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