Hepatitis BPhase 1NCT02057263
The Effect of Alendronate on the Immune Response to Hepatitis B Vaccine in Healthy Adults
A Phase 1 study testing Alendronate and Hepatitis B Vaccine in people with Hepatitis B, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis B
- What is being tested?
- Alendronate and Hepatitis B Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2014to Feb 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: 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.
Read the 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.
- Conditions
- Hepatitis B
- Being tested
- Alendronate, Hepatitis B Vaccine, Placebo
- Keywords
- Vaccine, Adjuvant, Bisphosphonates, Alendronate, Hepatitis B vaccine
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlendronateDrug
Also called Fosamax, Bisphosphonate
Participants will receive 4 doses of alendronate during the course of the study.
Hepatitis B VaccineDrug
Also called Recombivax
Participants will receive 3 Hepatitis B vaccinations, according to the schedule outlined by the CDC.
PlaceboDrug
Also called Sugar Pill
Participants will receive 4 doses of placebo during the course of the study.
| Study group | Role | What they receive |
|---|---|---|
| Alendronate and Hepatitis B Vaccine | Experimental | Participants in the experimental arm will receive 4 alendronate doses during their Hepatitis B vaccination course. Receives: Drug: Alendronate; Drug: 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. Receives: Drug: Hepatitis B Vaccine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 months after final alendronate administration/second vaccination
Secondary outcomes (1)
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.
Measured: 8 weeks to 5 months after final alendronate dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2014 (estimated)
- Study startApr 2014
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis BStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elizabeth L. Hohmann, MD, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02057263
- Sponsor's protocol ID
- 2014-P-000040
- Status last verified
- Oct 2016
- First submitted
- 4 Feb 2014
- Last updated
- 21 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Available upon request
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Alendronate on the Immune Response to Hepatitis B Vaccine in Healthy Adults - a Randomized Placebo-controlled Pilot Study
- ClinicalTrials.gov ID
- NCT02057263
- Acronym / sponsor ID
- 2014-P-000040
- Conditions
- Hepatitis B
- Keywords
- Vaccine, Adjuvant, Bisphosphonates, Alendronate, Hepatitis B vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 7 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alendronate and Hepatitis B Vaccine | Experimental | Drug: Alendronate, Drug: Hepatitis B VaccineParticipants in the experimental arm will receive 4 alendronate doses during their Hepatitis B vaccination course. |
| Sugar Pill and Hepatitis B Vaccine | Experimental | Drug: Hepatitis B Vaccine, Drug: PlaceboParticipants in the experimental arm will receive placebo doses during their Hepatitis B vaccination course. |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (19 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlendronateAlso: Fosamax, BisphosphonateParticipants will receive 4 doses of alendronate during the course of the study. | Drug | Alendronate and Hepatitis B Vaccine |
| Hepatitis B VaccineAlso: RecombivaxParticipants will receive 3 Hepatitis B vaccinations, according to the schedule outlined by the CDC. | Drug | Alendronate and Hepatitis B Vaccine, Sugar Pill and Hepatitis B Vaccine |
| PlaceboAlso: Sugar PillParticipants will receive 4 doses of placebo during the course of the study. | Drug | Sugar Pill and Hepatitis B Vaccine |
Primary outcome
Safety/Adverse events
Time frame: 5 months after final alendronate administration/second vaccination
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.
1 secondary outcome
Efficacy
Time frame: 8 weeks to 5 months after final alendronate dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2016.
- Individual participant dataSharing planned: Yes. Available upon request
Related trials for Hepatitis B
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Alendronate and Hepatitis B Vaccine in people with Hepatitis B, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety/Adverse events (time frame: 5 months after final alendronate administration/second vaccination). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2016.