NCT02057263

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
28

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Apr 2014

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 4, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

February 7, 2014

Completed
2 months until next milestone

Study Start

First participant enrolled

April 1, 2014

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2016

Completed
Last Updated

October 21, 2016

Status Verified

October 1, 2016

Enrollment Period

1.8 years

First QC Date

February 4, 2014

Last Update Submit

October 20, 2016

Conditions

Keywords

VaccineAdjuvantBisphosphonatesAlendronateHepatitis B vaccine

Outcome Measures

Primary Outcomes (1)

  • 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.

    5 months after final alendronate administration/second vaccination

Secondary Outcomes (1)

  • Efficacy

    8 weeks to 5 months after final alendronate dose

Study Arms (2)

Alendronate and Hepatitis B Vaccine

EXPERIMENTAL

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

Drug: AlendronateDrug: Hepatitis B Vaccine

Sugar Pill and Hepatitis B Vaccine

EXPERIMENTAL

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

Drug: Hepatitis B VaccineDrug: Placebo

Interventions

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

Also known as: Fosamax, Bisphosphonate
Alendronate and Hepatitis B Vaccine

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

Also known as: Recombivax
Alendronate and Hepatitis B VaccineSugar Pill and Hepatitis B Vaccine

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

Also known as: Sugar Pill
Sugar Pill and Hepatitis B Vaccine

Eligibility Criteria

Age40 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Hepatitis B

Interventions

AlendronateDiphosphonatesHepatitis B VaccinesRecombivax HBSugars

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitisLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

OrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsViral Hepatitis VaccinesViral VaccinesVaccinesBiological ProductsComplex MixturesCarbohydrates

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

February 4, 2014

First Posted

February 7, 2014

Study Start

April 1, 2014

Primary Completion

February 1, 2016

Study Completion

February 1, 2016

Last Updated

October 21, 2016

Record last verified: 2016-10

Data Sharing

IPD Sharing
Will share

Available upon request

Locations