InfluenzaPhase 4NCT03603509
Gene Signatures of Influenza Vaccine Responses in Older Adults
A Phase 4 study testing Fluad Vaccine and Fluzone High-Dose in people with Influenza, run by Mayo Clinic at 1 site in United States.
Trial summary
The purpose of this research study is to better understand the immune response to the Adjuvanted Subunit flu vaccine (MF59) and the High Dose flu vaccine (HDFlu) in people 65 years of age and older. The research team will be studying why immune response diminishes as people get older in both men and women. Read more about this study
- Who is it for?
- Ages 65 years and olderHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- Fluad Vaccine and Fluzone High-Dose
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 241 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Aug 2018to 2 Jan 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Male or female adults ages 18-40 or of 65 and or older at the time of enrollment
- Eligible to receive Fluad® (MF59Flu) or Fluzone® (HDFlu) if age 65 or older
- No history of anaphylactic reaction to gelatin, neomycin, or other vaccine component
- Not pregnant
- No immunosuppression or immunodeficiency
- No acute illness at time of vaccination
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- Determined by medical history and clinical judgment to be eligible for the study, by being generally healthy, with no autoimmune or immunosuppressive conditions and having stable current medical conditions (subjects with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease 12 weeks before receipt of study vaccine, will be eligible. A change in dose or therapy within a category (e.g., change from one nonsteroidal anti-inflammatory drug to another) is allowed. A change to a new therapy category (e.g., surgery or addition of a new pharmacological class) is only allowed if it is not caused by worsening disease. A change to a new therapy category caused by worsening disease is considered significant and therefore ineligible for enrollment.
- Patients with diabetes mellitus are eligible for inclusion if they have had a hemoglobin A1c measurement of <8.0 within the past 6 months prior to enrollment. These hemoglobin A1c measurements are recommended at least twice yearly by the American Diabetes Association (ADA), and the target levels here are representative of the goals of the ADA. These hemoglobin A1c levels will ensure that these participants have good glycemic control. (American Diabetes Association. American Diabetes Association Position Statement: Standards of Medical Care in Diabetes- 2015. Diabetes Care 2015;38(Suppl. 1): S1-S94)
- Able to follow study procedures in the opinion of the investigator
- Expected to be available for the duration of the study
- Weighs >110 lbs
Who cannot join
- Known or suspected immunodeficiency or receiving treatment with immunosuppressive therapy including cytotoxic agents or systemic corticosteroids (e.g., for cancer, HIV, or autoimmune disease). If systemic corticosteroids have been administered short term for treatment of an acute illness, subjects will be included if corticosteroid therapy (inhaled, intranasal, and intra-articular corticosteroid therapy is permitted) has been discontinued for at least 30 days.
- Serious chronic medical conditions including metastatic malignancy, severe chronic obstructive pulmonary disease requiring supplemental oxygen, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder that, in the investigator's opinion, precludes the subject from participating in the study. Diabetic patients will be excluded if they do not have a hemoglobin A1c measurement within the past 6 months or if they had a hemoglobin A1c measurement of an A1c >8.0
- Receipt of any blood products, including immunoglobulin, within 6 months of study enrollment.
- Current anticoagulant therapy or a history of bleeding diathesis that would contraindicate intramuscular (IM) injection. (Note: antiplatelet drugs such as aspirin and clopidogrel are permitted.)
- Receipt of any vaccines within the past 30 days prior to enrollment
- Receipt of the current seasonal influenza vaccine other than in this study
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- Acute illness within the last 30 days
- Blood donation within the last 58 days prior to study enrollment
- Any medical condition that would, in the opinion of the investigator, interfere with the evaluation of the study objectives
- Pregnant patients will be excluded
- Any condition (e.g. allergic reaction, Guillain-Barre Syndrome) that precludes their receipt of the influenza vaccine
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: Transcriptomic Signatures of Influenza Vaccine Responses
The purpose of this research study is to better understand the immune response to the Adjuvanted Subunit flu vaccine (MF59) and the High Dose flu vaccine (HDFlu) in people 65 years of age and older. The research team will be studying why immune response diminishes as people get older in both men and women. The ultimate goal is to understand how flu immunity develops after vaccination. This information may lead to the development of more effective flu vaccines in the future.
