InfluenzaPhase 2NCT05291676
Systems Investigation of Vaccine Responses in Aging and Frailty
A Phase 2 study testing Fluzone and Fluad in people with Influenza, run by Yale University at 1 site in United States.
Trial summary
This study will compare the immune response signatures (including immunologic, transcriptomic and metabolomic) of the two influenza vaccines approved for use in adults age 65 and over (Fluad and Fluzone High-Dose). Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- Fluzone and Fluad
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Nov 2023to Apr 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 21-40 or 65 and older
- Ability to understand and give informed consent (surrogate consent may apply to nursing home subjects who are decisionally impaired, with verbal assent to be obtained from subject)
- Plan to be in the New Haven, CT area for the next 4-6 weeks
Who cannot join
- Current use of medication, such as antibiotics in past two weeks. To clarify, patients taking antibiotics for the reason of a current acute infection will not be eligible. Those potential participants receiving antibiotics for prophylaxis purposes will be eligible to participate. The intention is not to create a separate group to drawn conclusions, but not to exclude these participants who are not acutely ill.
- Evidence of acute infection, identified by self- report of fever or symptoms in past two weeks
- Treatment for cancer in past three months.
- Previous adverse reaction to influenza vaccine requiring medical attention, such as allergic response (rash, anaphylaxis) or Guillain-Barré syndrome.
- Pregnant/possibly pregnant.
- History of organ, bone marrow or stem cell transplant, liver cirrhosis, kidney disease requiring dialysis, HIV/AIDS, hepatitis C or active hepatitis B
Show all 9Show fewer
- Blood donation of 1 pint or more in past 2 months
- Treatment with clinical trial medication
- Presence of any other condition (e.g., geographical or social), actual or projected, that the investigator feels would restrict or limit the patient's participation for the duration of the study. This provision includes participants who have 50% or more missed appointments in the last three months.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Yale School of Medicine
New Haven, Connecticut, 06520
Irene Matos, RN, 203-737-4739, irene.matos@yale.edu
About this study
This study will compare the immune response signatures (including immunologic, transcriptomic and metabolomic) of the two influenza vaccines approved for use in adults age 65 and over (Fluad and Fluzone High-Dose).
Read the detailed description
There are two vaccines currently approved for use in adults age 65 and greater: a high-dose (HD) influenza vaccine (Fluzone High-Dose) that contains 4 times the hemagglutinin dose found in the standard vaccine, and a standard-dose (SD) vaccine containing the proprietary MF59 adjuvant (Fluad). Both vaccines give significantly highly antibody responses to influenza in older adults. This study will directly compare the HD and SD vaccines in nursing home residents, the population of older adults most vulnerable to influenza outbreaks and morbidity and mortality. It will comprehensively study the innate and adaptive response to vaccination, as well as elucidate transcriptomic and proteomic signatures of vaccine response.
This is a randomized, open label study comparing the two vaccines currently approved for use in adults age ≥ 65 years: the high-dose influenza vaccine and the MF59 adjuvanted standard-dose vaccine, both quadrivalent. The young group will be comprised of individuals 21-30 years of age, and the older cohorts will consist of nursing home residents ≥65 years. Participants will also be evaluated for evidence of influenza-like illness (ILI). ILI is defined to include clinical presentation in older adults: by the presence of either two respiratory symptoms (cough, sore throat, shortness of breath, and nasal stuffiness) or one respiratory and one systemic symptom (headache, malaise, temperature >99° F, report of feverishness and muscle aches, or altered mental status). Diagnoses of influenza will be confirmed using a real-time polymerase chain reaction (PCR) test on a nasopharyngeal (NP) swab specimen done by the hospital Virology Laboratory and facilitated by the participating medical directors.
Although this is neither an efficacy or effectiveness study, participants will be randomized 1:1 to either the high-dose influenza vaccine or the MF59 vaccine within age strata. This will ensure a non-biased allocation of the two vaccines and attempts to balance participant characteristics within age strata.
