Impact of Time-Restricted Eating on Metabolic and Neuroendocrine Homeostasis, Inflammation and Oxidative Stress in Metabolic Syndrome

Study Overview
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Brief Summary
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The main purpose of the clinical trial is to determine the health impact of a dietary intervention known as time-restricted eating (TRE) in patients with metabolic syndrome (defined as the presence of elevated fasting plasma glucose and two or more of the following criteria: increased waist circumference, elevated fasting plasma triglycerides, reduced high-density lipoprotein-cholesterol, elevated blood pressure) and self-reported dietary intake of ≥14 hours per day. Participants will reduce the amount of time they eat to 10 hours per day over a 12-week monitored intervention followed by a 12-week self-directed intervention and will log their dietary intake using a smartphone application (myCircadianClock (mCC) app). Glucose homeostasis (blood glucose levels will be monitored continuously for 2 weeks at the baseline, at the end of the monitored intervention, and at the end of the self-directed intervention using a continuous glucose monitor), and other metabolic, neuroendocrine, inflammatory and oxidative stress/antioxidant defense biomarkers, body weight and composition, blood pressure, heart rate, sleep and activity (using mCC app), personal sense of wellness and dietary timing (using health questionnaires) will be evaluated at the baseline, at the end of the monitored intervention, and at the end of the self-directed intervention.

Detailed Description
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Metabolic syndrome occurs in approximately 30% of adults and is associated with increased risk of cardiovascular disease and type 2 diabetes. Circadian rhythm disruption due to lifestyle including erratic eating patterns may lead to metabolic and neuroendocrine dysfunction, inflammation, oxidative stress, and cardiometabolic diseases. Maintaining a daily rhythm of eating and fasting cycles sustains a robust circadian rhythm which improves cellular bioenergetics and metabolism. Recent studies support the notion that restricting a period of food intake to 8-12 hours a day (time-restricted eating, TRE) can prevent and reverse obesity and metabolic dysfunction. The main purpose of the clinical trial is to determine the health impact of TRE in patients with metabolic syndrome (defined as the presence of elevated fasting plasma glucose and two or more of the following criteria: increased waist circumference, elevated fasting plasma triglycerides, reduced high-density lipoprotein-cholesterol, elevated blood pressure) and self-reported dietary intake of ≥14 hours per day. Participants will reduce the amount of time they eat to 10 hours per day over a 12-week monitored intervention followed by a 12-week self-directed intervention and will log their dietary intake using a smartphone application (myCircadianClock (mCC) app, developed by the Salk Institute for Biological Studies). The participants will select a 10-h eating window that best suits their lifestyle. All food/beverages except water must be consumed within the time-interval. No further dietary restrictions will be applied. The participants will be provided with behavioral nutritional counseling by a dietician. Glucose homeostasis (blood glucose levels will be monitored continuously for 2 weeks at the baseline, at the end of the monitored intervention, and at the end of the self-directed intervention using a continuous glucose monitor), and other metabolic, neuroendocrine, inflammatory and oxidative stress/antioxidant defense biomarkers, body weight and composition, blood pressure, heart rate, sleep and activity (using mCC app), personal sense of wellness and dietary timing (using health questionnaires) will be evaluated at the baseline, at the end of the monitored intervention, and at the end of the self-directed intervention. The investigators will assess for compliance with TRE using mCC app.

Official Title
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Impact of Time-Restricted Eating on Metabolic and Neuroendocrine Homeostasis, Inflammation and Oxidative Stress in Patients With Metabolic Syndrome: the TREMNIOS Pilot Clinical Trial

Conditions
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Metabolic Syndrome, Overweight or Obesity, PreDiabetes, Weight Loss, Quality of Life

Intervention / Treatment
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* Behavioral: Time-Restricted Eating


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metabolic syndrome, defined as the presence of elevated fasting plasma glucose ≥ 100 mg/dL and two or more of the following criteria: Elevated waist circumference: ≥ 102 cm in men, ≥ 88 cm in women; Fasting plasma triglycerides ≥ 150 mg/dL (or on drug treatment for elevated triglycerides); Reduced High-density lipoprotein (HDL)-cholesterol < 40 mg/dL in men, < 50 mg/dL in women (or drug treatment for reduced HDL-cholesterol); Elevated blood pressure, Systolic blood pressure ≥ 130 mm Hg and/or diastolic blood pressure ≥ 85 mm Hg (or drug treatment for hypertension). BMI > 25 Duration of eating period ≥ 14 hours/day. Own a Smartphone with Apple Operating System (OS) or Android OS. Exclusion Criteria: Diagnosis of diabetes. Pregnant or lactating women. Active smoking or illicit drug use or history of treatment for alcohol abuse. Shift work. Caregivers for dependent requiring nocturnal care. Planned travel over time zones during the study period. History of major adverse cardiovascular event within the past 1 year (acute coronary syndrome, percutaneous coronary intervention, coronary artery bypass graft surgery, hospitalization for congestive heart failure, stroke/transient ischemic attack) or current uncontrolled arrhythmia. Uncontrolled medical conditions due to rheumatologic, hematologic, oncologic, infectious, gastrointestinal, psychiatric, nephrological, or endocrine diseases. Known history of an eating disorder. Currently enrolled in a weight-loss or weight-management program. Special or prescribed diet for other reasons (e.g. Celiac disease). Current treatment with antidepressants, medications affecting appetite, or immunosuppression. History of bariatric surgery. A score of > 16 on the Epworth Sleepiness Scale. Depression determined by the Beck Depression Inventory. Failure to use the smartphone app for documentation during a 2-week baseline period.