Read the detailed description
The overall goal of this proposal is to determine how vaccine type, sex, and gene expression influence both innate and T helper cell immune responses using systems biology and bioinformatics as tools to comprehensively assess the human transcriptome. We will evaluate sex-dependent immune responses to two unique influenza vaccines in a population of older adults; the recently FDA-licensed MF59-adjuvanted influenza subunit vaccine and the high-dose split virion influenza virus vaccine. The influence of sex on immune response to vaccination has been observed across multiple vaccines (including standard dose influenza vaccines, but the mechanisms are unknown, it affects all age groups regardless of hormonal status, and existing studies focus almost exclusively on humoral immune responses. Relatively little is known about the effect of sex on innate and T helper responses following vaccination and we are unaware of any studies evaluating the effect of sex on immune responses to adjuvanted influenza vaccine. The presence of adjuvant (MF59Flu) or higher antigen (Ag) dose leads to greater immunogenicity through mechanisms that have not been fully deciphered and are likely to be different. Further, a direct comparison of innate and T helper immune responses between adjuvanted and high dose influenza vaccines has not been reported.
The study design will include 200 generally healthy individuals (ages ≥65) who meet all inclusion criteria. 100 subjects will receive each vaccine with equal sex representation in each subgroup (a factorial design for sex by vaccine type). Subjects will undergo venipuncture for blood samples (~100 mL each, sufficient for the proposed assays) before vaccination and at three timepoints after vaccination (Day 1, Day 8, Day 28).
The clinical characterization of our study subjects will include demographic information, height, weight, BMI, waist circumference, medications, and medical conditions that do not meet exclusion criteria (see Protection of Human Subjects). We will also quantify blood leukocyte populations (CBC, WBC differential).
Immunosenescence and cytomegalovirus (CMV) infection can affect influenza vaccine-induced immune responses. We will evaluate whether CMV seropositivity or other measures of immunosenescence are associated with immune response and whether they interact with vaccine type/sex.
We will monitor/characterize transcriptional changes (mRNA and miRNA) as well as measures of immune function (cytokine secretion, leukocyte surface phenotype, hemagglutination inhibiting antibody titer, and memory B cell ELISPOT) at each time point.
- Conditions
- Influenza
- Being tested
- Fluad Vaccine, Fluzone High-Dose
- Keywords
- Fluad, MF59, Fluzone, HDFlu, Influenza, Vaccine
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluad VaccineDrug
Also called adjuvanted influenza vaccine
FLUAD is an inactivated influenza vaccine indicated for active immunization against influenza. disease caused by influenza virus subtypes A and type B contained in the vaccine. FLUAD is. approved for use in persons 65 years of age and older.
Fluzone High-DoseDrug
Also called high dose influenza vaccine
FLUZONE® HIGH-DOSE vaccine is indicated for people 65 years of age and older to help prevent influenza disease caused by influenza A and B strains contained in the vaccine.
| Study group | Role | What they receive |
|---|---|---|
| Fluad vaccine | Active comparator | Subjects receive a single dose of the Fluad influenza vaccine. Receives: Drug: Fluad Vaccine |
| Fluzone vaccine | Active comparator | Subjects receive a single dose of the Fluzone High-Dose influenza vaccine. Receives: Drug: Fluzone High-Dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Innate Cell IFNa2a Production
Cytokine secretion (interferon alpha 2a) after in vitro stimulation with influenza virus
Measured: Baseline, Day 1
Hemagglutination Inhibition Ab Titer
Reciprocal of the serum dilution exhibiting no hemagglutination (the larger the number, the more agglutinating antibodies the subject has. A titer of equal to more than 1:40 and above is considered a protective antibody titer)
Measured: Baseline and Day 28
T Cell Gene Expression
Gene expression counts. The number shown is the total number of RNA molecules whose sequence matches a human gene. This is a measure of how much gene expression is occurring in the cells in each subject's blood sample.
Measured: Baseline, Day 28
T Cell miRNA Expression
Next generation sequencing of purified T cells' miRNA
Measured: Baseline, Day 8, Day 28
Innate IFNAR1 Cell Gene Expression
IFNAR1 gene counts (the number of molecules of RNA whose sequence matches the interferon alpha receptor 1 gene that were present in the subject's blood sample).
Measured: Baseline, Day 8
Innate Cell miRNA Expression
Next generation sequencing of purified innate cells' miRNA
Measured: Baseline, Day 1, Day 8
Memory B Cell ELISPOT
Number of influenza-specific Ab producing memory B cells. Spot Forming Units (SFUs) are the frequency of Ab secreting B cells in an ELISPOT assay.
Measured: Day 28
Secondary outcomes (5)
T Cell ELISPOT Response
influenza-specific, IFNg producing, memory T cells. Spot Forming Units (SFUs) are the frequency of IFN-g secreting T cells in an ELISPOT assay.
Measured: Day 28
T Cell Phenotype
Flow cytometry analysis of T cells. The results show the percentage of specific white blood cell types are present in each subject's blood sample. Reported as a % of the total peripheral blood mononuclear cells.
