An Intervention Study of Compound Silymarin in Patients With Non-alcoholic Fatty Liver Disease

Study Overview
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Brief Summary
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Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disorder in China. The aim of this project is to evaluate the effects of compound silymarin on biomarkers of lipid metabolism and inflammation in the patients with NAFLD.

Detailed Description
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Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disorder in China but still has no exact therapy for this disease instead of improving our diet and enhancing physical activity. Silymarin is a mixture of flavonoids extracted from seeds of Silybum marianum or milk thistle, and its major active compound is silibinin. Because of its antioxidant, anti-inflammatory and antifibrotic power, silymarin has important biological effects in NAFLD. Furthermore, some traditional liver protective Chinese medicines are also helpful in controlling the progression of NAFLD, such as pueraria, schisandra and salvia miltiorrhiza. At present, there are few reports on the combination of silymarin and these traditional Chinese medicines in the treatment of NAFLD. This study aims to test the effect of compound silymarin on laboratory markers and clinical evolution of patients with NAFLD.

Official Title
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Effects of Compound Silymarin on Biomarkers of Lipid Metabolism and Inflammation in Patients With Non-alcoholic Fatty Liver Disease: A Randomized Controlled Double-blind Trial

Conditions
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Nonalcoholic Fatty Liver Disease

Intervention / Treatment
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* Dietary Supplement: Silibinin extract, mixed power of pueraria, schisandra and salvia miltiorrhiza
* Dietary Supplement: Silibinin extract
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject's BMI is ≥ 22.0 kg/m2 and < 33.0 kg/m2; Subject is diagnosed with NAFLD according to the Chinese Non-alcoholic fatty liver disease prevention guide 2018; A mildly elevated of ALT level (≥ 30 U/L for male, ≥ 19 U/L for female) or an AST/ALT ratio < 1.0; Must be able to swallow tablets. Exclusion Criteria: ≥ 30 grams of alcohol/day for male and ≥ 20 grams of alcohol/day for female; Patients with certain hepatic diseases such as gallstones, hepatitis C, autoimmune hepatitis, and hepatolenticular degeneration which can lead to fatty liver disease; Be taking medicines or supplements that would influence the liver function, lipid metabolism; Patients with total parenteral nutrition, inflammatory bowel disease, celiac disease, hypothyroidism, Cushing syndrome, Mauriac syndrome, etc; Patients with hereditary diseases, coronary heart disease, mental disorder, cancer, cirrhosis and renal disease; Body weight change are more than 10% in previous 3 months; Patients who have participated in or are participating in other clinical trials within 3 months of their first administration of the study product; Subjects are allergic to the ingredients in the test or control samples; Woman who is pregnant or breastfeeding; Subjects cannot meet the requirements of compliance in the pre-experiment period; Subjects who fail to sign the informed consent forms.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Compound silymarin<br>Dietary supplement: 4 tablets of compound silymarin twice a day for 12 weeks The active ingredient in each tablet: 81.6 mg of silibinin, mixed power of pueraria, schisandra and salvia miltiorrhiza | Dietary Supplement: Silibinin extract, mixed power of pueraria, schisandra and salvia miltiorrhiza<br>* Take 4 tablets with warm water twice a day<br>|
| Active Comparator: Silymarin<br>Dietary supplement: 4 tablets of silymarin twice a day for 12 weeks The active ingredient in each tablet: 81.6 mg of silibinin | Dietary Supplement: Silibinin extract<br>* Take 4 tablets with warm water twice a day<br>|
| Placebo Comparator: Placebo<br>Dietary supplement: 4 tablet of placebo twice a day for 12 weeks Placebo Composition: corn dextrin | Dietary Supplement: Placebo<br>* Take 4 tablets with warm water twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver enzymes | Serum activities of alanine transaminase (ALT) and aspartate transaminase (AST) | Change from baseline ALT and AST at 12 weeks | 
| Lipid profile | Serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) | Change from baseline lipid profile at 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| T-Lymphocytes' composition | Changes of T-Lymphocytes' composition in peripheral blood | Change from baseline T-Lymphocytes' composition at 12 weeks | 
| Bile acid metabolism | Composition of serum and fecal bile acids | Change from baseline composition of serum and fecal bile acids at 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nonalcoholic fatty liver disease, Silymarin, Inflammation, Lipid metabolism