Chrononutrition/ Chronotoxicity Intervention in People With Metabolic-associated Steatotic Liver Disease.

NCT06705868 | Not Yet Recruiting

• 1 other identifier: CHRONOMASLD
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to study the effect of a time-restricted eating (TRE) dietary pattern combined with a time of consumption restriction about the daily portions of fruits and vegetables in people diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD). The protocol of the study is an intention to treat protocol. The main research questions are:

1. 1.Does compliance in a TRE dietary scheme (positively) affect changes in body weight and body fat mass in people diagnosed with MASLD?
2. 2.Does an additional time restriction on the consumption of fruits and vegetables within the "light-window" of the day affects the metabolism of food contaminants?
3. 3.Adhere to a TRE dietary pattern for 3 months. TRE consists of an 8-hour eating vs 16 hours fasting within the day. First meal of the day should not occur at least an hour after wake-up time and last meal of the day should occur not later than 2 hours before bed-time.
4. 4.Adhere to a further time restricted consumption of a "5-a-day" portions of fruits and vegetables between the "light-window hours" between 9am to 4pm.
5. 5.Visit the Nutrition \& Dietetics Clinic once every month for anthropometric measurements (on 4 time points).
6. 6.Collect and deliver first morning urine samples (on 7 time points).
7. 7.Collect and deliver saliva samples at baseline and at the end of the trial (Saliva collection should occur every 4-hours for 48-hours including fasting collection at baseline and at the end of three months)

Conditions

MASLD; MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease; NAFLD; NAFLD (Nonalcoholic Fatty Liver Disease)

Keywords

non alcoholic fatty liver disease (NAFLD); chrononutrition; intermittent fasting; randomized controlled trial (RCT); chronotoxicity; time restricted eating; MASLD; Metabolic Dysfunction-Associated Steatotic Liver Disease

Outcome Measures

Primary Outcomes (2)

• Changes in body weight

  Changes in body weight (in kilograms) from baseline to the end of intervention in the TRE and the Soc group (intervention vs control, respectively). Depending on the data distribution, independent samples t-test or Wilcoxon Rank-Sum Test will be used If the changes do or do not follow a normal distribution between baseline and post-treatment are normally distributed, respectively. Mixed Effect Models will be used to assess the main and interaction (included if p\<0.05) effects between groups and time since study initiation adjusting for confounders, including circadian rhythm metrics such as melatonin and/or cortisol.

  From enrolment to the end of treatment at 3 months (with two in-between measurement)

• Changes in body fat mass

  Changes in body fat mass (expressed as % of the total body weight in kilograms) from baseline to the end of intervention in the TRE and the Soc group (intervention vs control, respectively). Depending on the data distribution, independent samples t-test or Wilcoxon Rank-Sum Test will be used If the changes do or do not follow a normal distribution between baseline and post-treatment are normally distributed, respectively. Mixed Effect Models will be used to assess the main and interaction (included only if p\<0.05) effects between groups and time since study initiation adjusting for confounders, including circadian rhythm metrics such as melatonin and/or cortisol.

  From enrolment to the end of treatment at 3 months (with one in-between measurement)

Secondary Outcomes (12)

• Changes in Pesticide Metabolite 3-phenoxybenzoic Acid (3-PBA) Levels in Urine

  From first day of the intervention to the end of treatment at 3 months (with six in between measurements)

• Changes in Pesticide Metabolite 6-chloronicotininc Acid (6-CN) Levels in Urine

  From first day of the intervention to the end of treatment at 3 months (with six in between measurements)

• Changes in waist circumference (WC)

  From enrolment to the end of treatment at 3 months (with one in-between measurement)

• Changes in 4-Hydroxynonenal (4HNE) Levels in Urine

  From first day of the intervention to the end of treatment at 3 months (with six in between measurements)

• Changes in Body Mass Index (BMI)

  From enrolment to the end of treatment at 3 months (with two in-between measurement)

Other Outcomes (3)

• Changes in other pesticide biomarkers in urine

  From first day o the intervention to the end of treatment at 3 months (with six in between measurements)

• Changes in other biomarkers of oxidative stress in urine

  From first day o the intervention to the end of treatment at 3 months (with six in between measurements)

