Effect of essential phospholipids on hepatic steatosis in metabolic dysfunction-associated steatotic liver disease associated with type 2 diabetes mellitus and/or hyperlipidemia and/or obesity: study protocol of a randomized, double-blind, phase IV clinical trial

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a predominant chronic liver condition globally and is strongly associated with obesity, diabetes mellitus, and dyslipidemia. Essential phospholipids (EPL) are recommended as supportive treatment for managing liver conditions, including MASLD or metabolic dysfunction-associated steatohepatitis, cirrhosis, and viral hepatitis. While efficacy of EPL as an adjunctive therapy in MASLD treatment has been established earlier, certain aspects of its usage such as the impact of standard-of-care parameters, effect of EPL on quality of life (QoL) and change in symptoms evaluation in patients with MASLD remain unexplored. The proposed trial aims to assess the efficacy and safety of EPL and the subsequent QoL of patients with MASLD associated with type 2 diabetes mellitus (T2DM) and/or hyperlipidemia and/or obesity. Methods This is a multicenter, multinational, double-blind, randomized, two-arm, placebo-controlled, parallel-group, phase IV clinical trial. The trial is being conducted in approximately 190 patients who are randomized on a 1:1 basis either to the EPL arm (Essentiale® 1800 mg/day orally + standard of care) or placebo arm (placebo + standard of care). The primary outcome is to assess the efficacy of EPL on hepatic steatosis, as measured by transient elastography, from baseline to 6 months. The secondary outcomes include change in QoL parameters, as measured by the Chronic Liver Disease Questionnaire–metabolic dysfunction-associated steatotic liver disease/ metabolic dysfunction-associated steatohepatitis and change in symptom evaluation (using the Global Overall Symptom scale) from baseline to 6 months for symptoms, including asthenia, feeling depressed, abdominal pain/discomfort, or fatigue. Discussion The current protocol design will allow to comprehensively explore the efficacy of EPL added to the standard of care on hepatic steatosis and QoL and its safety in patients with MASLD associated with T2DM and/or hyperlipidemia and/or obesity by assessing various outcome measures. Trial registration European Union Clinical Trials Register, EudraCT, 2021–006069-39. Registered on March 13, 2022.