Effect of an Early Time Restricted Eating Mediterranean Diet Compared to Naltrexone/Bupropion on Liver Fibrosis in People With Cardiometabolic Risk Factors in a Hospital Outpatient Clinic (MEDFAST-study)

NCT06845345 | Enrolling By Invitation Phase 4

• 1 other identifier: 2024-519774-40-00
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

In the Netherlands, there are many people with cardiometabolic diseases. More than half of these people also have fatty liver. This is a build-up of fat in the liver (steatosis) and can lead to long-term scarring (fibrosis) and even death of the liver. Losing weight can help reduce this. Losing weight can be done with medication such as naltrexone/bupropion, which is often prescribed to people with cardiometabolic diseases, but losing weight can also be done with diet. In this study, the investigators want to combine a Mediterranean diet (with lots of vegetables, fruits, whole grain products, nuts and olive oil) with intermittent fasting. In addition participants are not allowed to eat after the evening meal. The investigators will compare this with a group of participants receiving naltrexone/bupropion, to see if a diet with intermittent fasting might be better for reducing liver steatosis and fibrosis in people with cardiometabolic diseases.

Conditions

Liver Fibrosis; Liver Steatoses; Hepatic Steatosis; Cardio-metabolic Risk; Cardio-metabolic Health; Hypertension; Diabetes Mellitus, Type 2; MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease; Hepatic Fibrosis; Overweight or Obesity; MASLD; Dyslipidaemia

Keywords

diabetes; liver diseases; liver fibrosis; intermittent fasting; mediterranean diet; mysimba; lifestyle; cardiometabolic diseases; obesity

Outcome Measures

Primary Outcomes (1)

• Between-group difference in absolute change in liver fibrosis during six months

  Measured as liver stiffness in kilopascals (kPa) by transient elastography with FibroScan. For a value between 0 and 8 kPa, no liver fibrosis is assumed. Anything above 8 kPa means liver fibrosis. The highest possible result is 75 kPa.

  Change from baseline to 6 months

Secondary Outcomes (16)

• Between group difference in absoulte change in liver steatosis during six months

  Change from baseline to 6 months

• Between-group difference in weight during six months

  Change from baseline to 6 months

• Between-group difference in height during six months

  Change from baseline to 6 months

• Between-group difference in waist circumference during six months

  Change from baseline to 6 months

• Between-group difference in body composition during six months

  Change from baseline to 6 months

Other Outcomes (3)

• Shift in liver fibrosis severity during six months

  Change from baseline to 6 months

• Side effects during six months

  Change from baseline to 6 months

• Drop-outs during six months

  Change from baseline to 6 months

Study Arms (2)

Dietary arm

ACTIVE COMPARATOR

Calorie restricted Mediterranean diet, with an eating window between 8AM till 6PM (early time-restricted eating)

Other: early time restricted Mediterranean diet

Pharmacological arm

ACTIVE COMPARATOR

32 mg/360 mg naltrexone/bupropion (Mysimba)

Drug: Mysimba

Interventions

Mysimba DRUG

Participants will take Mysimba twice daily at a total dose of 32 mg/360 mg naltrexone/bupropion per day for a duration of six months. The dosage will be built up in the first month following the stepped care approach used in the Summary of Product Characteristics (SmPC), up to maximally tolerated doses. Compliance with N/B intake is monitored by pill counting at the three and six-month visits. Participants receive usual care, including the advice of 60 minutes of exercise per day and standard dietary recommendations according to the guidelines for the Dutch population.

Also known as: naltrexone/bupropion, pharmacological intervention

Pharmacological arm

early time restricted Mediterranean diet OTHER

Participants will start with a calorie restricted Mediterranean diet, with an eating window between 8AM till 6PM (early time-restricted eating) for a period of six months. Participants are asked to stop eating at 6PM. This results in a daily fasting window of approximately 14 hours. A daily calorie restriction of 500 kcal will be applied, based on the estimated energy requirement calculated using the WHO equation for participants with a BMI ≤ 30 and the Harris-Benedict equation for those with a BMI \> 30.

Also known as: early time restricted eating, mediterranean diet, intermittent fasting, dietary intervention

Dietary arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Gender Eligibility Details: Cisgender men and women
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI \> 30 kg/m2 or BMI \> 27 kg/m2 and at least one cardiometabolic risk factor (T2D, hypertension, dyslipidaemia)
• Moderate to severe liver fibrosis, measured as liver stiffness by transient elastography (LSM \> 7.0 kPa and \< 13.6 kPa)
• Aged 18-75 years
• Written informed consent

You may not qualify if:

• An insufficient comprehension of the Dutch language (spoken and written)
• Female who is pregnant, breast-feeding or intends to become pregnant
• Participants with an established diagnosis of liver pathology like, but not limited to: Hepatitis B, Hepatitis C, Autoimmune hepatitis, Wilson's disease, Hemochromatosis, Primary biliary cholangitis, Primary sclerosing cholangitis, Alcoholic liver disease
• History of liver transplant, or current placement on a liver transplant list
• History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy or variceal bleeding
• Participants with active HIV infection and/or treatment
• Participants with diagnosed malignancies with or without active treatment
• Participants with history or pre-existing renal disease (eGFR \<30 mL/min/1.73 m2)
• Participants with corticosteroid induced diabetes (while still using corticosteroids)
• Participants using GLP-1 agonists for less than 3 months or not yet on a stable dose
• Participants using MAO-inhibitors, opioids and/or methadone (due to contraindication)
• Known or suspected excessive alcohol consumption (\>30 grams/day for males or \>20 grams/day for females. One drink is equivalent to 10 grams of alcohol)
• Previous or planned (during the trial period) obesity treatment with surgery. However, previous interventions that, due to reversal or removal, do not have any influence on the patient's weight, in the opinion of the investigator, are allowed.
• Participants with a history or evidence of any other clinically significant condition or planned or expected procedure that in the opinion of the investigator, may compromise the patient's safety or ability to complete the study

Sponsors & Collaborators

• Carmen Dietvorst: lead

Study Sites (1)

Franciscus

Rotterdam, 3045 PM, Netherlands

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Liver Cirrhosis; Fatty Liver; Overweight; Obesity; Hypertension; Dyslipidemias; Diabetes Mellitus; Liver Diseases; Intermittent Fasting

Interventions

Diet, Mediterranean; Diet Therapy; bupropion hydrochloride, naltrexone hydrochoride drug combination; Naltrexone; Bupropion

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Lipid Metabolism Disorders; Fasting; Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Diet, Plant-Based; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Propiophenones; Ketones; Organic Chemicals

Study Officials

• Manuel Castro Cabezas, Dr.

  Franciscus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MSc.

Study Record Dates

• First Submitted: February 17, 2025
• First Posted: February 25, 2025
• Study Start: April 14, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)