Measured: Day 28
Innate Cell Phenotype
Flow cytometry analysis of innate cells. The results show the percentage of classical monocytes in each subject's blood sample. The data are reported as a percentage of the peripheral blood mononuclear cells.
Measured: Day 1 (stim)
CMV Serostatus
Serum CMV-specific IgG level. Number reported as Sample Index (the optical density in an ELISA). The Sample Index is a semi-quantitative measure of how much CMV-specific IgG antibodies are in each subject's blood sample. The values range from 0 to 4. Values between 0 and 3 are relative measures of the amount of antibody (0 = no antibody, 1 = a low level of antibody, 3 = a high level of antibody). Values from 3-4 all reflect high levels of antibody but typically exceed the linear range of the assay and cannot be used to quantify exact amounts of antibody.
Measured: Baseline
CD4/CD8 Ratio
Flow cytometry analysis of T cells. The results show the ratio of CD4+ T cells compared to CD8+ T cells present in each subject's PBMCs.
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2018
- Study start27 Aug 2018
- Primary completion2 Jan 2019
- Study completion2 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Eligible subjects who consent and enroll will be randomly assigned to receive either the Fluad Vaccine or Fluzone High-Dose vaccine.
- Masking
- None (open label)
- Enrolment
- 241 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Richard B. Kennedy, Mayo Clinic
- Investigators
- Richard B Kennedy, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03603509
- Sponsor's protocol ID
- 17-010601
- Other IDs
- R01AI132348
- Status last verified
- Apr 2023
- First submitted
- 18 Jul 2018
- Last updated
- 16 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcriptomic Signatures of Influenza Vaccine Responses
- ClinicalTrials.gov ID
- NCT03603509
- Acronym / sponsor ID
- 17-010601
- Conditions
- Influenza
- Keywords
- Fluad, MF59, Fluzone, HDFlu, Influenza, Vaccine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 241 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 27 Aug 2018 (actual)
- Primary completion
- 2 Jan 2019 (actual)
- Study completion
- 2 Jan 2019 (actual)
- First posted
- 27 Jul 2018 (actual)
- Results
- Posted 16 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to better understand the immune response to the Adjuvanted Subunit flu vaccine (MF59) and the High Dose flu vaccine (HDFlu) in people 65 years of age and older. The research team will be studying why immune response diminishes as people get older in both men and women. The ultimate goal is to understand how flu immunity develops after vaccination. This information may lead to the development of more effective flu vaccines in the future.
Detailed description
The overall goal of this proposal is to determine how vaccine type, sex, and gene expression influence both innate and T helper cell immune responses using systems biology and bioinformatics as tools to comprehensively assess the human transcriptome. We will evaluate sex-dependent immune responses to two unique influenza vaccines in a population of older adults; the recently FDA-licensed MF59-adjuvanted influenza subunit vaccine and the high-dose split virion influenza virus vaccine. The influence of sex on immune response to vaccination has been observed across multiple vaccines (including standard dose influenza vaccines, but the mechanisms are unknown, it affects all age groups regardless of hormonal status, and existing studies focus almost exclusively on humoral immune responses. Relatively little is known about the effect of sex on innate and T helper responses following vaccination and we are unaware of any studies evaluating the effect of sex on immune responses to adjuvanted influenza vaccine. The presence of adjuvant (MF59Flu) or higher antigen (Ag) dose leads to greater immunogenicity through mechanisms that have not been fully deciphered and are likely to be different. Further, a direct comparison of innate and T helper immune responses between adjuvanted and high dose influenza vaccines has not been reported.
The study design will include 200 generally healthy individuals (ages ≥65) who meet all inclusion criteria. 100 subjects will receive each vaccine with equal sex representation in each subgroup (a factorial design for sex by vaccine type). Subjects will undergo venipuncture for blood samples (~100 mL each, sufficient for the proposed assays) before vaccination and at three timepoints after vaccination (Day 1, Day 8, Day 28).
The clinical characterization of our study subjects will include demographic information, height, weight, BMI, waist circumference, medications, and medical conditions that do not meet exclusion criteria (see Protection of Human Subjects). We will also quantify blood leukocyte populations (CBC, WBC differential).
Immunosenescence and cytomegalovirus (CMV) infection can affect influenza vaccine-induced immune responses. We will evaluate whether CMV seropositivity or other measures of immunosenescence are associated with immune response and whether they interact with vaccine type/sex.
