Status:
COMPLETED
Phase II Trial of Silymarin for Non-Cirrhotic Patients With Non-Alcoholic Steatohepatitis
Lead Sponsor:
Madaus Inc
Collaborating Sponsors:
University of Pennsylvania
University of North Carolina
Conditions:
Non-alcoholic Steatohepatitis
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
Silymarin, also known as milk thistle, is an alternative medicine commonly found in health food and vitamin stores. People with liver disease sometimes use silymarin because it is thought to have live...
Detailed Description
This is a multicenter, randomized, double masked, placebo controlled Phase II trial to evaluate the safety and explore the efficacy of silymarin (Legalon®) compared with placebo on hepatic histology i...
Eligibility Criteria
Inclusion
- Age at least 18 years at screening.
- Informed consent signature.
- AST (aspartate aminotransferase) or ALT (alanine aminotransferase) greater than 40 IU/L within one year of screening and at least once during the screening period.
- The participant must agree to adhere to the alcohol consumption guidelines.
- Have a liver biopsy performed within 12 months of randomization demonstrating features consistent with NASH without cirrhosis; NAS score of at least 4. Historical biopsy must include one Trichrome and one H\&E slide, otherwise the biopsy must be redone.
- No change in diabetic medications or insulin sensitizers (if applicable) between biopsy and screening or during the screening period.
- Weight loss/gain of no more than 10% between biopsy and screening, or within 30 days of screening if the biopsy is performed during the screening period.
- Negative urine pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study medication. Females of childbearing potential must be using two reliable forms of effective contraception during the study (while on study drug and during follow-up).
Exclusion
- 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 such as vitamin E, vitamin C, glutathione, alpha-tocopherol, or non-prescribed complementary alternative medications (including dietary supplements, megadose vitamins, herbal preparations, and special teas) within 30 days prior to screening. A multivitamin at standard doses will be allowed.
- Use of silymarin or other antioxidants or non-prescribed complementary alternative medications (as above) during the screening period or patient unwilling to refrain from taking these medications through completion of the study.
- BMI \> 45 kg/m2 between screening and randomization.
- Type 2 diabetes treated with oral agents other than the secretagogues or metformin; these include, thiazolidinediones, alpha-glucosidase inhibitors, exenatide, pramlintide between screening and randomization. Januvia (sitagliptin) is allowed.
- Evidence of poorly-controlled diabetes (defined as HbA1c \> 8% in patients with diabetes) between screening and randomization.
- Known allergy/sensitivity to milk thistle or its preparations.
- Use of drugs associated with a clinical or histological picture consistent with fatty liver disease or NASH for more than 12 consecutive weeks in the 1 year prior to screening; these include amiodarone, tamoxifen, methotrexate, glucocorticoids, anabolic steroids, tetracyclines, estrogens at doses greater than those used for hormone replacement, valproate/valproic acid.
- For patients using antihyperlipidemic agents or accepted anti-diabetic agents, any change of agent or dose from screening through randomization.
- Use of warfarin, metronidazole, or acetaminophen (greater than 2 grams per day) from screening through randomization.
- Lactose intolerance defined as patient reported inability to tolerate milk products.
- History of other chronic liver disease, including metabolic diseases, documented by appropriate test(s).
- Previous liver biopsy that demonstrated presence of cirrhosis.
- Radiologic imaging consistent with cirrhosis or portal hypertension.
- Clinical or histological evidence of cirrhosis or, in the opinion of the investigator, the inability to safely obtain a liver biopsy due to technical reasons, such as body habitus.
- Evidence of decompensated liver disease defined as any of the following: serum albumin \<3.2 g/dl, total bilirubin \> 1.5 mg/dl, or PT/INR (Prothrombin Time/International Normalized Ratio) \> 1.3 times normal at screening, or history or presence of ascites or encephalopathy, or bleeding from esophageal varices.
- Platelet count \< 130,000/mm3 at screening.
- Serum creatinine of 2.0 mg/dL or greater or CrCl ≤ 60cc/min, or on dialysis, at screening. The creatinine clearance (CrCl) will be calculated according to Cockcroft-Gault.
- Average alcohol consumption of more than one drink or equivalent (\>12 grams) per day or more than two (2) drinks on any one day over the 30 days prior to screening. Patients who met either criterion more than 30 days prior to screening must have consumed a monthly average of 12 grams or less per day of alcohol for at least six months prior to screening.
- Evidence of drug abuse in the year prior to screening or prior to randomization.
- History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, severe psoriasis, rheumatoid arthritis) that could affect the assessment of biomarkers of inflammation.
- History of solid organ or bone marrow transplantation.
- History of thyroid disease poorly controlled on prescribed medications.
- Use of oral steroids for more than 14 days within 30 days of screening or prior to randomization.
- Primary hepatic malignancy.
- Secondary hepatic malignancy (metastatic disease) or extrahepatic malignancy.
- Women with ongoing pregnancy or breast feeding, or contemplating pregnancy.
- History of bariatric surgery, or undergoing evaluation for bariatric surgery.
- Participation in a research drug trial, exclusive of the SyNCH Phase I trial, within 30 days of screening.
- History or other evidence of severe illness or any other conditions that would make the patient, in the opinion of the investigator, unsuitable for the study (such as poorly controlled psychiatric disease, coronary artery disease, or active gastrointestinal conditions that might interfere with drug absorption).
- Inability or unwillingness to give informed consent or abide by the study protocol.
Key Trial Info
Start Date :
April 1 2008
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
November 1 2012
Estimated Enrollment :
78 Patients enrolled
Trial Details
Trial ID
NCT00680407
Start Date
April 1 2008
End Date
November 1 2012
Last Update
July 17 2019
Active Locations (6)
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1
Beth Isreal Deaconess Medical Center
Boston, Massachusetts, United States, 02215
2
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599
3
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
4
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107