Efficacy and Feasibility of Time-restricted Eating on Cardiometabolic Health in Adults With Overweight/Obesity (EXTREME)

Efficacy and Feasibility of Time-restricted Eating on Cardiometabolic Health in Adults With Overweight/Obesity: The EXTREME Study

In Spain, obesity epidemic is one of the leading contributors of chronic disease and disability. Obesity is associated with higher morbidity and all-cause mortality risk especially when fat is stored in the abdominal area (i.e., increased visceral adipose tissue, VAT). Although current approaches such as energy restriction may be effective at reducing body fat and improving cardiometabolic health, their long-term adherences are limited. Time-restricted eating (TRE; e.g., 8 hours eating: 16 hours fasting on a daily basis) is a recently emerged intermittent fasting approach with promising cardiovascular benefits. Results from pioneering pilot studies in humans are promising and suggest that simply reducing the eating time window from ≥12 to ≤8-10 hours/day improves cardiometabolic health. However, currently, there is no consensus regarding whether the TRE eating window should be aligned to the early or middle to late part of the day. The EXTREME study will investigate the efficacy and feasibility of three different 8 hours TRE schedules (i.e., early, late and self-selected) over 12 weeks on VAT (main outcome) and cardiometabolic risk factors (secondary outcomes) in adults with overweight/obesity and abdominal obesity. The final goal of the EXTREME study is to demonstrate the health benefits of a novel and pragmatic intervention for the treatment of obesity and related cardiometabolic risk factors; an approach readily adaptable to real-world practice settings, easy for clinicians to deliver, and intuitive for patients to implement and maintain in their lives.

Study Overview

• Status: Completed
• Conditions: Obesity, Abdominal; Time Restricted Feeding; Cardiometabolic Syndrome
• Intervention / Treatment: Behavioral: Early time-restricted eating; Behavioral: Late time-restricted eating; Behavioral: Self-selected time-restricted eating

• Study Type: Interventional
• Enrollment (Actual): 197
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Granada, Spain, 18011
    • University of Granada
  • Navarra
    • Pamplona, Navarra, Spain, 31006
      • Universidad Pública de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 30-60 years.
• Body mass index ≥25.0 and <40 kg/m2
• Weight stability (within 3% of screening weight) for >3 months prior to study entry.
• Sedentary lifestyle (<150 min/week of moderate-vigorous intensity exercise) for >3 months prior to study entry.
• Habitual eating window ≥12 hours.

• At least one of the following metabolic impairments:

  • High-density lipoprotein (HDL) cholesterol concentration <50 mg/dL for females and <40 mg/dL for males.
  • Low-density lipoprotein (LDL) cholesterol levels >100 mg/dL (or on medication to treat elevated LDL cholesterol levels).
  • Serum triglycerides concentration ≥150 mg/dL or on medication to treat elevated triglycerides.
  • Systolic blood pressure >130 mm Hg and/or diastolic blood pressure >85 mm Hg or already being treated with anti-hypertension medications.

  • Impaired glucose tolerance is defined as at least one of the following:

    • Fasting plasma glucose (PG) >100 mg/dL and <125 mg/dL.
    • Hemoglobin A1c between ≥5.7% and <6.5%.
    • Insulin resistance as measured by the Homeostatic Model Assessment of Insulin Resistance (HOMA2-IR) >1.8.

Exclusion Criteria:

• History of a major adverse cardiovascular event, clinically significant kidney, endocrine, or neurological disease, bariatric surgery, HIV/AIDS, known inflammatory and/or rheumatologic disease, cancer, or other medical condition in which fasting or exercise is contraindicated.
• Type 1 or Type 2 diabetes.
• Major psychiatric disorders, eating disorders, sleep disorders, or alcohol abuse.

Regular use of medication or compounds that may affect study outcomes (e.g., antidiabetic, steroids, beta-blockers, antibiotics, prebiotics, probiotics and symbiotics).

