Phase I Trial of Silymarin for Chronic Liver Diseases (SyNCH)

February 15, 2008 updated by: National Center for Complementary and Integrative Health (NCCIH)

Single and Multiple Dose Escalation Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Administered Silymarin (Legalon) in Non-Cirrhotic Subjects With Chronic Hepatitis C or Non-Alcoholic Fatty Liver Disease

The purpose of this study is to determine the safety and tolerability of different dosages of silymarin on subjects with Hepatitis C or Non-Alcoholic Fatty Liver Disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • The University of North Carolina at Chapel Hill
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
      • Pittsburgh, Pennsylvania, United States, 15261
        • University of Pittsburgh, Graduate School of Public Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria

Subjects will be eligible for enrollment in this study if they meet the following criteria:

  • Males or females; age at least 18 years at screening
  • Abnormal ALT > 65 IU/L (ie, approximately 1.5 x upper limit of normal)
  • Negative urine pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of silymarin. Females of childbearing potential must be using two reliable forms of effective contraception during the study (while on drug and during follow-up)
  • Hepatitis C virus (HCV) patients
  • Previous treatment with any interferon-based therapy without sustained virological response.
  • Serum HCV RNA above quantifiable level of detection by the assay, within 1 year of screening and after the end of therapy
  • No antiviral therapy for at least 6 months prior to screening visit
  • Nonalcoholic fatty liver disease (NAFLD) patients:
  • Liver biopsy compatible with NAFLD within 3 years of screening
  • Absence of other liver diseases by serological screening (anti-HCV, HBsAg), historical serological data from within 3 years of screening is acceptable.
  • Before entering the study, subjects must agree not to consume alcohol for 48 hours prior to PK sampling days or while on study.

Exclusion criteria

Subjects with any of the following will not be eligible for participation:

  • Use of silymarin or other milk thistle preparations within 30 days of screening
  • Use of other antioxidants such as vitamin E, vitamin C, glutathione, alpha-tocopherol, within 30 days of screening. A multivitamin at standard doses will be allowed.
  • Allergy/sensitivity to milk thistle or its preparations
  • Use of silymarin or other antioxidants (as above) during the screening period.
  • Use of warfarin, metronidazole or chronic use of acetaminophen greater than two gram per day
  • Previous liver biopsy that demonstrated presence of cirrhosis
  • Previous liver biopsy that demonstrated greater than or equal to 15% steatosis or evidence of steatohepatitis for HCV cohort
  • Positive test for anti-HIV or HBsAg within 3 years of screening
  • Positive urine drug screen for drugs of abuse at screening
  • Alcohol consumption of more than one drink or equivalent (>12 grams) per day. Patients who consumed more than this in the past must have maintained a level 12 grams or less per day of alcohol consumption for at least six months prior to screening.
  • History of other chronic liver disease, including metabolic diseases, documented by appropriate test(s)
  • Women with ongoing pregnancy or breast-feeding, or contemplating pregnancy
  • Platelet count <130,000 cells/mm3.
  • Serum creatinine level >1.5 times the upper limit of normal at screening, or CrCl 60 cc/min, or currently on dialysis. The creatinine clearance (CrCl) will be calculated according to Cockcroft-Gault.
  • Evidence of alcohol or drug abuse within 6 months prior to screening
  • 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 > 1.3 times normal at screening, or history or presence of ascites or encephalopathy, or bleeding from esophageal varices
  • 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)
  • History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hepatitis, autoimmune hemolytic anemia, severe psoriasis, rheumatoid arthritis) that could affect inflammatory biomarkers
  • History of solid organ or bone marrow transplantation
  • History of thyroid disease poorly controlled on prescribed medications
  • Use of oral steroids within 30 days prior to screening
  • Concurrent medications that are CYP3A4 inducers
  • Inability or unwillingness to provide informed consent or abide by the study protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Group 1
Placebo and 140 mg single dose + every 8 hours
Drug: Placebo
Placebo
Drug: Silymarin
140 mg every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
280 mg single dose
Other Names:
  • Legalon
Drug: Silymarin
280 mg single dose + every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
560 mg single dose + every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
280 mg every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
700 mg single dose + every 8 hours
Other Names:
  • Legalon
Other: Group 2
Placebo and 280 mg single dose
Drug: Placebo
Placebo
Drug: Silymarin
140 mg every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
280 mg single dose
Other Names:
  • Legalon
Drug: Silymarin
280 mg single dose + every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
560 mg single dose + every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
280 mg every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
700 mg single dose + every 8 hours
Other Names:
  • Legalon
Other: Group 3
Placebo and 280mg every 8 hours
Drug: Placebo
Placebo
Drug: Silymarin
140 mg every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
280 mg single dose
Other Names:
  • Legalon
Drug: Silymarin
280 mg single dose + every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
560 mg single dose + every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
280 mg every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
700 mg single dose + every 8 hours
Other Names:
  • Legalon
Other: Group 4
Placebo and 280 single dose + every 8 hours
Drug: Placebo
Placebo
Drug: Silymarin
140 mg every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
280 mg single dose
Other Names:
  • Legalon
Drug: Silymarin
280 mg single dose + every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
560 mg single dose + every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
280 mg every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
700 mg single dose + every 8 hours
Other Names:
  • Legalon
Other: Group 5
Placebo and 560 mg single dose + every 8 hours
Drug: Placebo
Placebo
Drug: Silymarin
140 mg every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
280 mg single dose
Other Names:
  • Legalon
Drug: Silymarin
280 mg single dose + every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
560 mg single dose + every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
280 mg every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
700 mg single dose + every 8 hours
Other Names:
  • Legalon
Other: Group 6
Placebo and 560 mg single dose + every 8 hours
Drug: Placebo
Placebo
Drug: Silymarin
140 mg every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
280 mg single dose
Other Names:
  • Legalon
Drug: Silymarin
280 mg single dose + every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
560 mg single dose + every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
280 mg every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
700 mg single dose + every 8 hours
Other Names:
  • Legalon
Other: Group 7
Placebo and 700 mg single dose + every 8 hours
Drug: Placebo
Placebo
Drug: Silymarin
140 mg every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
280 mg single dose
Other Names:
  • Legalon
Drug: Silymarin
280 mg single dose + every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
560 mg single dose + every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
280 mg every 8 hours
Other Names:
  • Legalon
Drug: Silymarin
700 mg single dose + every 8 hours
Other Names:
  • Legalon

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Adverse events
Time Frame: 10 days
10 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Center for Complementary and Integrative Health (NCCIH)

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

  • Principal Investigator: Michael Fried, MD, University of North Carolina

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2006

Primary Completion (Actual)

January 1, 2008

Study Completion (Actual)

February 1, 2008

Study Registration Dates

First Submitted

October 16, 2006

First Submitted That Met QC Criteria

October 16, 2006

First Posted (Estimate)

October 18, 2006

Study Record Updates

Last Update Posted (Estimate)

February 20, 2008

Last Update Submitted That Met QC Criteria

February 15, 2008

Last Verified

February 1, 2008

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • U01AT003566-01 (U.S. NIH Grant/Contract)
  • NIH grant # U01-AT0035661

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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