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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
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.
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.
Franciscus
Rotterdam, Netherlands
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.
Time frame: Change from baseline to 6 months
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.
Time frame: Change from baseline to 6 months
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: Change from baseline to 6 months
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