The Effect of Time-restricted Eating on Liver Metabolism (TREL)

Numerous studies have established the role of nutrition on obesity and its related metabolic diseases, which together affect a billion individuals worldwide. Evidence indicate that meal timing regulates numerous metabolic processes suggesting that meal time manipulation may be a simple intervention against obesity and its metabolic diseases. Time-restricted eating (TRE) is a dietary manipulation that involves restricting food intake to 6-10 h/day with no energy intake the rest of the day. In rodents, TRE significantly decreases hepatic steatosis and dyslipidemia, while it supports a healthier hepatic cellular content even without caloric restriction, potentially by alternating activation of nutrient sensing mechanisms and effects on circadian oscillations. However, an understanding of the effect of TRE on liver health in people is not clear. Accordingly, we will conduct a randomized controlled trial in people with overweight/obesity and hepatic steatosis to determine the effect of 9 h TRE for 12 weeks, on key metabolic outcomes in liver health: 1) intrahepatic triglyceride content using magnetic resonance imaging; 2) de novo lipogenesis during fasting and postprandial conditions using administration of deuterated water in conjunction with mathematical modeling. The proposed study will enable us to determine the effect of meal timing on metabolic function in people with NAFLD.

Study Overview

• Status: Completed
• Conditions: Obesity; NAFLD; Nutritional and Metabolic Diseases
• Intervention / Treatment: Behavioral: Time restricted eating

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Davis, California, United States, 95616-5398
      • University of California, Davis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age 25-75 years
• men and women
• body mass index 25-45 kg/m2
• clinical diagnosis of NAFLD
• self-reported habitual eating period more than or equal to 14 h per day.

Exclusion Criteria:

• shift worker, recent or expected travel crossing time zones

• fasting >12-h/day more than once a week

  *> once a week no food intake after 18:00

• habitually waking up before 04:00 and sleeping before 22:30
• unstable weight (>5% change in the last 2 months)
• diabetes mellitus or alcoholic liver disease
• sleep disorder
• history of or current eating disorder
• cancer in last 5 years
• conditions that render subject unable to complete all testing procedures
• use of medications that affect the study outcome measures or increase the risk of study procedures and that cannot be temporarily discontinued
• smoking or illegal drug use
• pregnant or breastfeeding
• having metals in the body
• cognitive impairment
• gastrointestinal or bariatric surgery that affects nutrient digestion and absorption unable to grant voluntary informed consent or comply with the study instructions individuals who are not yet adults (infants, children, teenagers)
• individuals that are unable to lie motionless on the MRI scanner for an hour or *have tattoos or tattooed eyeliner
• alcohol abuse
• prisoners

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Subjects will consume all meals/snacks during a ~15-h daily eating period (~9-h fasting). The prescribed energy intake will be monitored and adjusted as needed to achieve weight maintenance.
Experimental: TRE isocaloric; Subjects will consume all meals/snacks during a ~9-h daily eating period (~15-h fasting). The prescribed energy intake will be monitored and adjusted as needed to achieve weight maintenance.	Behavioral: Time restricted eating; Participants will be asked consume all meals/snacks during a ~9-h daily eating period (~15-h fasting).
Experimental: TRE ad libitum; Subjects will consume all meals/snacks during a ~9-h daily eating period (~15-h fasting) without any other dietary advice.	Behavioral: Time restricted eating; Participants will be asked consume all meals/snacks during a ~9-h daily eating period (~15-h fasting).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Intrahepatic triglyceride (IHTG) content	IHTG will be assessed by using MRI	About 12 weeks
Change in de novo lipogenesis (DNL)	DNL will be assessed by using administration of deuterated water and measurement of deuterium enrichment in plasma lipids	About 12 weeks
Change in glucose, free fatty acid and triglyceride levels in response to a meal	Postprandial metabolic homeostasis will be assessed by using a mixed meal tolerance test.	Before and after 12 weeks

Collaborators and Investigators

• Sponsor: University of California, Davis

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2021
• Primary Completion (Actual): March 7, 2024
• Study Completion (Actual): March 7, 2024

Study Registration Dates

• First Submitted: July 20, 2021
• First Submitted That Met QC Criteria: August 2, 2021
• First Posted (Actual): August 9, 2021

Study Record Updates

• Last Update Posted (Estimated): November 25, 2024
• Last Update Submitted That Met QC Criteria: November 21, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases
• Other Study ID Numbers: 1757716

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