Effects of Tablets of Silybum Marianum, Pueraria Lobate and Salvia Miltiorrhiza on Fatty Liver

Study Overview
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Brief Summary
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Objectives: To examine the effects of tablets of silybum marianum, Pueraria lobate and salvia miltiorrhiza on the progression of fatty liver in patients with fatty liver. Design: a double-blinded randomized placebo-controlled clinical trial. Setting: community residents, Guangzhou city, South China. Participants: a total 118 men and women (18-65 years), with BMI range of 24-30 kg/m2, and with fatty liver screened by ultrasound or MR at baseline. Arms and Interventions: 118 participants were randomly allocated into two arms using a block randomization method. Experimental Arm: tablet of silybum marianum, Pueraria lobate and salvia miltiorrhiza, 3 tablets (1g each) twice a day for 6 months; Placebo Arm: placebo tablets, 3 tablets (1g each) twice a day for 6 months. Outcome Measures: determined at baseline and at 6 months post treatment Primary Outcome Measures: 1) proton density fat fraction of liver assessed by MR; 2) serum liver fibrosis biomarkers: type procollagen III N terminal peptide, hyaluronic acid, laminin, collagen type IV, and glycocholic acid; 3) NAFLD fibrosis score. Secondary Outcome Measures: 1) serum liver function biomarkers: AST, ALT, GGT, ALP, total protein, and bile acids; 2) fasting blood lipids: total triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol; 3) fasting serum glucose and insulin; 4) serum inflammatory factors (hsCRP and IL-6); 5) oxidative stress: SOD and MDA; and 6) body measurements and body fat mass. Data Analyses: Mean changes in the above outcome measures from baseline to 6 months will be compared between the two arms.

Official Title
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Effects of Tablets of Silybum Marianum, Pueraria Lobate and Salvia Miltiorrhiza on the Progression of Fatty Liver in Adults: a Double-blinded Randomized Placebo-controlled Clinical Trial

Conditions
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Fatty Liver Disease

Intervention / Treatment
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* Dietary Supplement: Tablet of silybum marianum, Pueraria lobate and salvia miltiorrhiza
* Other: Placebo tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-65 years BMI: 24-30 kg/m2 Fatty liver, assessed by ultrasound or MR Had normal diet and normal daily life. Exclusion Criteria: Hospital confirmed diseases of heart, liver (viral hepatitis, drug-induced liver injury, cirrhosis), kidney, brain, hematopoietic system，diabetes, immune system, and cancer； Taking medicine or supplements known to affect fatty liver, body fat; Body weight had changed more than 10% within the past 3 months; Physical or mental disabled to participate the trial; Compliance of tablet consumption is/was less than 80% in run-in period; Pregnant or lactating women, or intended pregnancy during the trial period; Be allergic to the proposed supplements； Attended or plan to attend other trial(s); Be unwell to sign the informed consent form, or have other conditions that be not suitable to attend the trial considered by the investigators.

