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).

INTRODUCTION

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive condition that may lead to liver cirrhosis and hepatocellular carcinoma. It is strongly associated with cardiometabolic diseases such as type 2 diabetes (T2D) and obesity. Weight loss is a key therapeutic strategy to treat MASLD. In recent years, there has been increasing attention to weight-reducing medication, but promising dietary interventions-such as early time restricted eating (eTRE)-have also been developed. Whether these dietary interventions are a good alternative to weight-reducing medication remains unclear, as direct comparative studies are still lacking. Therefore, this study will compare the effects of an early time restricted eating Mediterranean diet (eTRE-MD) intervention with naltrexone/bupropion (N/B) treatment on liver fibrosis, measured as liver stiffness (LSM) by transient elastography, in individuals with cardiometabolic risk factors.

METHODS AND ANALYSIS: We will conduct a randomised controlled trial with a planned sample size of 70 overweight (Body mass index, BMI >27 kg/m2) adults aged 18-75 years with T2D, hypertension, dyslipidaemia or obesity and moderate to severe liver fibrosis, measured as LSM (>7.0 kPa and <13.6 kPa). The diet group will receive eTRE-MD, with a 10-hour eating time restriction (8AM-6PM). The medication group will receive 32 mg/360 mg of N/B (after a dose increase period following Summary of Product Characteristics). The main study endpoint is the between-group difference in liver fibrosis (kPa) from baseline to 6 months. Secondary endpoints are liver steatosis, weight, body composition, cardiovascular risk factors, quality of life, patient satisfaction and compliance. General linear models for repeated measurements will be applied for statistical analysis of the data.

ETHICS AND DISSEMINATION: Ethical approval from the Medical Research Ethics Committees United (MEC-U) has been obtained. The results of the study will be submitted for publication in a peer-reviewed journal.

TRIAL REGISTRATION NUMBER: NCT06845345.