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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00389376
Recruitment Status : Completed
First Posted : October 18, 2006
Last Update Posted : February 20, 2008
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by:
National Center for Complementary and Integrative Health (NCCIH)

Tracking Information
First Submitted Date  ICMJE October 16, 2006
First Posted Date  ICMJE October 18, 2006
Last Update Posted Date February 20, 2008
Study Start Date  ICMJE November 2006
Actual Primary Completion Date January 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 7, 2007)
Adverse events [ Time Frame: 10 days ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I Trial of Silymarin for Chronic Liver Diseases
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE
  • Hepatitis C
  • Non-Alcoholic Fatty Liver Disease
Intervention  ICMJE
  • Drug: Placebo
    Placebo
  • Drug: Silymarin
    140 mg every 8 hours
    Other Name: Legalon
  • Drug: Silymarin
    280 mg single dose
    Other Name: Legalon
  • Drug: Silymarin
    280 mg single dose + every 8 hours
    Other Name: Legalon
  • Drug: Silymarin
    560 mg single dose + every 8 hours
    Other Name: Legalon
  • Drug: Silymarin
    280 mg every 8 hours
    Other Name: Legalon
  • Drug: Silymarin
    700 mg single dose + every 8 hours
    Other Name: Legalon
Study Arms  ICMJE
  • Group 1
    Placebo and 140 mg single dose + every 8 hours
    Interventions:
    • Drug: Placebo
    • Drug: Silymarin
  • Group 2
    Placebo and 280 mg single dose
    Interventions:
    • Drug: Placebo
    • Drug: Silymarin
  • Group 3
    Placebo and 280mg every 8 hours
    Interventions:
    • Drug: Placebo
    • Drug: Silymarin
  • Group 4
    Placebo and 280 single dose + every 8 hours
    Interventions:
    • Drug: Placebo
    • Drug: Silymarin
  • Group 5
    Placebo and 560 mg single dose + every 8 hours
    Interventions:
    • Drug: Placebo
    • Drug: Silymarin
  • Group 6
    Placebo and 560 mg single dose + every 8 hours
    Interventions:
    • Drug: Placebo
    • Drug: Silymarin
  • Group 7
    Placebo and 700 mg single dose + every 8 hours
    Interventions:
    • Drug: Placebo
    • Drug: Silymarin
Publications * Schrieber SJ, Hawke RL, Wen Z, Smith PC, Reddy KR, Wahed AS, Belle SH, Afdhal NH, Navarro VJ, Meyers CM, Doo E, Fried MW. Differences in the disposition of silymarin between patients with nonalcoholic fatty liver disease and chronic hepatitis C. Drug Metab Dispos. 2011 Dec;39(12):2182-90. doi: 10.1124/dmd.111.040212. Epub 2011 Aug 24.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 16, 2006)
56
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 2008
Actual Primary Completion Date January 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00389376
Other Study ID Numbers  ICMJE U01AT003566-01( U.S. NIH Grant/Contract )
NIH grant # U01-AT0035661
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party SyNCH Steering Committee, NCCAM/NIDDK/UNC/UPenn/TJU/BIDMC/UPitt
Study Sponsor  ICMJE National Center for Complementary and Integrative Health (NCCIH)
Collaborators  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
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
PRS Account National Center for Complementary and Integrative Health (NCCIH)
Verification Date February 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP