The Effect of Alendronate on the Immune Response to Hepatitis B Vaccine in Healthy Adults
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.
Drug: Hepatitis B Vaccine
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||The Effect of Alendronate on the Immune Response to Hepatitis B Vaccine in Healthy Adults - a Randomized Placebo-controlled Pilot Study|
- Safety/Adverse events [ Time Frame: 5 months after final alendronate administration/second vaccination ] [ Designated as safety issue: Yes ]Safety is assessed by clinical symptoms and exam at final in-person visit. Standardized CTAE will be recorded and graded (mild/moderate/severe) with a special focus on vaccine related adverse events: Temperature, local injection site reactions, fatigue and malaise, AND adverse events related to alendronate which are primarily gastrointestinal: nausea, vomiting, esophagitis, ulceration. Rare, unlikely events such as atypical fractures and jaw osteonecrosis are extremely unlikely with this duration of dosing (4 weekly doses) but will also be specifically sought.
- Efficacy [ Time Frame: 8 weeks to 5 months after final alendronate dose ] [ Designated as safety issue: No ]Efficacy is assessed by quantitative Anti Hepatitis B Surface IgG (immunoglobulin G) antibody titers in international units (iU) per ml. All subjects must have levels of ZERO in order to participate. A value of 10 iU/ml is considered protective. Titers directed against hepatitis B surface antigen will be measured by commercially available testing Efficacy will also be assessed as a categorical value: Yes/No for protective level of antibody achieved at either 8 weeks or 6 months (5 months after second vaccination). A protective level of hepatitis B surface antibody is defined as 10 iU/ml; levels of 10-100 are considered protective but "poorly responsive." We will compare mean titers between groups (placebo vs. alendronate). We believe a mean increase of 20% is likely clinically significant/important.
|Study Start Date:||February 2014|
|Estimated Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
Experimental: Alendronate and Hepatitis B Vaccine
Participants in the experimental arm will receive 4 alendronate doses during their Hepatitis B vaccination course.
Participants will receive 4 doses of alendronate during the course of the study.
Other Names:Drug: Hepatitis B Vaccine
Participants will receive 3 Hepatitis B vaccinations, according to the schedule outlined by the CDC.
Experimental: Sugar Pill and Hepatitis B Vaccine
Participants in the experimental arm will receive placebo doses during their Hepatitis B vaccination course.
Drug: Hepatitis B Vaccine
Participants will receive 3 Hepatitis B vaccinations, according to the schedule outlined by the CDC.Drug: Placebo
Participants will receive 4 doses of placebo during the course of the study.
Other Name: Sugar Pill
Please refer to this study by its ClinicalTrials.gov identifier: NCT02057263
|Contact: Elizabeth Hohmann, MDfirstname.lastname@example.org|
|Contact: Christina Pindar, BAemail@example.com|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Elizabeth Hohmann, MD 617-724-8625 firstname.lastname@example.org|
|Principal Investigator: Elizabeth Hohmann, MD|
|Sub-Investigator: Ilan Youngster, MD|