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A Prospective Study of HBV Immunity and HBV Vaccination in Patients With NAFLD in Canada

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ClinicalTrials.gov Identifier: NCT02985450
Recruitment Status : Recruiting
First Posted : December 7, 2016
Last Update Posted : April 17, 2019
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
GlaxoSmithKline
Information provided by (Responsible Party):
University of Calgary

Tracking Information
First Submitted Date December 1, 2016
First Posted Date December 7, 2016
Last Update Posted Date April 17, 2019
Study Start Date August 2016
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: December 7, 2016)
  • anti-HBs titres (mIU/ml) [ Time Frame: 1 month after completion of the vaccine series ]
    to determine how NAFLD-associated metabolic risk factors and liver inflammation / fibrosis affects vaccine response
  • HBsAg specific B cell response [ Time Frame: 1 month after completion of the vaccine series ]
    to determine how NAFLD-associated metabolic risk factors and liver inflammation / fibrosis affects vaccine response
  • HBsAg specific T cell response [ Time Frame: 1 month after completion of the vaccine series ]
    to determine how NAFLD-associated metabolic risk factors and liver inflammation / fibrosis affects vaccine response
Original Primary Outcome Measures
 (submitted: December 2, 2016)
  • anti-HBs titres (mIU/ml) [ Time Frame: 1 month after completion of the vaccine series ]
    to determine how NAFLD-associated metabolic risk factors and liver inflammation / fibrosis affects vaccine response
  • HBsAg specific T and B cell response [ Time Frame: 1 month after completion of the vaccine series ]
    to determine how NAFLD-associated metabolic risk factors and liver inflammation / fibrosis affects vaccine response
Change History Complete list of historical versions of study NCT02985450 on ClinicalTrials.gov Archive Site
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 A Prospective Study of HBV Immunity and HBV Vaccination in Patients With NAFLD in Canada
Official Title A Prospective Study of Hepatitis B Virus (HBV) Immunity and Hepatitis B Vaccination in Patients With Non Alcoholic Fatty Liver Disease (NAFLD) in Canada
Brief Summary (1) Due to missed childhood vaccination programs, the majority of adult patients with NAFLD in Canada do not have immunity to hepatitis B. (2) Adults with NAFLD who receive the HBV vaccine have reduced immunogenic responses in the setting of obesity (i.e., protective anti-HBs titres). Aims: (1) To determine the sero-prevalence of immunity against hepatitis B in a cohort of prospectively evaluated adult NAFLD patients. (2) To prospectively determine HBV vaccine responses (anti-HBs titres) in adult NAFLD patients.
Detailed Description

The hepatitis B virus (HBV) is truly a global human pathogen that affects at least 2 billion people worldwide including ~240 million chronic hepatitis B (CHB) carriers that are at risk for end-stage liver disease. The diagnosis of CHB is confirmed by the persistence of the HBV surface antigen (HBsAg) in serum for >6 months. However, a latent form of HBV infection known as occult hepatitis B infection (OBI) characterized by low-level viremia (i.e., HBV DNA < 200 IU/ml) despite undetectable serum HBsAg has been described with unclear clinical consequences.

A safe and effective HBV vaccine has been available for ~3 decades and consists of recombinant HBsAg which contains the major viral antigenic epitopes and induces a protective neutralizing antibody to HBsAg (anti-HBs) response in >85% of children vaccinated. Canada is a low HBV-endemic region and in Alberta, and Ontario, public health uses maternal screening for HBsAg to identify babies at-risk for CHB. Thus, all infants born to HBsAg (+) mothers are given passive-active immunoprophylaxis with hepatitis B immune globulin (HBIG) and the HBV vaccine within 12 hours of birth, as well as 2 doses at ~2 and ~6 months of age. Testing of the infants for anti-HBs is recommended at 9 months to ensure immunity. In the late 1990's, a universal HBV childhood vaccination program was initiated in all Canadian provinces and jurisdictions. In Alberta and in Ontario, school-age children are scheduled to receive the 3-dose HBV vaccine series in grade 5. However there remain a significant proportion of adult Canadians (i.e., born before 1985) who missed childhood vaccination programs. Although current guidelines recommend that certain high-risk populations receive hepatitis B immunization, appropriate identification and compliance is generally much lower in adults compared to children.

According to the most recent Canadian Association for the Study of Liver Disease guidelines, all adults with diabetes, as well as all patients with chronic liver disease should receive the hepatitis B vaccine. The basis for these recommendations are two-fold, (1) diabetics may be at risk of blood-borne virus (BBV) exposure through contact with contaminated blood glucose monitoring devices and (2) diabetic patients are at increased risk of the metabolic syndrome and the development of non-alcoholic fatty liver disease (NAFLD). The improvement in blood glucose monitoring devices, and increased knowledge has reduced the risk of HBV exposure in patients with diabetes. Further, the investigators' initial seroepidemiological survey of acute HBV outbreaks in Alberta revealed a decreasing prevalence in diabetic patients. Therefore the main incentive for HBV vaccination in diabetics is due to the concomitant risk of the metabolic syndrome and advanced liver disease due to NAFLD. There is limited data on HBV vaccination in NAFLD patients. Further studies are required in a North American adult (Canadian population).

The investigators propose that adults with NAFLD should undergo comprehensive screening for hepatitis B immunogenicity, in addition to screening for infection, and catch up or booster vaccinations should be administered to non-immunized patients with confirmatory immunity testing thereafter.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
PBMCs will be cryopreserved to assess HBV specific T and B cell responses.
Sampling Method Non-Probability Sample
Study Population NAFLD patients will be recruited from large tertiary liver clinics in Canada
Condition
  • Non-Alcoholic Fatty Liver Disease
  • Hepatitis B
  • Vaccine Reaction
Intervention Biological: Engerix-B
Hepatitis B Vaccine
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: December 2, 2016)
300
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Subjects 18-60 years of age, who provide signed informed consent
  • Diagnosis of NAFLD/NASH according to expert assessment (by imaging, TE, abnormal lab tests and/or liver biopsy)
  • No evidence of prior infection or immunity to hepatitis B (negative HBsAg, anti-HBs, anti-HBc).

Exclusion Criteria:

  • Subjects < 18 years of age,
  • Subjects who refused vaccination
  • Have documented immunity / prior exposure to hepatitis B (i.e., positive for ant-HBs, anti-HBc, HBsAg)
  • Pregnancy
  • HIV-positive
  • Decompensated cirrhosis (i.e., Child-Pugh Class B or C) due to impact on immune response.
  • Subjects >60 y will be excluded, due to effect of age and reduced response to HBV vaccination.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Sarah Haylock-Jacobs 403-220-7808 shaylock@ucalgary.ca
Listed Location Countries Canada
Removed Location Countries  
 
Administrative Information
NCT Number NCT02985450
Other Study ID Numbers REB16-0274
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party University of Calgary
Study Sponsor University of Calgary
Collaborators
  • Canadian Institutes of Health Research (CIHR)
  • GlaxoSmithKline
Investigators
Principal Investigator: Carla Coffin University of Calgary
PRS Account University of Calgary
Verification Date June 2018