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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-519774-40-00 | EU Trial (CTIS) Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dietary arm | Active Comparator | Calorie restricted Mediterranean diet, with an eating window between 8AM till 6PM (early time-restricted eating) |
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| Pharmacological arm | Active Comparator | 32 mg/360 mg naltrexone/bupropion (Mysimba) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Between group difference in absoulte change in liver steatosis during six months | Measured as Controlled Attenuation Parameter (CAP) score with FibroScan. This score will range from 100 to 400 decibels per meter (dB/m). A score below 238 dB/m means the amount of fatty change in the liver is not higher than normal. | Change from baseline to 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Shift in liver fibrosis severity during six months | Liver fibrosis is categorized in fibrosis score F0, F1, F2 or F3. The scores are classified according to liver stiffness (kPa). Fibrosis score F0 and F1 means normal (no scarring), F2 means moderate scarring and F3 means severe scarring. The lower the score the better. | Change from baseline to 6 months |
Inclusion Criteria:
Exclusion Criteria:
Cisgender men and women
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| Name | Affiliation | Role |
|---|---|---|
| Manuel Castro Cabezas, Dr. | Franciscus | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Franciscus | Rotterdam | 3045 PM | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42350004 | Derived | Dietvorst CAW, Konings LAM, Saidi AN, Noordermeer T, van Wenum M, Peeters RP, Berk KA, Castro Cabezas M. 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: study protocol for a randomised controlled trial (MEDFAST trial). BMJ Open. 2026 Jun 25;16(6):e113058. doi: 10.1136/bmjopen-2025-113058. |
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All individual data will be encrypted and shared only with the research team.
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| 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. |
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| Between-group difference in weight during six months | Measured in kilograms (kg) with Seca 888 compact digital flat scale. Along with height, BMI is calculated by dividing weight by height squared. BMI should be at least 27 kg/m^2. | Change from baseline to 6 months |
| Between-group difference in height during six months | Measured in centimeters (cm) with a yardstick. Along with weight, BMI is calculated by dividing weight by height squared. BMI should be at least 27 kg/m^2. | Change from baseline to 6 months |
| Between-group difference in waist circumference during six months | Measured in centimeters (cm) with measuring tape. A healthy waist circumference for women is between 68 and 80 cm and for men between 79 and 94 cm. | Change from baseline to 6 months |
| Between-group difference in body composition during six months | Impedance, resistance and reactance are measured in Ohm at 50 kHz with bioelectrical impedance analysis (Bodystat 500). The impedance measuring range is between 20 and 1300 Ohm. | Change from baseline to 6 months |
| Between-group difference in grip strength during six months | Measured in kilograms (kg) with a hand dynamometer (Jamar). The grip strength can be measured between 0 and 90 kg. Normal values depend on gender and age. In people aged 20-29, the average grip strength is 46 kg for men and 29 kg for women. | Change from baseline to 6 months |
| Between-group difference in glycaemic regulation during six months | Glycaemic regulation is determined from values measured in the blood. These include fasting blood glucose measured in millimoles per litre (mmol/l), haemoglobin A1c (HbA1c) measured in millimoles per mole (mmol/mol) and fasting insulin measured in milligrams per decilitre (mg/dl). Normal values are below 6.1 mmol/l for fasting glucose, below 53 mmol/mol for HbA1c and between 60-110 mg/dl for fasting insulin. | Change from baseline to 6 months |
| Between-group differences in cholesterol during six months | Total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides are measured in millimoles per litre (mmol/l) through blood samples. Normal values are <5.0 mmol/l for total cholesterol, <2.6 for LDL cholesterol, >0.8 for HDL cholesterol and <2.0 for triglycerides | Change from baseline to 6 months |
| Between-group differences in lipoproteins during six months | Apolipoprotein B (ApoB), apolipoprotein AI (ApoAI), lipoprotein a (Lp(a)) and Apolipoproteïne B48 are measured in grams per litre (g/l) through blood samples. Normal values are: ApoB 0.55-1.4 g/l for men and 0.55-1.25 g/l for women; ApoAI 1.1-2.05 g/l for men and 1.25-2.15 g/l for women; Lp(a) <0.5 g/l. There are no normal values for Apolipoprotein B48 yet. | Change from baseline to 6 months |
| Between-group difference in blood pressure during six months | Systolic and diastolic blood pressure measured in millimetres of mercury pressure (mmHg). Normal values are 120-140 mmHg for systolic pressure and <90 mmHg for diastolic pressure. | Change from baseline to 6 months |
| Between-group difference in liver enzymes during six months | Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are measured in units per litre (U/L). Normal values are <50 U/L for men and <35 U/L for women for ALT and <40 U/L for men and <32 U/L for women for AST. | Change from baseline to 6 months |
| Between-group difference in renal function during six months | Renal function is determined by measuring creatinine in micromol per litre (µmol/L) and eGFR in mL/min/1.73m^2. Normal values are 62-106 µmol/L for men and 44-80 µmol/L for women for creatinine; >90 mL/min/1.73m^2 for eGFR. | Change from baseline to 6 months |
| Between-group difference in blood count during six months | Blood count is determined by thrombocytes and leukocytes in x10⁹/L. Normal values are 150-400 x10⁹/L for thrombocytes and 4.0-10.0 x10⁹/L for leukocytes. | Change from baseline to 6 months |
| Between-group difference in physical activity during six months | Physical activity will be measured with Activ8 Activity Tracker GEN2. Activity is measured in time (seconds), Metabolic equivalent (MET) and kilocalories (kcal). All for sitting, standing, walking, cycling, running and total/average. In addition, step count is also measured. | Change from baseline to 6 months |
| Between-group difference in lifestyle factors during six months | Food intake, demographic variables, drug use, smoking and drinking habits, (diabetes) medication use and compliance to the time restriction will be administered with a self-developed questionnaire | Change from baseline to 6 months |
| Between-group difference in quality of life during six months | Measured with SF-36 Questionnaire. This is a 36-item patient-reported questionnaire that covers eight health domains: physical functioning (10 items), bodily pain (2 items), role limitations due to physical health problems (4 items), role limitations due to personal or emotional problems (4 items), emotional well-being (5 items), social functioning (2 items), energy/fatigue (4 items), and general health perceptions (5 items). Scores for each domain range from 0 to 100, with a total higher score defining a more favorable health state. | Change from baseline to 6 months |
| Side effects during six months | Side effects will be self-reported | Change from baseline to 6 months |
| Drop-outs during six months | Number of participants that drop-out (categorized by reason for drop-out) | Change from baseline to 6 months |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D008103 | Liver Cirrhosis |
| D005234 | Fatty Liver |
| D050177 | Overweight |
| D009765 | Obesity |
| D006973 | Hypertension |
| D050171 | Dyslipidemias |
| D003920 | Diabetes Mellitus |
| D008107 | Liver Diseases |
| D000093763 | Intermittent Fasting |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D004066 | Digestive System Diseases |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D052439 | Lipid Metabolism Disorders |
| D005215 | Fasting |
| D005247 | Feeding Behavior |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D038441 | Diet, Mediterranean |
| D004035 | Diet Therapy |
| C000591595 | bupropion hydrochloride, naltrexone hydrochoride drug combination |
| D009271 | Naltrexone |
| D016642 | Bupropion |
| ID | Term |
|---|---|
| D000095500 | Diet, Plant-Based |
| D044623 | Nutrition Therapy |
| D013812 | Therapeutics |
| D004032 | Diet |
| D009747 | Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D009270 | Naloxone |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D011427 | Propiophenones |
| D007659 | Ketones |
| D009930 | Organic Chemicals |
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