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The Effect of Alendronate on the Immune Response to Hepatitis B Vaccine in Healthy Adults

Primary Purpose

Hepatitis B

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Alendronate

Hepatitis B Vaccine

Placebo

About this trial

This is an interventional prevention trial for Hepatitis B focused on measuring Vaccine, Adjuvant, Bisphosphonates, Alendronate, Hepatitis B vaccine

Eligibility Criteria

40 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Alendronate and Hepatitis B Vaccine

Sugar Pill and Hepatitis B Vaccine

Arm Description

Participants in the experimental arm will receive 4 alendronate doses during their Hepatitis B vaccination course.

Participants in the experimental arm will receive placebo doses during their Hepatitis B vaccination course.

Outcomes

Primary Outcome Measures

Safety/Adverse events

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.

Secondary Outcome Measures

Efficacy

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.

Full Information

NCT ID

NCT02057263

First Posted

February 4, 2014

Last Updated

October 20, 2016

Sponsor

Massachusetts General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02057263

Brief Title

The Effect of Alendronate on the Immune Response to Hepatitis B Vaccine in Healthy Adults

Official Title

The Effect of Alendronate on the Immune Response to Hepatitis B Vaccine in Healthy Adults - a Randomized Placebo-controlled Pilot Study

Study Type

Interventional

2. Study Status

Record Verification Date

October 2016

Overall Recruitment Status

Completed

Study Start Date

April 2014 (undefined)

Primary Completion Date

February 2016 (Actual)

Study Completion Date

February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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: Evaluating the effect of bisphosphonates on quantitative humoral immune response to hepatitis B vaccine in healthy older volunteers through a randomized clinical trial. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis B

Keywords

Vaccine, Adjuvant, Bisphosphonates, Alendronate, Hepatitis B vaccine

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Alendronate and Hepatitis B Vaccine

Arm Type

Experimental

Arm Description

Participants in the experimental arm will receive 4 alendronate doses during their Hepatitis B vaccination course.

Arm Title

Sugar Pill and Hepatitis B Vaccine

Arm Type

Experimental

Arm Description

Participants in the experimental arm will receive placebo doses during their Hepatitis B vaccination course.

Intervention Type

Drug

Intervention Name(s)

Alendronate

Other Intervention Name(s)

Fosamax, Bisphosphonate

Intervention Description

Participants will receive 4 doses of alendronate during the course of the study.

Intervention Type

Drug

Intervention Name(s)

Hepatitis B Vaccine

Other Intervention Name(s)

Recombivax

Intervention Description

Participants will receive 3 Hepatitis B vaccinations, according to the schedule outlined by the CDC.

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Sugar Pill

Intervention Description

Participants will receive 4 doses of placebo during the course of the study.

Primary Outcome Measure Information:

Title

Safety/Adverse events

Description

Time Frame

5 months after final alendronate administration/second vaccination

Secondary Outcome Measure Information:

Title

Efficacy

Description

Time Frame

8 weeks to 5 months after final alendronate dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Available upon request

Learn more about this trial

The Effect of Alendronate on the Immune Response to Hepatitis B Vaccine in Healthy Adults

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