasting ENHANCE Pilot Study

Study Overview
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Brief Summary
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Grounded in the principles of geroscience, the proposed Fasting ENHANCE study will test whether a time restricted eating (TRE) regimen can improve cognitive function and other aspects of successful aging in a safe and sustainable manner in at risk overweight older adults. Specifically, this study will evaluate whether TRE can improve cognitive and physical function, as well as self-reported sleep, mood, and quality of life, in overweight, older adults (age > 65 years) who are at high risk of cognitive decline due to self-reported cognitive difficulties. Eligible participants will be assigned to either a TRE intervention, in which they will be instructed to fast for a target of 16 hours per day, or a successful aging (SA) comparison group for a 24-week period.

Detailed Description
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During the past century, persons aged >70 years represented the fastest growing segment of the US population with the life expectancy of older Americans steadily increasing, until the onset of COVID-19 in 2020. Unfortunately, the increase in lifespan has not been accompanied by an increase in health-span, which is the time-period in which a person is healthy and functionally independent. Rather, the aging population has been accompanied by an increase in the number of individuals living with chronic metabolic and neurocognitive disease conditions, including obesity, metabolic syndrome, and Alzheimer's disease and Related Disorders (ADRD). Moreover, poor metabolic health appears to be a risk factor for accelerated brain aging; therefore improving metabolic health may represent a strategy to improve long-term brain health. Although age-related biological and metabolic changes clearly have a role in the development of chronic health conditions and risk for ADRD, a growing body of research indicates lifestyle factors contribute to modifiable patho-physiological states that precede the development of many age-related chronic health conditions. Specifically, over-nutrition, sedentary lifestyle, and poor sleep habits have been directly linked with metabolic diseases, as well as cognitive decline and development of ADRD in later life. Our work and that of others has demonstrated that the rate of functional decline among older adults is highly influenced by biological and metabolic changes during aging, which are largely affected by lifestyle factors, namely dietary intake, sleep, and physical activity levels. Specifically, the investigators have shown that intermittent fasting (IF) regimens, particularly time restricted eating (TRE), can have positive effects on biological, metabolic, and functional health markers in middle-aged and older adults, similar to that of calorie restriction. These observations raise the possibility that interventions targeting the fundamental biology of human aging have the potential to delay, if not prevent, the onset of aging-associated conditions, such as ADRD. The unprecedented growth of the aging population has created an urgent need for promising interventions that can preserve older adult's capacity to live independently and function well. The scientific premise of this proposal is that a time-restricted eating intervention can target the cellular and metabolic alterations that underlie age-related metabolic and neurocognitive disease conditions and thereby extend health-span in the growing population of older adults who reported subjective cognitive decline.

Official Title
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Fasting to Provide Energy Needed to Help Adults in Need of Cognitive Enhancement (FASTING ENHANCE)

Conditions
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Overweight and Obesity, Time Restricted Feeding, Alzheimer Disease

