The Effect of Alendronate on the Immune Response to Hepatitis B Vaccine in Healthy Adults
Condition: Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis
Study type: Interventional
Phase: Phase 1

Summary: 
      Vaccines are one of our most effective public health tools but many who need them don't
      respond well and are not protected. Adjuvants boost immune responses and are commonly
      included in vaccine preparations. Bisphosphonates are the most commonly prescribed treatment
      for osteoporosis and may represent a new class of adjuvant. Bisphosphonates are well
      tolerated with chronic administration and have very few adverse effects. Research suggests
      that these medications can stimulate the immune system.

      Bisphosphonates are of special interest in populations with impaired immunity and an
      inability to amount protective antibody responses following immunizations. We propose a pilot
      study to evaluate the clinical relevance of this finding in humans. We will study the effect
      of bisphosphonates on quantitative humoral immune response to hepatitis B vaccine in healthy
      older volunteers who have not previously received this vaccine.
    

Detailed description: 
      Background: Immunization is one of the most beneficial and cost-effective disease prevention
      measures available, but is not always efficacious, especially in older and immunosuppressed
      populations. This commonly encountered failure to produce protective antibodies following
      immunization leaves large parts of the population vulnerable to serious morbidity and
      mortality resulting from potentially preventable communicable diseases. Bisphosphonates, a
      commonly prescribed treatment for osteoporosis that is well tolerated with few adverse
      effects, has recently been shown to enhance B cell expansion and antibody production after
      vaccination in mice, and may represent a new vaccine adjuvant.

      Aims: The purpose of this project is to evaluate the effect of bisphosphonates on the immune
      response to vaccination in adults using two complementary research methodologies:

        1. Evaluating the effect of bisphosphonates on quantitative humoral immune response to
           hepatitis B vaccine in healthy older volunteers through a randomized clinical trial.

        2. Evaluating the effect of bisphosphonate treatment on protection against influenza and
           influenza-like illness after seasonal Influenza immunization in the adult population
           through a population-level retrospective analysis.

      Methods: The first part of the study consists of a randomized, placebo-controlled pilot study
      in which 20 healthy adults 40-70 years of age who are seronegative for Hepatitis B, will be
      randomized to receive either two doses of intramuscular hepatitis B vaccine with alendronate
      or hepatitis B vaccine with placebo. The primary outcome evaluated will be quantitative
      anti-HB surface IgG antibody titers in the study group compared to the placebo group at week
      8 and at 6 months. The second part of the study is a retrospective population based
      case-control study utilizing extensive available data repositories. Rates of influenza,
      influenza-like illness and lower respiratory tract infections per 1000 subjects will be
      ascertained and compared between study and control populations for each year, while adjusting
      for potential confounders.
    

Intervention name(s): Alendronate; Hepatitis B Vaccine; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Participants will receive 4 doses of alendronate during the course of the study.; Participants will receive 3 Hepatitis B vaccinations, according to the schedule outlined by the CDC.; Participants will receive 4 doses of placebo during the course of the study.
Other intervention name(s): Fosamax; Bisphosphonate; Recombivax; Sugar Pill
Intervention MeSH terms: Alendronate; Diphosphonates
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Vaccine; Adjuvant; Bisphosphonates; Alendronate; Hepatitis B vaccine