Vitamin D as an add-on Therapy With Pegylated Interferon and Ribavirin for Chronic Hepatitis c

Vitamin D in Addition to Pegylated Interferon and Ribavirin Compared to Pegylated Interferon and Ribavirin Alone in the Treatment of Chronic Hepatitis C Genotype 4.

Chronic hepatitis C is endemic in Egypt with a high prevalence of the resistant genotype 4. Conventional standard of care treatment has modest response with only 50% sustained virologic response. Recent reports have suggested an augmented response with the addition of vitamin D. This is a prospective randomized trial to assess the effectiveness of adding vitamin D to standard of care for chronic hepatitis C genotype 4.

Study Overview

• Status: Unknown
• Conditions: Chronic Hepatitis c
• Intervention / Treatment: Drug: pegylated interferon + ribavirin; Drug: vitamin D +pegylated interferon + ribavirin

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • National Railway Hospital Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult (male or female), 18 to 65 years of age, with chronic HCV infection
• Liver biopsy showing chronic hepatitis with significant fibrosis using Ishak scoring system
• Compensated liver disease; serum bilirubin < 1.5 mg/dl, INR no more than 1.5, serum albumin > 3.4, platelet count > 75,000 mm, and no evidence of hepatic decompensation (hepatic encephalopathy or ascites)
• Acceptable hematological and biochemical indices (hemoglobin 12.5g/dl for men and 12 g/dl for women; neutrophil count 1500/mm3 or more and serum creatinine < 1.5 mg/dl
• Patients must be serum hepatitis B surface antigen (HBsAg) negative
• Negative Antinuclear Antibodies (ANA) or titer of < 1:160
• Serum positive for anti-HCV antibodies and HCV-RNA
• Abdominal Ultrasound obtained within 3 months prior to entry in the study
• Electrocardiogram for men aged > 40 years and for women aged > 50 years
• Normal fundus examination
• Proper contraception measure throughout the course of treatment and six months later
• Female patients must not breast feed during therapy

Exclusion Criteria:

• Patients who previously received interferon
• HgbA1c > 7.5 or history of diabetes mellitus
• BMI > 34
• Women who are pregnant or breast-feeding
• Males whose female partners are either pregnant or of child-bearing potential or not using birth control and are sexually active
• Other causes of liver disease including autoimmune hepatitis
• Transplant recipients receiving immune suppression therapy
• Screening tests positive for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab or anti-HIV Ab
• Decompensated cirrhosis, history of variceal bleeding, ascites, hepatic encephalopathy, CTP score > 6 or MELD score > 8
• Absolute neutrophil count < 1500 cells/mm3; platelet count < 135,000 cells/mm3; hemoglobin < 12 g/dL for women and < 12.5 g/dL for men; or serum creatinine concentration ≥ 1.5 times ULN
• Hypothyroidism or hyperthyroidism not effectively treated with medication
• Alcohol consumption of > 40 grams per day or an alcohol use pattern that will interfere with the study
• History or other clinical evidence of significant or unstable cardiac disease
• History or other clinical evidence of chronic pulmonary disease associated with functional impairment
• Serious or severe bacterial infection(s)
• History of severe or uncontrolled psychiatric disease, including severe depression, history of suicidal ideation, suicidal attempts or psychosis requiring medication and/or hospitalization
• History of uncontrolled severe seizure disorder
• History of immunologically mediated disease requiring more than intermittent anti-inflammatory medications for management or that requires frequent or prolonged use of corticosteroids

• Patients with clinically significant retinal abnormalities

  • Subjects receiving vitamin D for any other medical condition.
  • Subjects with significant active rheumatologic or orthopaedic conditions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of care; Group A: comprises 40 treatment-naive chronic hepatitis c patients who will receive the standard of care treatment: peginterferon Alfa 2a 160 ug once weekly and weight-based ribavirin 1000 or 1200 mg/day (based on body weight < 75 kg or ≥ 75 kg, respectively) in divided doses for 48 weeks.	Drug: pegylated interferon + ribavirin; pegylated interferon 160ug once weekly Ribavirin (> 75kg:1200 mg, <75kg:1000mg daily)48 weeks
Experimental: Triple therapy; Group B: comprises 40 treatment-naive chronic HCV patients who will receive oral vitamin D 1mcg once daily plus peginterferon alfa-2a (160ug once weekly) and weight-based ribavirin 1000-1200 mg daily (based on body weight < 75 kg or ≥ 75 kg, respectively) in divided doses for 48 weeks.	Drug: vitamin D +pegylated interferon + ribavirin; Vitamin D: 1mcg once daily 48 weeks Pegylated interferon 160ug once weekly 48 weeks Ribavirin(> 75kg:1200 mg, <75kg:1000mg daily)48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained virologic response	Undetectable HCV-RNA 24 weeks after end of treatment.	72 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rapid virologic response	undetectable HCV-RNA 4 weeks after commencement of treatment	4 weeks
End-of-treatment response	undetectable HCV-RNA 48 weeks after commencement of treatment	48 weeks
Adverse events	Adverse events that could be reasonably and temporally associated with administration of drugs	72 weeks
early virologic response	Early virologic response: undetectable HCV-RNA 12 weeks after commencement of treatment. Partial early virologic response: decrease of more than 2login HCV-RNA. No early virologic response: increase, stationary or decreased less than 2log HCV-RNA.	12 weeks

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Principal Investigator: Tamer Elbaz, MD, Cairo university; Study Director: Hany Shehab, MD, Cairo university

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Anticipated): February 1, 2014
• Study Completion (Anticipated): April 1, 2014

Study Registration Dates

• First Submitted: July 31, 2012
• First Submitted That Met QC Criteria: August 1, 2012
• First Posted (Estimate): August 2, 2012

Study Record Updates

• Last Update Posted (Estimate): January 29, 2014
• Last Update Submitted That Met QC Criteria: January 28, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: vitamin d; chronic hepatitis c; hcv
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Micronutrients; Vitamins; Bone Density Conservation Agents; Interferons; Ribavirin; Vitamin D
• Other Study ID Numbers: RAIL002