Phase I Trial of Silymarin for Chronic Liver Diseases

NCT ID: NCT00389376

Last Updated: 2008-02-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-11-30

Study Completion Date

2008-02-29

Brief Summary

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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

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Conditions

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Hepatitis C Non-Alcoholic Fatty Liver Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Group 1

Placebo and 140 mg single dose + every 8 hours

Group Type OTHER

Placebo

Intervention Type DRUG

Placebo

Silymarin

Intervention Type DRUG

140 mg every 8 hours

Group 2

Placebo and 280 mg single dose

Group Type OTHER

Placebo

Intervention Type DRUG

Placebo

Silymarin

Intervention Type DRUG

280 mg single dose

Group 3

Placebo and 280mg every 8 hours

Group Type OTHER

Placebo

Intervention Type DRUG

Placebo

Silymarin

Intervention Type DRUG

280 mg every 8 hours

Group 4

Placebo and 280 single dose + every 8 hours

Group Type OTHER

Placebo

Intervention Type DRUG

Placebo

Silymarin

Intervention Type DRUG

280 mg single dose + every 8 hours

Group 5

Placebo and 560 mg single dose + every 8 hours

Group Type OTHER

Placebo

Intervention Type DRUG

Placebo

Silymarin

Intervention Type DRUG

560 mg single dose + every 8 hours

Group 6

Placebo and 560 mg single dose + every 8 hours

Group Type OTHER

Placebo

Intervention Type DRUG

Placebo

Silymarin

Intervention Type DRUG

560 mg single dose + every 8 hours

Group 7

Placebo and 700 mg single dose + every 8 hours

Group Type OTHER

Placebo

Intervention Type DRUG

Placebo

Silymarin

Intervention Type DRUG

700 mg single dose + every 8 hours

Interventions

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Placebo

Placebo

Intervention Type DRUG

Silymarin

140 mg every 8 hours

Intervention Type DRUG

Silymarin

280 mg single dose

Intervention Type DRUG

Silymarin

280 mg single dose + every 8 hours

Intervention Type DRUG

Silymarin

560 mg single dose + every 8 hours

Intervention Type DRUG

Silymarin

560 mg single dose + every 8 hours

Intervention Type DRUG

Silymarin

280 mg every 8 hours

Intervention Type DRUG

Silymarin

700 mg single dose + every 8 hours

Intervention Type DRUG

Other Intervention Names

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Legalon Legalon Legalon Legalon Legalon Legalon Legalon

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

NIH

Sponsor Role collaborator

National Center for Complementary and Integrative Health (NCCIH)

NIH

Sponsor Role lead

Responsible Party

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NCCAM/NIDDK/UNC/UPenn/TJU/BIDMC/UPitt

Principal Investigators

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K. Rajender Reddy, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Victor Navarro, MD

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Nezam Afdhal, MD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Michael Fried, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina

Locations

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Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh, Graduate School of Public Health

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 21865319 (View on PubMed)

Other Identifiers

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NIH grant # U01-AT0035661

Identifier Type: -

Identifier Source: secondary_id

U01AT003566-01

Identifier Type: NIH

Identifier Source: org_study_id

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