The Beneficial Effect of Vitamin D Supplement to Peg Interferon Alpha 2a or to Telbivudine Monotherapy in Patients With Chronic Hepatitis B Virus (HBV) Infection

The Beneficial Effect of Vitamin D Supplement to Peg Interferon Alpha 2a or to Telbivudine Monotherapy in Patients With Chronic HBV Viral Infection

Abstract

Telbivudine is a potent inhibitor of HBV but, due to a low genetic barrier to resistance, a high incidence of resistance has been observed in patients with high baseline levels of replication and in those with detectable HBV DNA after 24 weeks of therapy (A1). Telbivudine might be used in patients with good predictors of response (HBV DNA <2 X 106 IU/ ml, i.e. approximately 107 copies/ ml, or 6.3 log 10 IU/ ml at baseline) with verification of HBV DNA suppression below detection in real time PCR assay at 24 weeks.(EASL Guidelines for HBV 2009) The therapy of Pegylated-interferon-alpha-2a is considered as the standard of care for patients with chronic hepatitis b viral infection. However, recent study by Buster et al showed that a sustained viral response (SVR less than 2000 iu.ml at 6 months after treatment)) is obtained in 8 % of patients with genotype D, 30% genotype A, and 20-25% genotypes B or C (47). Vitamin D is a potent immune-modulator; and has been shown to improve SVR in combination with peg interferone in patients with chronic HCV viral infection (48). The impact of vitamin D on virologic response rates of interferon-based treatment of CHB is unknown. The aim of this study therefore was to assess whether Vitamin D, added to the conventional peg therapy in CHB, or to nucleotide analogues could improve the treatment efficacy

Study Overview

• Status: Unknown
• Conditions: Hepatitis B Virus
• Intervention / Treatment: Drug: Peginterferon + Vitamin D; Drug: Peginterferon; Drug: Sebivo; Drug: entecavir+ vitamin d

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Safed, Israel, 13100
    • Recruiting
    • Liver Clinic
    • Contact: nimer assy, MD
  • Safed, Israel, Israel, 13100
    • Not yet recruiting
    • Ziv medical center liver unit

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• patients were eligible if they had been HBsAg positive for at least 6 months,
• patients were HBeAg positive or negative,
• patients had increased serum ALT levels between 1 and 10 times the upper limit of normal (ULN),
• patients had serum HBV-DNA levels greater than 1.0 x 10E5 copies/mL (2.0 X 10E4 IUmL), and
• patients had findings on a liver biopsy within the preceding 12 months that were consistent with the presence of chronic hepatitis B.

Exclusion Criteria:

• decompensated liver disease,
• antiviral therapy within 6 months before randomization,
• viral co-infections (hepatitis C virus, hepatitis delta virus, or human immunodeficiency virus), or
• pre-existent neutropenia or thrombocytopenia.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Peg + Vitamin D; Treatment arm with vitamin D will be treated first with vitamin D supplement for 3 months before the initiation of antiviral therapy. Vitamin D levels will be measures at baseline and three months after. The serum vitamin D-25-OH levels should be > 32 ng/ml before the initiation of antiviral treatment). HBV DNA levels will be also measure at baseline and after 3 months of mono therapy with vitamin D	Drug: Peginterferon + Vitamin D; 180 mcg/week + 400 IUX2/day
Active Comparator: Peginterferon	Drug: Peginterferon; 180 mcg/week
Active Comparator: Sebivo; Nucleotide Analog Telbivudine 600 mg daily	Drug: Sebivo; Telbivudine 600 mg daily
Active Comparator: entecavir + vitamin d; baraclude 1 mg x1/ day + vitamin d	Drug: entecavir+ vitamin d; entecavir 1 mg daily+ vitamin d

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
treatment efficacy	The primary end point will be sustained viral response which was defined as clearance of HBeAg from serum and HBV DNA less than 10,000 copies/mL (2000 IU/mL) at 6 months after treatment. HBsAg titre during treatment and at 6 months follow up will be measured also (ROCH or Abott Kit).	120 weeks
histologic response	Another primary endpoint will be histologic response (reduction of at least two points without fibrosis worsening in the total score on the Histological Activity Index).	120 WEEKS

Collaborators and Investigators

• Sponsor: Ziv Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Anticipated): February 1, 2012
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: March 3, 2010
• First Submitted That Met QC Criteria: March 8, 2010
• First Posted (Estimate): March 9, 2010

Study Record Updates

• Last Update Posted (Estimate): January 19, 2011
• Last Update Submitted That Met QC Criteria: January 17, 2011
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: HBV; Telbivudine; VITAMIN D; PEGITERFERON
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Entecavir; Vitamins; Ergocalciferols
• Other Study ID Numbers: 004-10