Randomized Placebo-controlled Trial Evaluating the Safety and Efficacy of Silymarin Treatment in Patients With Acute Viral Hepatitis - Full Text View

Sponsor:	University of Maryland
Collaborators:	MADAUS GmbH The Egyptian Company for Blood Transfusion Services (EgyBlood) Tanta Fever Hospital Banha Fever Hospital Alexandria University
Information provided by (Responsible Party):	Samer S. El-Kamary, University of Maryland
ClinicalTrials.gov Identifier:	NCT00755950

Purpose

The purpose of this study is to assess whether two higher doses (280mg or 420mg three times daily)of silymarin therapy are safe and tolerable, and shorten the illness in patients with acute viral hepatitis compared to placebo.

Condition	Intervention	Phase
Acute Hepatitis A Acute Hepatitis B Acute Hepatitis C Acute Hepatitis E Acute EBV Hepatitis Acute CMV Hepatitis	Dietary Supplement: Silymarin Other: Lactose monohydrate	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Supportive Care
Official Title:	A Multicentre, Double-blind, Randomized, Placebo-controlled, Phase II/III Study to Evaluate the Safety and Efficacy of 280 mg and 420 mg Silymarin TID (Legalon® Capsules) Administered for Four Weeks in Subjects With Acute Viral Hepatitis With a Four Week Follow-up Period

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B Hepatitis C

Drug Information available for: Lactose Silymarin Hepatitis A Vaccines

U.S. FDA Resources

Further study details as provided by University of Maryland:

Primary Outcome Measures:

Incidence, severity and duration of Adverse Events [ Time Frame: Four weeks after enrollment ] [ Designated as safety issue: Yes ]
Normalization of total (<1.0 mg/dl) and direct bilirubin (<0.3 mg/dl) [ Time Frame: Four weeks after enrollment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Normalization of ALT, AST, CRP and ESR [ Time Frame: Four weeks after enrollment ] [ Designated as safety issue: No ]
Symptom resolution & return to normal physical activity [ Time Frame: Eight weeks after enrollment ] [ Designated as safety issue: No ]
In AVH patients with specific etiologies resolution of clinical signs and symptoms [ Time Frame: Eight weeks after enrollment ] [ Designated as safety issue: No ]
Persistence of acute HCV with progression to chronicity [ Time Frame: Up to 6 months after enrollment ] [ Designated as safety issue: No ]

Estimated Enrollment:	213
Study Start Date:	October 2008
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 280 mg of Silymarin administered three times daily for 4 weeks; Vitamin B complex: B1:thiamine (1.3mg), B2:riboflavin (1.0mg) and B3: nicotinamide (16.5mg)	Dietary Supplement: Silymarin 280 mg three times daily for four weeks Other Name: Legalon, Milk Thistle or St. Mary's Thistle
Placebo Comparator: 3 Placebo: Lactose monohydrate; Vitamin B complex: B1:thiamine (1.3mg), B2:riboflavin (1.0mg) and B3: nicotinamide (16.5mg)	Other: Lactose monohydrate Lactose monohydrate 326.95 mg three times daily for four weeks
Experimental: 2. 420 mg silymarin three times daily for four weeks; Vitamin B complex: B1:thiamine (1.3mg), B2:riboflavin (1.0mg) and B3: nicotinamide (16.5mg)	Dietary Supplement: Silymarin 420 mg three times daily for four weeks Other Name: Legalon, Milk Thistle or St. Mary's Thistle

Detailed Description:

Currently, acute viral hepatitis (AVH) management is based on diet and rest and silymarin remains among the most popular herbs being used for treating viral hepatitis both in the U.S. and abroad. Although numerous randomized clinical trials have been conducted to assess the efficacy of silymarin on chronic hepatitis C, very few studies were done to assess the efficacy of silymarin in acute viral hepatitis. Among those, efficacy of silymarin has not been established. This could be attributed to the small number of studies conducted, small sample sizes, high drop out rates, and low doses of silymarin used. Therefore, it is justified to evaluate silymarin safety and efficacy using higher doses than previously studied in AVH.

Primary safety objective:

To assess safety and tolerability of two silymarin doses in patients with AVH as determined by the number and percentage of subjects who develop Adverse Events in each group elicited by a questionnaire administered at specific visits and by hematology, blood chemistry and physical examinations.

Primary efficacy objective:

To assess the percentage of subjects who normalize their total and direct bilirubin in each group.

