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

NCT02006498 | Completed Phase 2

• 1 other identifier: LE13T0.01
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non-alcoholic Fatty Liver Disease

Keywords

non-alcoholic fatty liver disease; sillymarin; randomised trial; non-alcoholic steatohepatitis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

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

  12 months

Other Outcomes (2)

• To characterize changes in ALT and AST during Silymarin therapy

  12 months

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

  12 months

Study Arms (2)

Sillymarin

EXPERIMENTAL

Active component study medication

Drug: Sillymarin

Placebo

PLACEBO COMPARATOR

Placebo capsules

Drug: Placebo

Interventions

Sillymarin DRUG

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.

Also known as: Legalon

Sillymarin

Placebo DRUG

Placebo capsule with same appearances as study drug

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Malaya: lead
• Rottapharm: collaborator

Study Sites (1)

University Malaya Medical Centre

Kuala Lumpur, Kuala Lumpur, 59100, Malaysia

Location

Related Publications (1)

• Wah Kheong C, Nik Mustapha NR, Mahadeva S. A Randomized Trial of Silymarin for the Treatment of Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol. 2017 Dec;15(12):1940-1949.e8. doi: 10.1016/j.cgh.2017.04.016. Epub 2017 Apr 15.

  PMID: 28419855 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Silymarin

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Sanjiv Mahadeva, MD, MRCP

  University of Malaya

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2013
• First Posted: December 10, 2013
• Study Start: June 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 8, 2016

Record last verified: 2016-01

Locations

MY (1)