Silymarin for the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD)

Non-alcoholic Fatty Liver Disease Clinical Trial

Official title:

A Randomised, Double-blind, Placebo-controlled, Phase II, Single-centre Study to Assess the Safety and Efficacy of Silymarin 700 mg Capsules TID for the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02006498
• Other study ID #: LE13T0.01
• Status: Completed
• Phase: Phase 2
• First received: December 4, 2013
• Last updated: January 6, 2016
• Start date: June 2012
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: University of Malaya
• Contact: n/a
• Is FDA regulated: No
• Health authority: Malaysia: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This is a randomised study to examine whether high dose Sillymarin will be able to help improve fat-induced liver damage in the liver. The study hypothesis is that high dose Sillymarin will be able to reduce steato-hepatitis (fat-related liver inflammation) better than placebo.

Description:

OBJECTIVES OF STUDY Primary Objectives

1. To assess the safety and adverse event profile of Silymarin compared to placebo.

2. To assess the efficacy of Silymarin as defined by an improvement in non-alcoholic steatosis (NAS) activity score by at least 30% from baseline compared to placebo.

Secondary Objectives

1. To compare NAS activity before and after Silymarin therapy.

2. To characterize changes in ALT and AST during Silymarin therapy.

3. To compare insulin resistance measured by HOMAr during Silymarin therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female 18 years of age or older.

• Diagnosed with NASH (refer to Section 5.2)

• AST and/or ALT greater than 40 IU/L.

• Must agree to adhere to alcohol consumption guideline.

• Weight gain//loss of no more than 10% between biopsy and screening or within 30 days of screening if the biopsy is performed during the screening period.

• No change in diabetic and/or lipid medications between biopsy and screening or within 30 days of screening if the biopsy is performed during the screening period

Exclusion Criteria:

• Use of silymarin or other milk thistle preparations for a period of 90 consecutive days or longer between biopsy and initial screening, or within 30 days prior to screening if the biopsy is performed during the screening period.

• Use of other antioxidants or non-prescribed complementary alternative medications for a period of 90 consecutive days or longer between biopsy and initial screening, or within 30 days prior to screening if the biopsy is performed during the screening period.

• Use of warfarin, metronidazole, or acetaminophen (greater than 2 grams per day) between screening and randomization.

• Use of oral steroids for more than 14 days of screening or prior to randomization.

• BMI = 35 kg/m2 between screening and randomization.

• Poorly-controlled diabetes (HbA1c > 8 %) between screening and randomization

• Diabetes mellitus treated with oral agents other than the secretagogues or metformin between screening and randomization. Sitagliptin is allowed.

• For patients using anti-hyperlipidemic agents or accepted anti-diabetic agents, any change of agent or dose between screening and randomization.

• Radiologic imaging consistent with cirrhosis or portal hypertension.

• Evidence of decompensated liver disease

• Platelet count < 130 x 109 /L at screening.

• History of bariatric surgery, or undergoing evaluation for bariatric surgery.

• Known allergy/sensitivity to milk thistle or its preparations.

• History of immunologically mediated disease

• History of thyroid disease poorly controlled on prescribed medications.

• History of solid organ or bone marrow transplantation.

• Primary hepatic malignancy.

• Secondary hepatic malignancy or extrahepatic malignancy.

• Serum Creatinine of 176 µmol/L or greater or creatinine clearance (calculated according to Cockcroft-Gault) 60 mL/min or less, or on dialysis, at screening.

• Severe illness or any other conditions that would make the patient, in the opinion of the investigator, unsuitable for the study.

• Women with ongoing pregnancy or breast feeding, or contemplating pregnancy.

• Women of childbearing potential who are not practicing an acceptable form of birth control.

• Participation in a research drug trial within 30 days of screening.

• Inability or unwillingness to give informed consent or abide by the study protocol.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease

Intervention

Drug:
• Sillymarin
Sillymarin is derived from the milk thistle plant, Silybum marianum, a herbal remedy that has been used for centuries for diseases of the liver. It is a complex mixture of 6 major flavonolignans (silybins A and B, isosilybins A and B, silychristin, and silydianin), as well as other minor polyphenolic compounds.
• Placebo
Placebo capsule with same appearances as study drug

Locations

Country	Name	City	State
Malaysia	University Malaya Medical Centre	Kuala Lumpur	Federal Territory

Sponsors (2)

Lead Sponsor	Collaborator
University of Malaya	Rottapharm

Country where clinical trial is conducted

Malaysia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To characterize changes in ALT and AST during Silymarin therapy		12 months	No
Other	To compare insulin resistance measured by HOMAr during Silymarin therapy.		12 months	No
Primary	To assess the efficacy of Silymarin as defined by an improvement in non-alcoholic steatosis (NAS) activity score by at least 30% from baseline compared to placebo		12 months	No
Secondary	To assess the safety and adverse event profile of Silymarin compared to placebo		12 months	Yes