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

Tracking Information

• First Submitted Date: March 3, 2010
• First Posted Date: March 9, 2010
• Last Update Posted Date: January 19, 2011
• Study Start Date: March 2010
• Estimated Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 8, 2010)

• 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).
• 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).

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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

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

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatitis B Virus

Intervention

• Drug: Peginterferon + Vitamin D
  180 mcg/week + 400 IUX2/day
• Drug: Peginterferon
  180 mcg/week
• Drug: Sebivo
  Telbivudine 600 mg daily
• Drug: entecavir+ vitamin d
  entecavir 1 mg daily+ vitamin d

Study Arms

• 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
  Intervention: Drug: Peginterferon + Vitamin D
• Active Comparator: Peginterferon
  Intervention: Drug: Peginterferon
• Active Comparator: Sebivo
  Nucleotide Analog Telbivudine 600 mg daily
  Intervention: Drug: Sebivo
• Active Comparator: entecavir + vitamin d
  baraclude 1 mg x1/ day + vitamin d
  Intervention: Drug: entecavir+ vitamin d

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: March 8, 2010): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2012
• Estimated Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel

Administrative Information

• NCT Number: NCT01083251
• Other Study ID Numbers: 004-10
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Assy Nimer, Ziv medical center
• Study Sponsor: Ziv Hospital
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Ziv Hospital
• Verification Date: March 2010