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

• ClinicalTrials.gov Identifier: NCT01083251
• Recruitment Status: Unknown
• First Posted: March 9, 2010
• Last Update Posted: January 19, 2011
• Sponsor: Ziv Hospital
• Information provided by: Ziv Hospital

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Hepatitis B Virus	Drug: Peginterferon + Vitamin D; Drug: Peginterferon; Drug: Sebivo; Drug: entecavir+ vitamin d	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Beneficial Effect of Vitamin D Supplement to Peg Interferon Alpha 2a or to Telbivudine Monotherapy in Patients With Chronic HBV Viral Infection
• Study Start Date: March 2010
• Estimated Primary Completion Date: February 2012
• Estimated Study Completion Date: December 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. treatment efficacy [ Time Frame: 120 weeks ]
   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).
2. histologic response [ Time Frame: 120 WEEKS ]
   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).

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Assy Nimer, MD; +97246828445; ASSY.N@ZIV.HEALTH.GOV.IL

Locations

Israel

Ziv medical center liver unit; Not yet recruiting

Safed, Israel, Israel, 13100

Liver clinic; Recruiting

Safed, Israel, 13100

Contact: nimer assy, MD

Sponsors and Collaborators

Ziv Hospital

More Information

• Responsible Party: Assy Nimer, Ziv medical center
• ClinicalTrials.gov Identifier: NCT01083251
• Other Study ID Numbers: 004-10
• First Posted: March 9, 2010
• Last Update Posted: January 19, 2011
• Last Verified: March 2010

Keywords provided by Ziv Hospital:

HBV; VITAMIN D; PEGITERFERON; Telbivudine

Additional relevant MeSH terms:

Hepatitis A; Hepatitis B; Hepatitis; Infections; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Blood-Borne Infections; Communicable Diseases; Hepadnaviridae Infections; DNA Virus Infections; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins; Entecavir; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Antiviral Agents; Anti-Infective Agents