NCT00389376

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
56

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Nov 2006

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 16, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 18, 2006

Completed
14 days until next milestone

Study Start

First participant enrolled

November 1, 2006

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2008

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2008

Completed
Last Updated

February 20, 2008

Status Verified

February 1, 2008

Enrollment Period

1.2 years

First QC Date

October 16, 2006

Last Update Submit

February 15, 2008

Conditions

Hepatitis CNon-Alcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (1)

  • Adverse events

    10 days

Study Arms (7)

Group 1

OTHER

Placebo and 140 mg single dose + every 8 hours

Drug: PlaceboDrug: Silymarin

Group 2

OTHER

Placebo and 280 mg single dose

Drug: PlaceboDrug: Silymarin

Group 3

OTHER

Placebo and 280mg every 8 hours

Drug: PlaceboDrug: Silymarin

Group 4

OTHER

Placebo and 280 single dose + every 8 hours

Drug: PlaceboDrug: Silymarin

Group 5

OTHER

Placebo and 560 mg single dose + every 8 hours

Drug: PlaceboDrug: Silymarin

Group 6

OTHER

Placebo and 560 mg single dose + every 8 hours

Drug: PlaceboDrug: Silymarin

Group 7

OTHER

Placebo and 700 mg single dose + every 8 hours

Drug: PlaceboDrug: Silymarin

Interventions

PlaceboDRUG

Placebo

Group 1Group 2Group 3Group 4Group 5Group 6Group 7
SilymarinDRUG

140 mg every 8 hours

Also known as: Legalon
Group 1

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh, Graduate School of Public Health

Pittsburgh, Pennsylvania, 15261, United States

Location

Related Publications (1)

  • 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.

    PMID: 21865319DERIVED

MeSH Terms

Conditions

Hepatitis CNon-alcoholic Fatty Liver Disease

Interventions

Silymarin

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitisLiver DiseasesDigestive System DiseasesFatty Liver

Intervention Hierarchy (Ancestors)

FlavonolignansFlavonoidsChromonesBenzopyransPyransHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • 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

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
NIH
Expanded Access
Yes

Study Record Dates

First Submitted

October 16, 2006

First Posted

October 18, 2006

Study Start

November 1, 2006

Primary Completion

January 1, 2008

Study Completion

February 1, 2008

Last Updated

February 20, 2008

Record last verified: 2008-02

Locations

US(5)