TREAT to Improve Cardiometabolic Health

Study Overview
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Brief Summary
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Over half of American adults have overweight or obesity and are at high risk of developing type 2 diabetes and cardiovascular diseases. Although caloric restriction has many health benefits, it is difficult to sustain overtime for most people. Time restricted eating (TRE), a novel type of intermittent fasting, facilitates adherence to the intervention and results in weight loss and improvement of metabolism. The investigators propose to to examine the efficacy of self monitoring and TRE (10-h/d) vs. self-monitoring and habitual prolonged eating duration ( HABIT) (13 hours/d) on weight loss and body composition, metabolic function and circadian biology, in metabolically unhealthy adults aged 50 to 75 y old, with overweight or obesity. The investigators hypothesize that TRE, compared to habitual long duration of eating, will decrease cardiovascular risk burden.

Detailed Description
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American adults have a high prevalence of overweight, obesity and prediabetes. Small weight loss delays the progression to type 2 diabetes and decrease cardiovascular risk, yet adherence to long term calorie restriction is difficult to sustain. There is an urgency to find effective, easy-to implement and sustain, and affordable life style interventions. Restricting the food intake interval, or time restricted eating (TRE) has been shown in small-scale pilot studies to result in weight loss and improve metabolism, while being less challenging than calorie count. We propose to rigorously assess the efficacy and sustainability of self-monitoring with and without TRE, administered via a smartphone application, on weight loss and decreased cardiovascular risk. To achieve this goal, metabolically unhealthy mid-life adults with overweight or obesity who habitually eat for more than 13h/day, will be randomized to a self monitoring and restricted eating window to 10h/d (TRE) or to a self-monitoring and habitual eating window (13h, HABIT), and followed up to 12 months. Ambulatory measures of food intake, sleep, physical activity and glucose, and outpatient well controlled studies will be done to determine the effect of TRE versus habitual eating duration (HABIT), as well as the mediators of these effects. Hypotheses: 1) TRE vs. HABIT will result in decreased fat mass, measured by quantitative magnetic resonance, and effect mediated via decreased daily total energy intake, measured by double labeled water; 2) TRE vs. HABIT will result in lower insulin resistance, lower glycemia and shift in fuel utilization preferentially to lipid mobilization; 3) Adherence to the TRE intervention will be associated with greater weight loss at 3 months and weight maintenance at 12 months. Results from this study will provide important insights into understanding the physiological and molecular interactions between restricting daily eating interval and metabolic function, and could provide evidence for using TRE interventions to improve metabolic health and decrease cardiovascular risk in the large number of mid-life and older Americans in great need of life style intervention.

Official Title
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New York TREAT (Time Restricted EATing) to Improve Cardiometabolic Health Study

Conditions
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Overweight and Obesity, Prediabetes

Intervention / Treatment
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* Behavioral: TRE
* Behavioral: HABIT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age: 50-75y old BMI ≥25 and ≤45 kg/m2 a diagnosis of prediabetes AND/OR fasting glucose 100 mg/dL and/or HbA1c 5.7% OR Type 2 Diabetes diet-controlled and/or treated with metformin AND meeting 2 or more of the following metabolic syndrome criteria: diagnosis of hypertension on stable medication regimen blood pressure >120/>80 mmHg A diagnosis of dyslipidemia on stable regimen triglycerides 150 mg/dL HDL cholesterol men <40 mg/dL and women <50 mg/dL waist circumference men: >102 cm (>40 in); women >88 cm (>35 in) in possession of a smart phone (iPhone or Android) 70% of days with logging adherence (2 or more log entries/day separated by at least 5h) Sleep duration 6-h, with habitual self-reported wake up time >5AM and before 11 AM and average self reported bed time <2AM habitually eat breakfast with weight stability within 5% of screening for the last 3 months English speaking (the App has not yet been translated) must live in the New York City metro area Exclusion criteria: sleep disorder, e.g. known obstructive sleep apnea (OSA) on CPAP, severe OSA with apnea-hypopnea index >30 events/h, significant daytime symptoms of OSA, periodic limb movements of sleep, narcolepsy, current shift work or in last 6-mo, travel more than 1 time zone during intervention; severe insomnia with score 15 on Insomnia Severity Index significant organ system dysfunction/disease: severe pulmonary, kidney or cardiovascular disease; evidence of active illness (e.g., fever) history of seizure disorder previous bariatric surgery or on weight loss medication history of or current significant food intake or psychiatric disorder use of dietary supplements and/or medications known to affect sleep, circadian rhythms or metabolic function smoking tobacco or using illegal or recreational drugs consume excessive alcohol (women: >14 drinks/wk; men: >21 drinks/wk) anemia (hemoglobin <10 g/dl and hematocrit <30%) have conditions that render individual unable to complete all testing procedures [e.g., unable to stay overnight or frequent travel across 1 time zones] extreme early and late chronotypes (> 2AM bed time and wake up time before 5AM and > 11AM) severe food allergies unwilling/unable to provide informed consent

