The Effect of Alendronate on the Immune Response to Hepatitis B Vaccine in Healthy Adults
| Status: | Completed |
|---|---|
| Conditions: | Healthy Studies, Hepatitis, Hepatitis |
| Therapuetic Areas: | Immunology / Infectious Diseases, Other |
| Healthy: | No |
| Age Range: | 40 - 70 |
| Updated: | 4/21/2016 |
| Start Date: | April 2014 |
| End Date: | February 2016 |
The Effect of Alendronate on the Immune Response to Hepatitis B Vaccine in Healthy Adults - a Randomized Placebo-controlled Pilot Study
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.
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.
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.
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.
Inclusion Criteria:
- Subject willing to undergo hepatitis B vaccination AND be randomized to receive 4
doses of alendronate or placebo
- Age 40-70
- Able to consent for self - ascertained by physician assessment at time of history and
exam.
- Chronic stable medical conditions, if well controlled on current therapies are
allowed. For example individuals with well-controlled angina, hypertension, diabetes
on oral agents, treated or past depression or anxiety, COPD, asthma, metabolic
syndrome, NASH, mild chronic renal insufficiency, past history of malignancy, with no
therapy for at least 5 years may be included.
- Willing to use contraception, if a woman of child-bearing potential (WOCBP)
Exclusion Criteria:
- Pregnant, breastfeeding or planning a pregnancy
- Prior Hepatitis B infection OR vaccination
- Autoimmune disorders of any kind (e.g. multiple sclerosis, rheumatoid arthritis,
lupus, Psoriasis etc.)
- HIV or Hepatitis C seropositive
- Any known immunodeficiency (decompensated cirrhosis, HIV/AIDS, prior bone marrow
transplant, or other known immunodeficiency)
- Patients on any immunosuppressive agents including systemic corticosteroids,
calcineurin inhibitors, mTOR inhibitors, lymphocyte depleting biologic agents,
anti-TNF agents, and others; chemotherapeutic anti-neoplastic agents within 5 years.
Stable doses of inhaled corticosteroids for asthma/COPD are allowed.
- Gastroesophageal reflux disease (GERD), peptic ulcer disease, chronic proton pump
inhibitors, chronic antacid use
- Chronic non-steroidal anti-inflammatory use; daily ASA for cardiac prophylaxis is
allowed.
- Esophageal disorders of any kind
- Recent major dental work in the preceding 6 months, excluding dental cleaning and
simple cavity filling
- History of jaw trauma
- Current or prior bisphosphonate use
- Prior history of severe reactions to vaccines
- Yeast or bisphosphonate allergy
- History of hypocalcemia
- Inability to stand or sit upright for at least 30 minutes.
- Any malabsorptive disorder including celiac disease, CF, Inflammatory bowel disease,
recurrent C. difficile colitis, other colitis, prior gastrectomy, bariatric surgery
or chronic diarrhea.
- Diabetes requiring insulin
- Body mass index > 31
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