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>Tablet name: tablet of silybum marianum, Pueraria lobate and salvia miltiorrhiza; Dosage: 1g/tablet, 3 tablets/time； Frequency: 2 times/day; Duration: 6 months | Dietary Supplement: Tablet of silybum marianum, Pueraria lobate and salvia miltiorrhiza<br>* Brand names: BY-HEALTH； Main contents (per 100g): silibinin 2g, salvianolic acid B 0.72g，Puerarin 0.68g<br>|
| Placebo Comparator: Control group<br>Tablet name: Placebo; Dosage: 1g/tablet, 3 tablets/time； Frequency: 2 times/day; Duration: 6 months | Other: Placebo tablet<br>* Brand names: BY-HEALTH； Main contents : starch<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline proton density fat fraction of liver at 6 months | Proton density fat fraction of liver: measured using magnetic resonance (MR) | 0 and 6 months | 
| Change from baseline liver fibrosis biomarker (Type pro-collagen III N terminal peptide) at 6 months | Liver fibrosis biomarker 1: Type pro-collagen III N terminal peptide | 0 and 6 months | 
| Change from baseline liver fibrosis biomarker (hyaluronic acid) at 6 months | Liver fibrosis biomarker 2: hyaluronic acid | 0 and 6 months | 
| Change from baseline liver fibrosis biomarker (laminin) at 6 months | Liver fibrosis biomarker 3: laminin | 0 and 6 months | 
| Change from baseline liver fibrosis biomarker (collagen type IV) at 6 months | Liver fibrosis biomarker 4: Collagen type IV | 0 and 6 months | 
| Change from baseline liver fibrosis biomarker (glycocholic acid) at 6 months | Liver fibrosis biomarker 5: Glycocholic acid | 0 and 6 months | 
| Change from baseline NAFLD fibrosis score at 6 months | NAFLD fibrosis score: = -1.675 + 0.037 Age (yrs) + 0.094 BMI (kg/m2) + 1.13 impaired fasting glucose (IFG)/diabetes (yes = 1, no = 0) + 0.99 AST/ALT ratio - 0.013Platelet (*10E9/L) - 0.66 Albumin (g/dl) | 0 and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline liver function biomarker (AST) at 6 months | Liver function biomarkers 1: AST | 0 and 6 months | 
| Change from baseline liver function biomarker (ALT) at 6 months | Liver function biomarkers 2: serum ALT | 0 and 6 months | 
| Change from baseline liver function biomarker (GGT) at 6 months | Liver function biomarkers 3: serum gamma-glutamyl transpeptidase (GGT) | 0 and 6 months | 
| Change from baseline liver function biomarker (total protein) at 6 months | Liver function biomarkers 4: serum total protein | 0 and 6 months | 
| Change from baseline liver function biomarker (ALP) at 6 months | Liver function biomarkers 5: serum alkaline phosphatase (ALP) | 0 and 6 months | 
| Change from baseline liver function biomarker (bile acids) at 6 months | Liver function biomarkers 6: serum bile acids | 0 and 6 months | 
| Change from baseline fasting blood lipid (TG) at 6 months | Fasting blood lipid 1: serum triglycerides | 0 and 6 months | 
| Change from baseline fasting blood lipid (TC) at 6 months | Fasting blood lipid 2: serum total cholesterol | 0 and 6 months | 
| Change from baseline fasting blood lipid (HDL-C) at 6 months | Fasting blood lipid 3: serum high-density lipoprotein cholesterol (HDL-C) | 0 and 6 months | 
| Change from baseline fasting blood lipid (LDL-C) at 6 months | Fasting blood lipid 4: serum low-density lipoprotein cholesterol (LDL-C) | 0 and 6 months | 
| Change from baseline fasting blood glucose at 6 months | Fasting blood glucose: serum glucose | 0 and 6 months | 
| Change from baseline fasting blood insulin at 6 months | Fasting blood insulin: serum insulin | 0 and 6 months | 
| Change from baseline systolic blood pressure at 6 months | Blood pressure: systolic blood pressure | 0 and 6 months | 
| Change from baseline diastolic blood pressure at 6 months | Blood pressure: diastolic blood pressure | 0 and 6 months | 
| Change from baseline Inflammatory factor (hsCRP ) at 6 months | Inflammatory factor 1: serum high sensitivity C reactive protein (hsCRP) | 0 and 6 months | 
| Change from baseline Inflammatory factor (IL-6) at 6 months | Inflammatory factor 2: serum IL-6 | 0 and 6 months | 
| Change from baseline oxidative stress (SOD) at 6 months | Oxidative stress biomarker 1: serum SOD | 0 and 6 months | 
| Change from baseline oxidative stress (MDA) at 6 months | Oxidative stress biomarker 2: serum malondialdehyde (MDA) | 0 and 6 months | 
| Change from baseline fat mass at 6 months | Fat mass (FM): FM (kg) at total body and sub-regions determined by a dual energy x-ray absorptiometry (DXA) | 0 and 6 months | 
| Change from baseline percentage fat mass at 6 months | Percentage Fat mass (%FM): %FM (%) at total body and sub-regions determined by DXA | 0 and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fatty liver, silybum marianum, Pueraria lobate, salvia miltiorrhiza