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Metabolically unhealthy mid-life adults with overweight or obesity who habitually eat for more than 13h/day, will be randomized to a restricted eating window to 10h/d (TRE group) or to their habitual eating window (≥ 13h, HABIT group), and followed up to 12 months.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HABIT Group<br>Participants randomized to the HABIT group will maintain their habitual eating schedule (≥13-h). | Behavioral: HABIT<br>* The HABIT intervention will be administered and monitored via the study app. It combines self-monitoring behavior, positive reinforcement based on number of log entries, and basic lifestyle text messages. It also allows research staff to monitor in real-time, via the backend cloud, adherence to self-monitoring.<br>|
| Experimental: TRE Group<br>Participants randomized to TRE will reduce their eating window to a self-selected eating window (≤10-h). | Behavioral: TRE<br>* The TRE intervention will be administered and monitored via the study app. It combines self-monitoring behavior, daily eating window reminders, positive reinforcement based on number of log entries or based on meeting eating widow target, and basic lifestyle text messages. It also allows research staff to monitor in real-time, via the backend cloud, adherence to self-monitoring, and to reducing the eating window.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fat mass | Changes in fat mass (kg) will be measured by quantitative magnetic resonance (QMR) on day 0 and day 13 of ambulatory assessments at the 0 and 3 month study period, and again at 12 months. | 0, 3, and 12 months | 
| Energy intake | Energy intake (EI) will be calculated from total daily energy expenditure (EE) measured by doubly labeled water (DLW), and changes in body energy stores (ΔES), measured by QMR over the 2-wk ambulatory assessments of the 0 and 3 month study periods: EI (kcal/d) = EEDLW + ΔES. | 0, 3 months | 
| Body weight | Changes in body weight (kg) will be measured to the nearest 0.01 kg with a digital scale at 0 and 3 months, and again at 12 months. | 0, 3, 12 months | 
| Insulin resistance (HOMA-IR) | Fasting serum insulin and plasma glucose concentrations will be used to calculate changes in insulin resistance (HOMA-IR): [fasting insulin (mU/mL) x fasting glucose (mmol/L)]/22.5 at 0 and 3 months, and again at 12 months. | 0, 3, 12 months | 
| Glucose levels | Glucose changes will be assessed by the total and incremental 24-hour glucose AUC, from ambulatory CGM at 0 and 3 months. | 0, 3,12 months | 
| Glucose variability | CGM data will be used to calculate standard measures of glucose variability (GV), including mean amplitude of glycemic excursion (MAGE) changes at 0 and 3 months. | 0, 3,12 months | 
| Sleep assessment | Sleep duration will be assessed by changes in bedtime, waketime, and total sleep time, recorded by actigraphy during the 2-wk ambulatory assessments at 0, 3, and 12 months. | 0, 3,12 months | 
| Adherence | Adherence will be assessed by % of days with at least 2 or more entries logged at least 5h apart/day | 0, 3,12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diet composition by ASA24 | % of carbs, fat and protein in diet by ASA24 on 3 non-consecutive days (2 weekdays and one weekend day) during each ambulatory assessment and during the 3 months intervention. | 0, 3, 12 months | 
| Matsuda Index (Insulin resistance) | Fasting and OGTT glucose and insulin levels are used to calculate the Matsuda index: 10,000/([fasting insulin (mU/mL)x fasting glucose (mmol/L)]x [mean OGTT insulin (mU/mL) x mean OGTT glucose (mmol/L)]) | 0, 3 months | 
| Insulinogenic Index | Calculated by the AUC insulin/AUC glucose during OGTT. | 0, 3 months | 
| Free fatty acids (FFA) | Measured from a fasting blood sample | 0, 3, 12 months | 
| Ketones | The concentration of ketones (beta-OH-butyrate) will be measured from a fasting blood sample. | 0, 3, 12 months | 
| Physical activity | Assessed by step count during 14 day ambulatory assessment periods at 0,3, and 12 months. | 0, 3, 12 months | 
| Inflammation markers | Measured from a fasting blood sample. | 0, 3, 12 months | 
| Oxidative stress | Measured from a fasting blood sample | 0, 3, 12 months | 
| Lipid profile | Measured from a fasting blood sample | 0, 3, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Overweight, Obesity, Metabolic syndrome, Time restricted eating, Diabetes, Prediabetes, Lifestyle intervention, Smartphone app