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

Acute Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00755950
• Other study ID #: HP-00042363
• Secondary ID: LE13K0.48
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: October 2008
• Est. completion date: December 2015

Study information

• Verified date: April 2021
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 70
• Est. completion date: December 2015
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute CMV Hepatitis
• Acute EBV Hepatitis
• Acute Hepatitis A
• Acute Hepatitis B
• Acute Hepatitis C
• Acute Hepatitis E
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis C
• Hepatitis E

Intervention

Dietary Supplement:
• Silymarin
280 mg three times daily for four weeks
• Silymarin
420 mg three times daily for four weeks

Other:
• Lactose monohydrate
Lactose monohydrate 326.95 mg three times daily for four weeks

Locations

Country	Name	City	State
Egypt	Alexandria University Hospital	Alexandria	Alexandria Governorate
Egypt	Banha Fever Hospital	Benha	Kaluobeya Governorate
Egypt	Tanta Fever Hospital	Tanta	Gharbeya Governorate

Sponsors (6)

Lead Sponsor	Collaborator
University of Maryland, Baltimore	Alexandria University, Banha Fever Hospital, MADAUS GmbH, Tanta Fever Hospital, The Egyptian Company for Blood Transfusion Services

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence, severity and duration of Adverse Events		Four weeks after enrollment
Primary	Normalization of total (<1.0 mg/dl) and direct bilirubin (<0.3 mg/dl)		Four weeks after enrollment
Secondary	Normalization of ALT, AST, CRP and ESR		Four weeks after enrollment
Secondary	Symptom resolution & return to normal physical activity		Eight weeks after enrollment
Secondary	In AVH patients with specific etiologies resolution of clinical signs and symptoms		Eight weeks after enrollment
Secondary	Persistence of acute HCV with progression to chronicity		Up to 6 months after enrollment