We will monitor/characterize transcriptional changes (mRNA and miRNA) as well as measures of immune function (cytokine secretion, leukocyte surface phenotype, hemagglutination inhibiting antibody titer, and memory B cell ELISPOT) at each time point.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Eligible subjects who consent and enroll will be randomly assigned to receive either the Fluad Vaccine or Fluzone High-Dose vaccine.
| Arm | Type | Receives |
|---|---|---|
| Fluad vaccine | Active comparator | Drug: Fluad VaccineSubjects receive a single dose of the Fluad influenza vaccine. |
| Fluzone vaccine | Active comparator | Drug: Fluzone High-DoseSubjects receive a single dose of the Fluzone High-Dose influenza vaccine. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (11 listed)
- Male or female adults ages 18-40 or of 65 and or older at the time of enrollment
- Eligible to receive Fluad® (MF59Flu) or Fluzone® (HDFlu) if age 65 or older
- No history of anaphylactic reaction to gelatin, neomycin, or other vaccine component
- Not pregnant
- No immunosuppression or immunodeficiency
Key exclusion criteria (11 listed)
- Known or suspected immunodeficiency or receiving treatment with immunosuppressive therapy including cytotoxic agents or systemic corticosteroids (e.g., for cancer, HIV, or autoimmune disease). If systemic corticosteroids have been administered short term for treatment of an acute illness, subjects will be included if corticosteroid therapy (inhaled, intranasal, and intra-articular corticosteroid therapy is permitted) has been discontinued for at least 30 days.
- Serious chronic medical conditions including metastatic malignancy, severe chronic obstructive pulmonary disease requiring supplemental oxygen, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder that, in the investigator's opinion, precludes the subject from participating in the study. Diabetic patients will be excluded if they do not have a hemoglobin A1c measurement within the past 6 months or if they had a hemoglobin A1c measurement of an A1c >8.0
- Receipt of any blood products, including immunoglobulin, within 6 months of study enrollment.
- Current anticoagulant therapy or a history of bleeding diathesis that would contraindicate intramuscular (IM) injection. (Note: antiplatelet drugs such as aspirin and clopidogrel are permitted.)
- Receipt of any vaccines within the past 30 days prior to enrollment
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 |
|---|---|---|
| Fluad VaccineAlso: adjuvanted influenza vaccineFLUAD is an inactivated influenza vaccine indicated for active immunization against influenza. disease caused by influenza virus subtypes A and type B contained in the vaccine. FLUAD is. approved for use in persons 65 years of age and older. | Drug | Fluad vaccine |
| Fluzone High-DoseAlso: high dose influenza vaccineFLUZONE® HIGH-DOSE vaccine is indicated for people 65 years of age and older to help prevent influenza disease caused by influenza A and B strains contained in the vaccine. | Drug | Fluzone vaccine |
Primary outcome
Innate Cell IFNa2a Production
Time frame: Baseline, Day 1
Cytokine secretion (interferon alpha 2a) after in vitro stimulation with influenza virus
Hemagglutination Inhibition Ab Titer
Time frame: Baseline and Day 28
Reciprocal of the serum dilution exhibiting no hemagglutination (the larger the number, the more agglutinating antibodies the subject has. A titer of equal to more than 1:40 and above is considered a protective antibody titer)
T Cell Gene Expression
Time frame: Baseline, Day 28
Gene expression counts. The number shown is the total number of RNA molecules whose sequence matches a human gene. This is a measure of how much gene expression is occurring in the cells in each subject's blood sample.
T Cell miRNA Expression
Time frame: Baseline, Day 8, Day 28
Next generation sequencing of purified T cells' miRNA
Innate IFNAR1 Cell Gene Expression
Time frame: Baseline, Day 8
IFNAR1 gene counts (the number of molecules of RNA whose sequence matches the interferon alpha receptor 1 gene that were present in the subject's blood sample).
Innate Cell miRNA Expression
Time frame: Baseline, Day 1, Day 8
Next generation sequencing of purified innate cells' miRNA
Memory B Cell ELISPOT
Time frame: Day 28
Number of influenza-specific Ab producing memory B cells. Spot Forming Units (SFUs) are the frequency of Ab secreting B cells in an ELISPOT assay.
5 secondary outcomes
T Cell ELISPOT Response
Time frame: Day 28
T Cell Phenotype
Time frame: Day 28
Innate Cell Phenotype
Time frame: Day 1 (stim)
CMV Serostatus
Time frame: Baseline
CD4/CD8 Ratio
Time frame: Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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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.
Richard B Kennedy principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fluad Vaccine and Fluzone High-Dose in people with Influenza, run by Mayo Clinic 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 11 inclusion and 11 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 16 May 2023. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Innate Cell IFNa2a Production (time frame: Baseline, Day 1). The study lists 7 primary outcomes in all. 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 16 May 2023.