Efficacy of silymarin in patients with Non-Alcoholic Fatty Liver Disease – The Siliver trial: a study protocol for a randomized controlled clinical trial

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the most prevalent liver diseases globally. Pharmacological treatments for NAFLD are still limited. Silymarin, a compound extracted from Silybum marianum, is an herbal supplement traditionally used in folk medicine for liver disorders. It has been proposed that silymarin may possess hepatoprotective and anti-inflammatory properties. The present trial aims to assess the efficacy of silymarin supplementation in the adjuvant treatment of NAFLD in adult patients.
Method: This is a randomized double-blind placebo-controlled clinical trial recruiting adult NAFLD patients in therapy on an outpatient basis. Participants are randomized to an Intervention (I) or Control (C) group. Both groups receive identical capsules and are followed for 12 weeks. I receives 700mg of silymarin + 8mg vitamin E + 50mg phosphatidylcholine daily, whilst C receives 700mg maltodextrin + 8mg vitamin E + 50mg phosphatidylcholine daily. Patients undergo a computerized tomography (CT) scan and blood tests at the beginning and end of the study. Monthly face-to-face consultations and weekly telephone contact are carried out for all participants. The primary outcome assessed will be change in NAFLD stage, if any, assessed by the difference in attenuation coefficient between liver and spleen, obtained by upper abdomen CT.
Discussion: The results of this study may provide a valuable opinion on whether silymarin can be used as adjuvant therapy for the management or treatment of NAFLD. The data presented on efficacy and safety of silymarin may provide more foundation for further trials and for a possible use in clinical practice.
Trial registration: This study has been approved by the Research Ethics Committee of the Professor Edgard Santos University Hospital Complex, Salvador BA, Brazil, under protocol 2.635.954. The study is carried out according to guidelines and regulatory standards for research involving humans, as set out in Brazilian legislation. Trial registration - clinicaltrials.gov: NCT03749070.