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

Primary Purpose

Acute Hepatitis A, Acute Hepatitis B, Acute Hepatitis C

Status

Terminated

Phase

Phase 2

Locations

Egypt

Study Type

Interventional

Intervention

Silymarin

Lactose monohydrate

About this trial

This is an interventional supportive care trial for Acute Hepatitis A focused on measuring Acute, Hepatitis, Silymarin, Global Health

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Alexandria University Hospital
Tanta Fever Hospital
Banha Fever Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Arm Description

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)

Placebo: Lactose monohydrate; Vitamin B complex: B1:thiamine (1.3mg), B2:riboflavin (1.0mg) and B3: nicotinamide (16.5mg)

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)

Outcomes

Primary Outcome Measures

Incidence, severity and duration of Adverse Events

Normalization of total (<1.0 mg/dl) and direct bilirubin (<0.3 mg/dl)

Secondary Outcome Measures

Normalization of ALT, AST, CRP and ESR

Symptom resolution & return to normal physical activity

In AVH patients with specific etiologies resolution of clinical signs and symptoms

Persistence of acute HCV with progression to chronicity

Full Information

NCT ID

NCT00755950

First Posted

September 17, 2008

Last Updated

April 21, 2021

Sponsor

University of Maryland, Baltimore

Collaborators

MADAUS GmbH, The Egyptian Company for Blood Transfusion Services, Tanta Fever Hospital, Banha Fever Hospital, Alexandria University

1. Study Identification

Unique Protocol Identification Number

NCT00755950

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Terminated

Why Stopped

Low enrollment

Study Start Date

October 2008 (undefined)

Primary Completion Date

November 2011 (Actual)

Study Completion Date

December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Maryland, Baltimore

Collaborators

MADAUS GmbH, The Egyptian Company for Blood Transfusion Services, Tanta Fever Hospital, Banha Fever Hospital, Alexandria University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Acute, Hepatitis, Silymarin, Global Health

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

70 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

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)

Arm Title

Arm Type

Placebo Comparator

Arm Description

Placebo: Lactose monohydrate; Vitamin B complex: B1:thiamine (1.3mg), B2:riboflavin (1.0mg) and B3: nicotinamide (16.5mg)

Arm Title

Arm Type

Experimental

Arm Description

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)

Intervention Type

Dietary Supplement

Intervention Name(s)

Silymarin

Other Intervention Name(s)

Legalon, Milk Thistle or St. Mary's Thistle

Intervention Description

280 mg three times daily for four weeks

Intervention Type

Dietary Supplement

Intervention Name(s)

Silymarin

Other Intervention Name(s)

Legalon, Milk Thistle or St. Mary's Thistle

Intervention Description

420 mg three times daily for four weeks

Intervention Type

Other

Intervention Name(s)

Lactose monohydrate

Intervention Description

Lactose monohydrate 326.95 mg three times daily for four weeks

Primary Outcome Measure Information:

Title

Incidence, severity and duration of Adverse Events

Time Frame

Four weeks after enrollment

Title

Normalization of total (<1.0 mg/dl) and direct bilirubin (<0.3 mg/dl)

Time Frame

Four weeks after enrollment

Secondary Outcome Measure Information:

Title

Normalization of ALT, AST, CRP and ESR

Time Frame

Four weeks after enrollment

Title

Symptom resolution & return to normal physical activity

Time Frame

Eight weeks after enrollment

Title

In AVH patients with specific etiologies resolution of clinical signs and symptoms

Time Frame

Eight weeks after enrollment

Title

Persistence of acute HCV with progression to chronicity

Time Frame

Up to 6 months after enrollment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Samer El-Kamary, MD, MPH

Organizational Affiliation

University of Maryland, College Park

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

George T Strickland, MD, PhD,

Organizational Affiliation

University of Maryland, College Park

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Mohamed Hashem, MD

Organizational Affiliation

University of Maryland, College Park

Official's Role

Study Director

Facility Information:

Facility Name

Alexandria University Hospital

City

Alexandria

State/Province

Alexandria Governorate

Country

Egypt

Facility Name

Tanta Fever Hospital

City

Tanta

State/Province

Gharbeya Governorate

Country

Egypt

Facility Name

Banha Fever Hospital

City

Benha

State/Province

Kaluobeya Governorate

Country

Egypt

12. IPD Sharing Statement

Learn more about this trial

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

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