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

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

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

1. 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.
2. 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: Tablet of silybum marianum, Pueraria lobate and salvia miltiorrhiza; Other: Placebo tablet

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; 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; Brand names: BY-HEALTH； Main contents (per 100g): silibinin 2g, salvianolic acid B 0.72g，Puerarin 0.68g
Placebo Comparator: Control group; Tablet name: Placebo; Dosage: 1g/tablet, 3 tablets/time； Frequency: 2 times/day; Duration: 6 months	Other: Placebo tablet; Brand names: BY-HEALTH； Main contents : starch

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline body weight at 6 months	Body measurement 1: Body weight (in kg)	0 and 6 months
Change from baseline body height at 6 months	Body measurement 2: Body height (in cm)	0 and 6 months
Change from baseline waist circumference at 6 months	Body measurement 3: Waist circumference (in cm)	0 and 6 months
Change from baseline hip circumference at 6 months	Body measurement 4: hip circumference (in cm)	0 and 6 months
Change from baseline anxiety score at 6 months	Anxiety Score: assessed by a Self Rating Anxiety Scale (SAS).the minimum and maximum values: 25-100 points. Higher scores mean worse outcome.	0 and 6 months
Number of treated events related to supplements between baseline to 6 months	Adverse/side effects: Assessed by using questionnaire of medical history, medication use, symptoms.	0 and 6 months
Percentage of the interventional supplements consumed between baseline to 6 months	Compliance assessment: Assessed by counting the number of remaining supplemental tablets at 6 months	at 6 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Anticipated): December 30, 2021
• Study Completion (Anticipated): June 30, 2022

Study Registration Dates

• First Submitted: September 10, 2021
• First Submitted That Met QC Criteria: September 29, 2021
• First Posted (Actual): October 13, 2021

Study Record Updates

• Last Update Posted (Actual): October 13, 2021
• Last Update Submitted That Met QC Criteria: September 29, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: fatty liver; silybum marianum; Pueraria lobate; salvia miltiorrhiza
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver
• Other Study ID Numbers: K19-51000-043

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No