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

OBJECTIVES OF STUDY Primary Objectives

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

• To compare NAS activity before and after Silymarin therapy.
• To characterize changes in ALT and AST during Silymarin therapy.
• To compare insulin resistance measured by HOMAr during Silymarin therapy.

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.