• Participating in a weight loss or a weight-management program.
• Pregnancy and lactation or planned pregnancy (within the study period).
• Caregiver for a dependent requiring frequent nocturnal care/sleep interruptions. Shift workers with variable hours (e.g., nocturnal). Frequent travel over time zones during the study period.
• Fear of needles and claustrophobia to magnetic resonance imaging (MRI).
• Being unable to understand and to accept the instructions or the study objectives and protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early time-restricted eating; Participants will eat ad libitum within an 8-hour early eating window. The first meal will be before 10 am (last meal before 18h). No calorie-containing food or beverage intake will be allowed outside the 8-hour eating window. Participants will also receive standard recommendations on healthy lifestyle based on Mediterranean dietary pattern and physical activity recommendations for weight loss and health promotion	Behavioral: Early time-restricted eating; Participants will eat ad libitum within an 8-hour early eating window starting not later than 10am. No calorie-containing food or beverage intake will be allowed outside the 8-hour eating window. Participants will also receive standard recommendations on healthy lifestyle based on Mediterranean dietary pattern and physical activity recommendations for weight loss and health promotion
Experimental: Late time-restricted eating; Participants will eat ad libitum within an 8-hour late eating window. The first meal will be at 13h or later (last meal not before 21h). No calorie-containing food or beverage intake will be allowed outside the 8-hour eating window. Participants will also receive standard recommendations on healthy lifestyle based on Mediterranean dietary pattern and physical activity recommendations for weight loss and health promotion	Behavioral: Late time-restricted eating; Participants will eat ad libitum within an 8-hour late eating window starting not earlier than 1pm. No calorie-containing food or beverage intake will be allowed outside the 8-hour eating window. Participants will also receive standard recommendations on healthy lifestyle based on Mediterranean dietary pattern and physical activity recommendations for weight loss and health promotion
Experimental: Self-selected time-restricted eating; Participants will self-selecte an 8-hour eating window to eat ad libitum. No calorie-containing food or beverage intake will be allowed outside the 8-hour eating window. Participants will also receive standard recommendations on healthy lifestyle based on Mediterranean dietary pattern and physical activity recommendations for weight loss and health promotion	Behavioral: Self-selected time-restricted eating; Participants will self-selected an 8-hour eating window to eat ad libitum. No calorie-containing food or beverage intake will be allowed outside the 8-hour eating window. Participants will also receive standard recommendations on healthy lifestyle based on Mediterranean dietary pattern and physical activity recommendations for weight loss and health promotion
No Intervention: Usual-care group; Participants will receive standard recommendations on healthy lifestyle based on Mediterranean dietary pattern and physical activity recommendations for weight loss and health promotion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in visceral adipose tissue	Visceral adipose tissue will be assessed by Magnetic Resonance Imaging (MRI)	Change from baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hepatic fat content	Hepatic fat content will be assessed by Magnetic Resonance Imaging (MRI)	Change from baseline to 12 weeks
Change in Pancreatic fat content	Pancreatic fat content will be assessed by Magnetic Resonance Imaging (MRI)	Change from baseline to 12 weeks
Change in Intramuscular fat content	Intramuscular fat content will be assessed by Magnetic Resonance Imaging (MRI)	Change from baseline to 12 weeks
Change in Hepatic elasticity	Hepatic elasticity will be assessed by US elastography	Change from baseline to 12 weeks
Change in Pancreatic elasticity	Pancreatic elasticity will be assessed by US elastography	Change from baseline to 12 weeks
Change in Fasting glucose metabolism	Fasting blood samples will be used to analyse different biomarkers of glucose metabolism	Change from baseline to 12 weeks
Change in Fasting lipid metabolism	Fasting blood samples will be used to analyse different biomarkers of lipid metabolism (e.g., triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol)	Change from baseline to 12 weeks
Change in Inflammatory profile	Fasting blood samples will be used to analyse inflammatory profile (e.g., C-reactive protein and interleukin 6)	Change from baseline to 12 weeks
Change in Hepatic profile	Fasting blood samples will be used to analyse hepatic profile (e.g., alkaline phosphatase, bilirubin, alanine transaminase and gamma-glutamyl transferase)	Change from baseline to 12 weeks
