D-Limonene for regulating metabolism-associated fatty liver disease (MAFLD) and analysis of the TCM constitution: A protocol for an exploratory, randomized, double-blind, placebo-controlled trial (DL-MAFLD-TCM)

The protocol describes the first study evaluating the treatment of metabolism-associated fatty liver disease (MAFLD). MAFLD, formerly known as nonalcoholic fatty liver disease, was renamed by an internationally renowned liver disease expert group in 2020. MAFLD contains three types: overweight/obesity (A type), type 2 diabetes mellitus (B type), or evidence of metabolic dysregulation (C type). There is a lack of effective therapeutic drugs. We found that D-limonene, a food additive in China, has potential activity on the A type of MAFLD through animal studies. Then, we designed an exploratory, single-center, double-blind, placebo-controlled, randomized clinical trial for the evaluation of limonene capsules (marketed product in China) on regulating A type of MAFLD and analysis of the TCM constitution (DLMAFLD-TCM). A total of 60 patients with A type of MAFLD will be randomly assigned to a treatment arm with (n = 30) or without (n = 30) Food Frontiers for Review Only limonene (placebo) for 12 weeks. The primary end point will be assessed at two end points combined for A type: changes in the controlled attenuation parameter and body mass index at baseline and 12 weeks after administration. The study procedures and informed consent form were approved by the hospital. We detail the protocol and the statistical analysis plan of the trial prior to study completion, which is for further study. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2000035888).