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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Quality of Life; Metabolic Syndrome; Weight Loss; PreDiabetes; Overweight or Obesity
• Intervention / Treatment: Behavioral: Time-Restricted Eating

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Bydgoszcz, Poland
    • Nicolaus Copernicus University, Collegium Medicum Bydgoszcz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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).

2. BMI > 25
3. Duration of eating period ≥ 14 hours/day.
4. Own a Smartphone with Apple Operating System (OS) or Android OS.

Exclusion Criteria:

1. Diagnosis of diabetes.
2. Pregnant or lactating women.
3. Active smoking or illicit drug use or history of treatment for alcohol abuse.
4. Shift work.
5. Caregivers for dependent requiring nocturnal care.
6. Planned travel over time zones during the study period.
7. 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.
8. Uncontrolled medical conditions due to rheumatologic, hematologic, oncologic, infectious, gastrointestinal, psychiatric, nephrological, or endocrine diseases.
9. Known history of an eating disorder.
10. Currently enrolled in a weight-loss or weight-management program.
11. Special or prescribed diet for other reasons (e.g. Celiac disease).
12. Current treatment with antidepressants, medications affecting appetite, or immunosuppression.
13. History of bariatric surgery.
14. A score of > 16 on the Epworth Sleepiness Scale.
15. Depression determined by the Beck Depression Inventory.
16. Failure to use the smartphone app for documentation during a 2-week baseline period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Time-Restricted Eating

Behavioral: Time-Restricted Eating; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nicolaus Copernicus University
• Collaborators: University of California, San Diego; Salk Institute for Biological Studies; Center for Obesity and Metabolic Disorders Treatment Bydgoszcz
• Investigators: Principal Investigator: Iwona Swiatkiewicz, MD, PhD, Nicolaus Copernicus University, Collegium Medicum Bydgoszcz

Publications and helpful links

General Publications

• Panda S. Circadian physiology of metabolism. Science. 2016 Nov 25;354(6315):1008-1015. doi: 10.1126/science.aah4967.
• Chaix A, Zarrinpar A, Miu P, Panda S. Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab. 2014 Dec 2;20(6):991-1005. doi: 10.1016/j.cmet.2014.11.001.
• Gill S, Le HD, Melkani GC, Panda S. Time-restricted feeding attenuates age-related cardiac decline in Drosophila. Science. 2015 Mar 13;347(6227):1265-9. doi: 10.1126/science.1256682.
• Pot GK, Almoosawi S, Stephen AM. Meal irregularity and cardiometabolic consequences: results from observational and intervention studies. Proc Nutr Soc. 2016 Nov;75(4):475-486. doi: 10.1017/S0029665116000239. Epub 2016 Jun 22.
• Gill S, Panda S. A Smartphone App Reveals Erratic Diurnal Eating Patterns in Humans that Can Be Modulated for Health Benefits. Cell Metab. 2015 Nov 3;22(5):789-98. doi: 10.1016/j.cmet.2015.09.005. Epub 2015 Sep 24.
• Sulli G, Manoogian ENC, Taub PR, Panda S. Training the Circadian Clock, Clocking the Drugs, and Drugging the Clock to Prevent, Manage, and Treat Chronic Diseases. Trends Pharmacol Sci. 2018 Sep;39(9):812-827. doi: 10.1016/j.tips.2018.07.003. Epub 2018 Jul 27.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2019
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: March 27, 2020
• First Submitted That Met QC Criteria: March 27, 2020
• First Posted (Actual): March 31, 2020

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 6, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Inflammation; Obesity; Overweight; Metabolic Syndrome; Oxidative Stress; Weight Loss; Circadian Rhythm; Fasting; Glucose Homeostasis; PreDiabetes; Time-Restricted Eating; Metabolic Homeostasis; Neuroendocrine Biomarkers
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Disease; Diabetes Mellitus; Overnutrition; Nutrition Disorders; Body Weight; Insulin Resistance; Hyperinsulinism; Body Weight Changes; Hyperglycemia; Syndrome; Inflammation; Metabolic Syndrome; Weight Loss; Prediabetic State; Glucose Intolerance; Overweight
• Other Study ID Numbers: NCU CM IRB 107/2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No