Phase I Trial of Silymarin for Chronic Liver Diseases (SyNCH)
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ClinicalTrials.gov Identifier: NCT00389376 |
Recruitment Status
:
Completed
First Posted
: October 18, 2006
Last Update Posted
: February 20, 2008
|
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Hepatitis C Non-Alcoholic Fatty Liver Disease | Drug: Placebo Drug: Silymarin | Phase 1 |
National Center for Complementary and Integrative Health (NCCIH) has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 56 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, 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 |
Study Start Date : | November 2006 |
Actual Primary Completion Date : | January 2008 |
Actual Study Completion Date : | February 2008 |

Arm | Intervention/treatment |
---|---|
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
|
- Adverse events [ Time Frame: 10 days ]

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Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00389376
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 |
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 |
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: |
U01AT003566-01 ( U.S. NIH Grant/Contract ) NIH grant # U01-AT0035661 |
First Posted: | October 18, 2006 Key Record Dates |
Last Update Posted: | February 20, 2008 |
Last Verified: | February 2008 |
Additional relevant MeSH terms:
Hepatitis Hepatitis C Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease Digestive System Diseases Hepatitis, Viral, Human Virus Diseases |
Flaviviridae Infections RNA Virus Infections Silymarin Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Physiological Effects of Drugs |