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Time-Restricted Eating<br> | Behavioral: Time-Restricted Eating<br>* Participants will reduce the amount of time they eat to 10 hours per day over a 12-week monitored intervention followed by a 12-week self-directed intervention and will log their dietary intake using a smartphone application (mCC app). The participants will select a 10-h eating window that best suits their lifestyle. All food/beverages except water must be consumed within the time-interval. No further dietary restrictions will be applied. The participants will be provided with behavioral nutritional counseling by a dietician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight | Body weight (kg) as measured in fasted state on a digital scale | Baseline and after 14 weeks | 
| Change in fasting glucose concentration | Fasting plasma glucose concentration (mg/dl) | Baseline and after 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight | Body weight (kg) as measured in fasted state on a digital scale | Changes from baseline. Fasted state at baseline, after 14 weeks, and after 26 weeks | 
| Body mass index | Body mass index (kg/m^2) as calculated from body weight (kg) and height (m) | Changes from baseline. Fasted state at baseline, after 14 weeks, and after 26 weeks | 
| Mean glucose | Glucose levels as measured by continuous glucose monitor (mg/dl) for 14 days at baseline, after 14 weeks, and after 26 weeks | Changes from baseline. Measured at baseline, after 14 weeks, and after 26 weeks | 
| Fasting glucose | Fasting glucose levels as measured by continuous glucose monitor (mg/dl) for 14 days at baseline, after 14 weeks, and after 26 weeks | Changes from baseline. Measured at baseline, after 14 weeks, and after 26 weeks | 
| Lipids | Fasting blood concentrations of lipids: total cholesterol (mg/dl), LDL cholesterol (mg/dl), HDL cholesterol (mg/dl), and triglycerides (mg/dl) | Changes from baseline. Measured in the blood in the fasted state at baseline, after 14 weeks, and after 26 weeks | 
| Fat mass | Fat mass percentage (%) as measured by body composition analyzer (using bioelectric impendence technology) | Changes from baseline. Fasted state at baseline, after 14 weeks, and after 26 weeks | 
| HbA1c | HbA1c (%) assessed from blood samples | Changes from baseline. Fasted state at baseline, after 14 weeks, and after 26 weeks | 
| Metabolic and neuroendocrine biomarkers | Fasting blood concentrations of metabolic and neuroendocrine biomarkers including but not limited to: free fatty acids, insulin, insulin-like growth factor-1, resistin, adiponectin, leptin, visfatin, irisin, ghrelin, omentin-1, and melatonin | Changes from baseline. Fasted state at baseline, after 14 weeks, and after 26 weeks | 
| Inflammatory biomarkers | Fasting blood concentrations of inflammatory biomarkers including but not limited to: high sensitivity C-reactive protein, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-α, tumor growth factor-β1, growth/differentiation factor 15 | Changes from baseline. Fasted state at baseline, after 14 weeks, and after 26 weeks | 
| Oxidative stress/antioxidant defense biomarkers | Fasting blood concentrations of oxidative stress/antioxidant defense biomarkers including but not limited to: superoxide dismutase-1, catalase, glutathione peroxidase, oxidized LDL, thiobarbituric acid reactive substances, conjugated dienes, malondialdehyde, 4-hydroxynonenal, vitamin A, and vitamin E | Changes from baseline. Fasted state at baseline, after 14 weeks, and after 26 weeks | 
| Waist circumference | Waist circumference (cm) as measured using tape measure | Changes from baseline. Fasted state at baseline, after 14 weeks, and after 26 weeks | 
| Blood pressure | Systolic and diastolic blood pressure (mmHg) measured under resting and fasting conditions | Changes from baseline. Fasted state at baseline, after 14 weeks, and after 26 weeks | 
| Heart rate | Heart rate (bpm) measured under resting conditions during measurements of blood pressure | Changes from baseline. Measured at baseline, after 14 weeks, and after 26 weeks | 
| Energy intake | Energy intake (kcal/day) assessed from diet records | Registered at baseline, after 14 weeks, and after 26 weeks | 
| Timing of dietary intake | Timing of dietary intake (hh:mm) assessed from diet records and from the chrono-nutrition questionnaire | Changes from baseline. Registered at baseline, after 14 weeks, and after 26 weeks | 
| Self-reported sleepiness | Self-reported sleepiness as assessed from the questionnaire the Epworth Sleepiness Scale | Changes from baseline. Assessed at baseline, after 14 weeks, and after 26 weeks | 
| Self-reported sleep quality | Self-reported sleep quality as assessed from the questionnaire Pittsburgh Sleep Quality Index | Changes from baseline. Assessed at baseline, after 14 weeks, and after 26 weeks | 
| Self-reported chronotype | Self-reported chronotype as assessed from the Munich Chronotype Questionnaire | Changes from baseline. Assessed at baseline, after 14 weeks, and after 26 weeks | 
| Self-reported overall health and wellbeing | Self-reported overall health and wellbeing as assessed from the questionnaire Self-reported health (SF-36 health survey) | Changes from baseline. Assessed at baseline, after 14 weeks, and after 26 weeks | 
| Duration of eating period | Duration from the first to last caloric intake over 24-hour cycle, collected via the smartphone app (mCC app) | Changes from baseline. Assessed at baseline, after 14 weeks, and after 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fasting, Time-Restricted Eating, Circadian Rhythm, Glucose Homeostasis, Metabolic Syndrome, Overweight, Obesity, PreDiabetes, Weight Loss, Metabolic Homeostasis, Neuroendocrine Biomarkers, Inflammation, Oxidative Stress