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

• ClinicalTrials.gov Identifier: NCT01655966
• Recruitment Status: Unknown
• First Posted: August 2, 2012
• Last Update Posted: January 29, 2014
• Sponsor: Cairo University
• Information provided by (Responsible Party): Hany Shehab, Cairo University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Chronic Hepatitis c	Drug: vitamin D +pegylated interferon + ribavirin; Drug: pegylated interferon + ribavirin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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.
• Study Start Date: May 2012
• Estimated Primary Completion Date: February 2014
• Estimated Study Completion Date: April 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Sustained virologic response [ Time Frame: 72 weeks ]
   Undetectable HCV-RNA 24 weeks after end of treatment.

Secondary Outcome Measures :

1. rapid virologic response [ Time Frame: 4 weeks ]
   undetectable HCV-RNA 4 weeks after commencement of treatment
2. End-of-treatment response [ Time Frame: 48 weeks ]
   undetectable HCV-RNA 48 weeks after commencement of treatment
3. Adverse events [ Time Frame: 72 weeks ]
   Adverse events that could be reasonably and temporally associated with administration of drugs
4. early virologic response [ Time Frame: 12 weeks ]

   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Egypt

National Railway Hospital Center

Cairo, Egypt

Sponsors and Collaborators

Cairo University

Investigators

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

More Information

• Responsible Party: Hany Shehab, Dr, Cairo University
• ClinicalTrials.gov Identifier: NCT01655966
• Other Study ID Numbers: RAIL002
• First Posted: August 2, 2012
• Last Update Posted: January 29, 2014
• Last Verified: January 2014

Keywords provided by Hany Shehab, Cairo University:

chronic hepatitis c; hcv; vitamin d

Additional relevant MeSH terms:

Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Blood-Borne Infections; Communicable Diseases; Flaviviridae Infections; Vitamin D; Interferons; Ribavirin; Vitamins; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action