Change in Kidney profile	Fasting blood samples will be used to analyse kidney profile (e.g., creatinine and creatine kinase)	Change from baseline to 12 weeks
Change in Glycemia (Continuous Glucose Monitoring)	Glycemia will be assessed by Continuous Glucose Monitoring during 2 weeks	Change from baseline to 12 weeks
Change in Body weight	Body weight will be measured by a digital scale	Change from baseline to 12 weeks
Change in Body composition (Fat mass and fat free mass)	Body composition will be assessed by Dual-energy X-ray Absorptiometry (DXA)	Change from baseline to 12 weeks
Change in Anthropometric measures	Neck, hip and waist circumferences will be assessed by standard procedures	Change from baseline to 12 weeks
Change in Blood pressure	Systolic and Diastolic blood pressure will be assessed by standard procedures	Change from baseline to 12 weeks
Change in energy intake	Energy intake (kcal/day) will be assessed by 24h recalls	Change from baseline to 12 weeks
Change in macronutrients intake	Macronutrients intake (g/day and percentage of energy intake) will be assessed by 24h recalls	Change from baseline to 12 weeks
Change in dietary habits	Dietary habits will be assessed by food frequency questionnaires	Change from baseline to 12 weeks
Change in Food craving	Food craving will be assessed by the Food Craving Inventory (FCI)	Change from baseline to 12 weeks
Change in Appetitive traits	Appetitive traits will be assessed by the Adult Eating Behavior Questionnaire (AEBQ)	Change from baseline to 12 weeks
Change in Subjective sleep quality	Subjective sleep quality will be assessed by the Pittsburgh Sleep Quality Index (PSQI)	Change from baseline to 12 weeks
Change in Objectively sleep quality	Objectively sleep quality will be assessed by accelerometry	Change from baseline to 12 weeks
Change in Chronotype	Chronotype will be assessed by the Munich Chronotype Questionnaire (MCTQ)	Change from baseline to 12 weeks
Change in Morning-Evening type	Morning-Evening type will be assessed by the Morningness-Eveningness Questionnaire Self-Assessment Version.	Change from baseline to 12 weeks
Change Subjective physical activity levels	Subjective physical activity levels will be assessed by the International Physical Activity Questionnaire short form	Change from baseline to 12 weeks
Change Objectively physical activity levels	Objectively physical activity levels will be assessed by accelerometry	Change from baseline to 12 weeks
Change in Depression aspects	Depression aspects will be assessed by the Beck Depression Inventory Fast Screen (BDI-FS)	Change from baseline to 12 weeks
Change in Stress aspects	Stress aspects will be assessed by the Perceived Stress Scale (PSS)	Change from baseline to 12 weeks
Change in Anxiety aspects	Anxiety aspects will be assessed by the State-Trait Anxiety Inventory (STAI)	Change from baseline to 12 weeks
Change in General health	General health will be assessed by the EuroQol 5 dimensions 5 levels (EQ-5D-5L)	Change from baseline to 12 weeks
Change in Quality of life	Quality of life will be assessed by the Rand Short Form 36 (SF-36)	Change from baseline to 12 weeks
Change in Gut microbiota composition	DNA sequencing to determine gut microbiota composition (e.g., phylum and genera)	Change from baseline to 12 weeks
Change in Gut microbiota diversity	DNA sequencing to determine gut microbiota diversity (e.g., beta and alpha)	Change from baseline to 12 weeks
Feasibility of recruitment	Feasibility of recruitment (i.e., percent of response rate).	12 weeks
Feasibility of the intervention	Retention during the intervention (i.e., percent of attrition).	12 weeks
Adherence to the intervention	Adherence will be assessed by eating records	Every day during the intervention, up to 90 days
Genetic variants in Clock genes	Genetic variantes in clock genes will be determined by Illumina sytem	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epigenetic changes in clock genes	Changes in selected CpG in clock genes will be determined by Illumina system	Change from baseline to 12 weeks

Collaborators and Investigators

• Sponsor: Universidad de Granada
• Collaborators: Universidad Pública de Navarra
• Investigators: Principal Investigator: Jonatan R. Ruiz, PhD, Universidad de Granada

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2022
• Primary Completion (Actual): March 6, 2023
• Study Completion (Actual): March 6, 2023

Study Registration Dates

• First Submitted: January 17, 2022
• First Submitted That Met QC Criteria: March 25, 2022
• First Posted (Actual): April 5, 2022

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Overnutrition; Nutrition Disorders; Body Weight; Insulin Resistance; Hyperinsulinism; Obesity; Metabolic Syndrome; Overweight; Obesity, Abdominal
• Other Study ID Numbers: EXTREME

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