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

NCT00755950 | Terminated Phase 2 DMC

• 2 other identifiers: HP-00042363LE13K0.48
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Keywords

Acute; Hepatitis; Silymarin; Global Health

Outcome Measures

Primary Outcomes (2)

• Incidence, severity and duration of Adverse Events

  Four weeks after enrollment

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

  Four weeks after enrollment

Secondary Outcomes (4)

• Normalization of ALT, AST, CRP and ESR

  Four weeks after enrollment

• Symptom resolution & return to normal physical activity

  Eight weeks after enrollment

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

  Eight weeks after enrollment

• Persistence of acute HCV with progression to chronicity

  Up to 6 months after enrollment

Study Arms (3)

1

EXPERIMENTAL

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

3

PLACEBO COMPARATOR

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

Other: Lactose monohydrate

2.

EXPERIMENTAL

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

Interventions

Silymarin DIETARY_SUPPLEMENT

280 mg three times daily for four weeks

Also known as: Legalon, Milk Thistle or St. Mary's Thistle

1

Lactose monohydrate OTHER

Lactose monohydrate 326.95 mg three times daily for four weeks

3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• MADAUS GmbH: collaborator
• The Egyptian Company for Blood Transfusion Services: collaborator
• Tanta Fever Hospital: collaborator
• Banha Fever Hospital: collaborator
• Alexandria University: collaborator

Study Sites (3)

Alexandria University Hospital

Alexandria, Alexandria Governorate, Egypt

Location

Tanta Fever Hospital

Tanta, Gharbeya Governorate, Egypt

Location

Banha Fever Hospital

Banhā, Kaluobeya Governorate, Egypt

Location

MeSH Terms

Conditions

Hepatitis

Interventions

Silymarin; milk-thistle extract

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Samer El-Kamary, MD, MPH

  University of Maryland, College Park

  PRINCIPAL INVESTIGATOR

• George T Strickland, MD, PhD,

  University of Maryland, College Park

  STUDY CHAIR

• Mohamed Hashem, MD

  University of Maryland, College Park

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 17, 2008
• First Posted: September 19, 2008
• Study Start: October 1, 2008
• Primary Completion: November 1, 2011
• Study Completion: December 1, 2015
• Last Updated: April 23, 2021

Record last verified: 2021-04

Locations

EG (3)