• Changes in metabolome in saliva and urine

  From first day o the intervention to the end of treatment at 3 months (with six in between measurements)

Study Arms (2)

Standard of Care (Group A-Control)

OTHER

Participants in Group A will follow a Standard of Care Intervention. They will receive guidance on a) energy restriction, b) weight reduction, c) the macronutrient composition of the diet, d) limitation of alcohol intake (below the risk threshold of 30g/d and 20g/day for men and women, respectively) and e) increase their physical activity levels. Additionally, in this study patients will be asked to consume the general recommendation of "5-a-day" as part of their dietary healthier behaviour. Moreover, participants should stay well hydrated and get adequate of sleep (an average of 6 consecutive hours at night). Oral and written guidance for the management of MASLD will be administered. The duration of the intervention is 3 months.

Other: Lifestyle Management

Time-restricted eating (Group B-Intervention)

EXPERIMENTAL

Participants will have to adhere to an ad libitum TRE dietary pattern (8 hours eating, 16 hours fasting) with an additional dietary restriction regarding the "5-a-day" fruit and vegetable in which they will need to be consumed between 9am-4pm. Some more restrictions regarding first and last meal will be asked. Participants will be instructed that their first meal of the day should not start for at least an hour after wake-up hour and will also be asked to have their last meal at least 2 hours earlier than bedtime (actual time of sleep). The duration of the intervention is 3 months.

Other: Diet-Time-restricted eating (TRE)

Interventions

Diet-Time-restricted eating (TRE) OTHER

Ad libitum time-restricted scheme with a further time-restriction on fruit and vegetable consumption in participants with MASLD

Time-restricted eating (Group B-Intervention)

Lifestyle Management OTHER

The SoC intervention refers to an adaptation of a healthier lifestyle in elements that have to do with weight management, adopting healthier dietary habits, alcohol intake reduction, increase physical activity levels, in people diagnosed with MASLD.

Standard of Care (Group A-Control)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body mass index 25 (±0,5)-45(±0,5) kg/m2
• Clinical diagnosis of MASLD, not excluding undiagnosed NASH or with NASH stage F0-F1
• Self-reported habitual eating period more than or equal to 14 h per day, BUT NOT LESS.
• Cyprus inhabitants of for at least 1 year
• Registered to the National Health System of the Republic of Cyprus (Gesy

You may not qualify if:

• Night Shift worker
• Fasting \>12-h/day more than once a week or \> once a week no food intake after 18:00
• Co-existing causes of chronic liver disease according to standard diagnostic testing including, but not restricted to:
• Positive hepatitis B surface antigen
• Positive hepatitis C virus RNA
• Suspicion of drug-induced liver disease
• Alcoholic liver disease
• Autoimmune hepatitis
• Wilson's disease
• Hemochromatosis
• Primary biliary cholangitis or primary sclerosing cholangitis
• Known or suspected hepatocellular carcinoma
• Medications which cause liver disease or secondary hepatic steatosis (Tamoxifen, systemic corticosteroids, methotrexate, tetracycline, estrogens, valproic acid, and statin (registration is possible if statin is delivered in a consistent dosage within 12 weeks)
• Current or recent history (\<5 years) of significant alcohol intake (\>30g of alcohol/ day or \>210g/week for men, \>20g of alcohol/day or \>140g/week for women)
• Doctor diagnosed diabetes mellitus on insulin or sulfonylureas

Sponsors & Collaborators

• Cyprus University of Technology: lead
• Cyprus State Heath Organization Services: collaborator

Study Sites (1)

Limassol General Hospital

Limassol, 4159, Cyprus

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Intermittent Fasting

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Fasting; Feeding Behavior; Behavior

Central Study Contacts

Konstantinos C. Makris, Professor

CONTACT

0035725002398; konstantinos.makris@cut.ac.cy

Elina I Ioannou

CONTACT

elii.ioannou@edu.cut.ac.cy

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Environmental Health

Study Record Dates

• First Submitted: November 23, 2024
• First Posted: November 26, 2024
• Study Start: January 5, 2026
• Primary Completion (Estimated): December 15, 2027
• Study Completion (Estimated): December 15, 2029
• Last Updated: November 19, 2025

Record last verified: 2025-11

Locations

CY (1)