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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Center for Complementary and Alternative Medicine (NCCAM)
ClinicalTrials.gov Identifier:
NCT00389376
First received: October 16, 2006
Last updated: February 15, 2008
Last verified: February 2008
  Purpose

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.


Condition Intervention Phase
Hepatitis C
Non-Alcoholic Fatty Liver Disease
Drug: Placebo
Drug: Silymarin
Phase 1

National Center for Complementary and Alternative Medicine (NCCAM) has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Center for Complementary and Alternative Medicine (NCCAM):

Primary Outcome Measures:
  • Adverse events [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]

Enrollment: 56
Study Start Date: November 2006
Study Completion Date: February 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Group 1
Placebo and 140 mg single dose + every 8 hours
Drug: Placebo
Placebo
Drug: Silymarin
140 mg every 8 hours
Other Name: Legalon
Group 2
Placebo and 280 mg single dose
Drug: Placebo
Placebo
Drug: Silymarin
280 mg single dose
Other Name: Legalon
Group 3
Placebo and 280mg every 8 hours
Drug: Placebo
Placebo
Drug: Silymarin
280 mg every 8 hours
Other Name: Legalon
Group 4
Placebo and 280 single dose + every 8 hours
Drug: Placebo
Placebo
Drug: Silymarin
280 mg single dose + every 8 hours
Other Name: Legalon
Group 5
Placebo and 560 mg single dose + every 8 hours
Drug: Placebo
Placebo
Drug: Silymarin
560 mg single dose + every 8 hours
Other Name: Legalon
Group 6
Placebo and 560 mg single dose + every 8 hours
Drug: Placebo
Placebo
Drug: Silymarin
560 mg single dose + every 8 hours
Other Name: Legalon
Group 7
Placebo and 700 mg single dose + every 8 hours
Drug: Placebo
Placebo
Drug: Silymarin
700 mg single dose + every 8 hours
Other Name: Legalon

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00389376

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, North Carolina
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
University of Pittsburgh, Graduate School of Public Health
Pittsburgh, Pennsylvania, United States, 15261
Sponsors and Collaborators
Investigators
Principal Investigator: K. Rajender Reddy, MD University of Pennsylvania
Principal Investigator: Victor Navarro, MD Thomas Jefferson University
Principal Investigator: Nezam Afdhal, MD Beth Israel Deaconess Medical Center
Principal Investigator: Michael Fried, MD University of North Carolina
  More Information

No publications provided by National Center for Complementary and Alternative Medicine (NCCAM)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: SyNCH Steering Committee, NCCAM/NIDDK/UNC/UPenn/TJU/BIDMC/UPitt
ClinicalTrials.gov Identifier: NCT00389376     History of Changes
Other Study ID Numbers: U01 AT003566-01, NIH grant # U01-AT0035661
Study First Received: October 16, 2006
Last Updated: February 15, 2008
Health Authority: United States: Federal Government
United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Fatty Liver
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Silymarin
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014