Intervention / Treatment
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* Behavioral: Time Restricted Eating intervention
* Behavioral: Successful Aging Comparison Group (LEARN)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 65 years; Body Mass Index (BMI > 25 kg/m2) Normal age-, gender-, and education-adjusted performance on TICS-M (Telephone Interview for Cognitive Status) Responds yes to questions 1 (memory worse), 2 (word finding difficulties) or 3 (planning/organization difficulties) on the Subjective Cognitive Decline Questionnaire Reports onset of cognitive difficulties in past five years Reports they believe they are worse than others their age OR they have talked to a clinician about it. Provides informed consent and willing to be randomized to either intervention group. Exclusion Criteria: Failure to provide informed consent; Recent History or clinical manifestation of cardiovascular disease, diabetes, cholelithiasis, liver or renal disease, cancer, or progressive, degenerative neurologic disease (e.g., Parkinson's Disease, multiple sclerosis, ALS) Abnormal laboratory markers (e.g., renal or liver abnormalities, elevated potassium levels, or hemoglobin and hematocrit below the lower limit of normal) as determined by study physician. Significant cognitive impairment, defined as a scores below the cutoff for dementia on TICS-M Severe rheumatologic or orthopedic diseases (e.g., awaiting joint replacement, active inflammatory disease); Terminal illness with life expectancy less than 12 months, as determined by a physician; Other significant co-morbid disease (e.g. renal failure on hemodialysis) or severe psychiatric disorder (e.g. bipolar, schizophrenia); Current use of anabolic medications (i.e., growth hormones or testosterone), antidepressant medications, antipsychotic agents, monoamine oxidase inhibitors, anticholinesterase inhibitors (i.e., Aricept), anticoagulant therapies (aspirin use is permitted), or antibiotics; Excessive alcohol use (>14 drinks per week); History of drug or alcohol abuse (i.e., more than 5 drinks/day for males or more than 4 drinks/day for females); Planning to permanently leave the area in the next year; History of pulmonary disease, pneumonitis or interstitial lung disease; Current smoker or less than 3 years quit; Creatinine clearance < 30 ml/minute by estimated Glomerular Filtration Rate (eGFR); Fasting >12 hours per day Actively trying to lose weight by participating in formal weight loss program or significantly restricting calorie intake or weight loss > 5 lbs in the past month Resting heart rate of >120 beats per minute, systolic blood pressure > 180 mmHg 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 Insulin dependent diabetes mellitus Taking medications that preclude fasting for 16 hours (e.g. must be taken with food at least 12 hours apart) Participating in another clinical trial or has received an investigational product within 30 days prior to screening/enrollment Any condition that in the opinion of the investigator would impair ability to participate in the trial.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be assigned to either a time restricted eating intervention, in which they will be instructed to fast for a target of 16 hours per day, or a successful aging (SA) comparison group for a 24-week period. This Study will examine the effects of TRE on changes in cognitive function, as assessed by the Repeatable Battery of the Assessment of Neuropsychological Status (RBANS), examine the effects of TRE on cognitive physical function, as assessed by the six-minute walk and short physical performance battery, and examine the effects of TRE on changes in mood, sleep patterns, metabolic function, and self-reported quality of life.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Time Restricted Eating intervention<br>In the time restricted eating condition, participants will be instructed to fast for a target of 16 hours per day for a 24 week period. | Behavioral: Time Restricted Eating intervention<br>* In the TRE intervention, participants will be asked to fast for a target of 16 hours per day for a period of 24 weeks. The first few weeks will involve of a 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 - 16 - fast for 16 hours per day). Participants will be allowed to consume calorie-free beverages, tea, black coffee, sugar-free gum, and they will be encouraged to drink plenty of water throughout the entire intervention period. Participants will be asked to record the time of first and final food/drink consumption each day. Both the TRE and Successful Aging comparison group will be group-mediated, with equal number of contact visits from study staff consisting of 10 group sessions over 24 weeks.<br>* Other names: TRE intervention;|
| Active Comparator: Successful Aging Comparison Group (LEARN)<br>In the LEARN group, participants will be educated on health related topics similar to that of the TRE intervention for 24 weeks. | Behavioral: Successful Aging Comparison Group (LEARN)<br>* In the Successful Aging Comparison Group (LEARN), participants will attend lectures on topic relevant to healthy aging at the same frequency as the group meetings in the TRE intervention. Both the TRE and Successful Aging comparison group will be group-mediated, with equal number of contact visits from study staff consisting of 10 group sessions over 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Repeatable Battery of the Assessment of Neuropsychological Status (RBANS) | The RBANS is a neuropsychological battery of tests that has 4 repeatable forms that can be used longitudinally to measure cognitive change. It takes 30 minutes to administer and includes measures of five cognitive domains including immediate memory, visuospatial/constructional, language, attention, and delayed memory. This test is reliable in yielding results that recognize cognitive impairment associated with neurodegenerative disease. The RBANS can be used in predicting cognitive impairment with particular emphasis on the language and immediate memory subtests. | Baseline up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montreal Cognitive Assessment (MoCA) | The Montreal Cognitive Assessment is a 30-point assessment of mild cognitive impairment, which assesses the domains of attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Different versions of the test are given at the three time points to avoid learning effects between repeated administrations of the test. | Baseline up to Week 24 | 
| 6 Minute Walk Test | The 6 Minute Walk test measures the amount of distance the participant can complete on a standard walking course in six minutes without running or overexerting themselves. It has been found to be a valid and reliable measure of physical function in numerous studies. | Baseline up to Week 24 | 
| Short Physical Performance Battery (SPPB) | The SPPB will also be used to assess functional performance on different tasks including timed short distance walk, repeated chair stands, and a balance test. | Baseline up to Week 24 | 
| Grip Strength | Isometric grip strength, a commonly used measure of upper body skeletal function, will be assessed with a hand held dynamometer | 1st Day of Screening | 
| Pittsburgh Sleep Quality Index | Sleep will be assessed by the Pittsburgh Sleep Quality Index, a self-report tool which consists of 19-item scale that provides seven component scores (ranges 0-3): (a) subjective sleep quality (very good to very bad), (b) sleep latency (≤15 to >60 minutes), (c) sleep duration (≥7 to <5 hours), (d) sleep efficiency (≥85% to <65% hours sleep/ hours in bed), (e) sleep disturbances (not during the past month to ≥3 times per week), (f) use of sleeping medications (none to ≥3 times a week), and (g) daytime dysfunction (not a problem to a very big problem) with a total global score ranging from 0 to 21. | Baseline up to Week 24 | 
| State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA) | The State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA) was designed to assess cognitive and somatic symptoms of anxiety as they pertain to one's mood in the moment (state) and in general (trait). This measure has been validated in a sample of older adults. | Baseline up to Week 24 | 
| Geriatric Depression Scale | Symptoms of depression will be assessed by the Geriatric Depression Scale, a self-report questionnaire to measure depression in older adults. | Baseline up to Week 24 | 
| Short Form (SF) -12 Health Survey | This 12-item short form questionnaire assesses both mental and physical components of health-related quality of life. The SF-12 Health Survey assesses 8 general domains: physical activity limitation due to health problems, social activity limitation due to physical/emotional problems, daily role activity limitations due to physical health problems, body pain, general mental health, daily role activity limitation due to emotional problems, energy and fatigue, and general health perceptions. | Baseline up to Week 24 | 
| Pittsburgh Fatiguability Scale | The 26-item Pittsburgh Fatiguability Scale will be administered to measure perceived mental and physical fatigability. Questions are divided into 4 main categories: moderate to high-intensity activity (≥3.0 metabolic equivalents (METS), social activity, sedentary activity (≤1.5 METS), and lifestyle or light-intensity activity (1.6-2.9 METS). Higher scores suggest higher levels of perceived fatigability. | Baseline up to Week 24 | 
| Metabolic and Systemic biomarkers | Biomarkers of glucose regulation (HbA1C), systemic inflammation (C-reactive protein), and neurodegenerative diseases, Tau will be assessed. Samples will be measured in duplicate and the average of the two measures will be used for data analyses. | Baseline up to Week 24 | 
| Anthropometric Measurements. | Body weight will be measured following the removal of excess clothing and shoes with calibrated scales. Waist circumference is taken at the mid-point between the participant's lowest rib and the top of his/her hip bone. | 1st Day of Screening up to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aging, Time Restricted Eating, Overweight, Obesity, Alzheimer's Disease and Related Disorders (ADRD)