Secondary Objective:

To assess the percentage of subjects in each group who:

Normalize their liver enzymes, i.e. alanine aminotransferase (ALT), aspartate aminotransferase (AST) and inflammatory reactants, i.e. erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).
Resolve their clinical symptoms of AVH and return to baseline activity levels and quality of life (QOL) assessed by physical examinations and using a previously evaluated Arabic-translated SF-36 form adapted for use with patients with liver diseases.

To assess:

Differences in silymarin response in different AVH etiologies (i.e. HAV, HBV, HCV, HEV) using subgroup analyses.

To compare:

Progression of acute to chronic HCV infection in subjects with HCV-caused acute AVH.

Eligibility

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

Criteria

Inclusion Criteria:

Diagnosis of acute viral hepatitis (<1 month) as manifested by a combination of the following symptoms: jaundice, dark-colored urine, light-colored stools, pruritus, pruritic red hives, fever, nausea, vomiting, anorexia, aversion to smoking and right upper abdominal discomfort, pain or feeling of pressure.
Serum ALT level > 2.5 times the upper limit of normal.
Albumin level >3.5 gm/dl
Negative anti-HCV antibody
Males and females >= 18 years of age.
Subject has given written informed consent. If patient is between 18 and 21 years parents/legal guardian have/has also signed the informed consent form.
The subject is able and willing to undertake all study-required procedures and has the ability to take oral medications.

Exclusion Criteria:

Subjects < 18 years of age
Pregnant or breastfeeding women
Suspected hypersensitivity to silymarin or multivitamins
Advanced liver disease (e.g. ascites, bleeding esophageal varices and hepatic encephalopathy)
Chronic liver disease as cirrhosis
Subjects with positive anti-HCV antibody
Simultaneous elevation of bilirubin > 10 mg/dl along with an ALT level between 100 and 150 U/L
Platelets count <150,000
Subjects with morbid obesity i.e. a Body Mass Index (BMI) > 40
Subjects with severe illness, e.g., multisystem failure, cancer or poorly controlled diabetes i.e. known diabetic with Hemoglobin A1C (HbA1C)>7%
Obvious history of drug-induced acute hepatitis. A careful history of all medications, pesticide and other hepatotoxic exposures occurring within one month prior to symptom onset will be taken. If a patient is unaware of the name of the drugs, (s)he will be asked to bring it for inspection.
Current use of Silymarin or recent use within past two weeks.
Other conditions, which in the opinion of the investigators, makes the patient unsuitable for enrollment or could interfere with his/her participation in, and completion of, the protocol (e.g. severe mental illness)
The subject is currently participating in any clinical trial (marketed product or otherwise), or has done so within 30 days or 5 half-lives (whichever is longer) prior to screening visit
History or current drug or alcohol abuse
Female patient with childbearing potential without negative pregnancy test
Patient is known to be HIV positive.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00755950

Contacts

Contact: Samer El-Kamary, MD, MPH		selkamar@epi.umaryland.edu
Contact: Mohamed Hashem, MD		mhashem@epi.umaryland.edu

Locations

Egypt
Alexandria University Hospital	Recruiting
Alexandria, Alexandria Governorate, Egypt
Tanta Fever Hospital	Recruiting
Tanta, Gharbeya Governorate, Egypt
Banha Fever Hospital	Recruiting
Benha, Kaluobeya Governorate, Egypt

Sponsors and Collaborators

University of Maryland

MADAUS GmbH

The Egyptian Company for Blood Transfusion Services (EgyBlood)

Tanta Fever Hospital

Banha Fever Hospital

Alexandria University

Investigators

Principal Investigator:	Samer El-Kamary, MD, MPH	University of Maryland
Study Chair:	George T Strickland, MD, PhD,	University of Maryland
Study Director:	Mohamed Hashem, MD	University of Maryland

More Information

No publications provided

Responsible Party:	Samer S. El-Kamary, Assistant Professor, University of Maryland
ClinicalTrials.gov Identifier:	NCT00755950 History of Changes
Other Study ID Numbers:	HP-00042363, LE13K0.48
Study First Received:	September 17, 2008
Last Updated:	August 19, 2011
Health Authority:	United States: Institutional Review Board; Egypt: Institutional Review Board; Egypt: Ministry of Health and Population

Keywords provided by University of Maryland:

Acute
Hepatitis
Silymarin
Global Health

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis E
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections

RNA Virus Infections
Hepadnaviridae Infections
DNA 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 February 09, 2012