- Conditions
- Influenza
- Being tested
- Fluzone, Fluad
- Keywords
- vaccine, influenza vaccine, older adults, vaccine response, toll-like receptors, immune response
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluzoneBiological
Fluzone High-Dose 0.7 ml intramuscular injection, standard as recommended by manufacturer
FluadBiological
Fluad Quadrivalent, MF59 adjuvanted 0.5 ml intramuscular injection, standard as recommended by manufacturer
| Study group | Role | What they receive |
|---|---|---|
| 21-30 standard dose Fluad | Active comparator | Participants age 21-30 years will receive the standard dose Fluad Receives: Biological: Fluad |
| 21-30 high dose Fluzone | Active comparator | Participants age 21-30 years will receive the high dose Fluzone Receives: Biological: Fluzone |
| ≥65 years standard dose Fluad | Experimental | Participants age ≥65 years will receive standard dose Fluad Receives: Biological: Fluad |
| ≥65 years high dose Fluzone | Experimental | Participants age ≥65 years will receive high dose Fluzone Receives: Biological: Fluzone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in production of IL-6 in monocytes to assess innate immune inflammatory response
Measurement of IL-6 production in monocytes via flow cytometry
Measured: Baseline and at Day 2, 7, and 28 post-vaccine
Secondary outcomes (5)
Change in Hemagglutination inhibition titer (HAI) in response to vaccination
HAI titers levels in blood measured prior to and at day 28 post-vaccine
Measured: Baseline and Day 28
Change in transcriptomic analyses of gene expression
RNA-seq analysis of RNA derived from peripheral blood mononuclear cells (PBMCs) and platelet-rich plasma (PRP)
Measured: At Baseline, Day 2, Day 7, Day 28 and Day 70
Change in proteomic analyses
Analysis of protein expression using Mass Spectrometry in plasma
Measured: At Baseline, Day 2, Day 7, Day 28 and Day 70
Number of participants with changes in innate immune function from PBMCs and PRP as assessed using flow cytometry
Analyses will include intracellular production of cytokines including IL-10 and TNF-alpha in monocyte populations from PBMCs and expression of platelet activation markers such as CD63 and P-selectin on platelets. The effects of ex vivo Toll-like Receptor stimulation on these parameters will also be assessed.
Measured: At Baseline, Day 2, Day 7, Day 28 and Day 70
Number of participants with changes in B and T cell function from PBMCs as assessed using flow cytometry
This will include analysis of number and proportion of antibody-secreting cells post-vaccine, and analyses of T cells following ex vivo stimulation of PBMCs with influenza hemagglutinins.
Measured: At Baseline, Day 2, Day 7, Day 28 and Day 70
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2022
- Study start6 Nov 2023
- Primary completionApr 2027 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Albert Shaw, MD, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05291676
- Sponsor's protocol ID
- 2000035834
- Other IDs
- U19AI089992, 0409027018
- Status last verified
- Jun 2025
- First submitted
- 7 Mar 2022
- Last updated
- 12 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data with Protected Health Information (PHI) removed on participant demographics and health conditions, and primary and secondary outcome data will be uploaded to the NIH ImmPort as required by the NIH Human Immunology Project Consortium. Publicly available data will be released after publication. Registration on ImmPort required by the NIH. Timeframe for data upload will be approximately 6-12 months after each influenza vaccine season during the study.
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systems Investigation of Vaccine Responses in Aging and Frailty
- ClinicalTrials.gov ID
- NCT05291676
- Acronym / sponsor ID
- 2000035834
- Conditions
- Influenza
- Keywords
- vaccine, influenza vaccine, older adults, vaccine response, toll-like receptors, immune response
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 6 Nov 2023 (actual)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 23 Mar 2022 (actual)
- 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.
This study will compare the immune response signatures (including immunologic, transcriptomic and metabolomic) of the two influenza vaccines approved for use in adults age 65 and over (Fluad and Fluzone High-Dose).
Detailed description
There are two vaccines currently approved for use in adults age 65 and greater: a high-dose (HD) influenza vaccine (Fluzone High-Dose) that contains 4 times the hemagglutinin dose found in the standard vaccine, and a standard-dose (SD) vaccine containing the proprietary MF59 adjuvant (Fluad). Both vaccines give significantly highly antibody responses to influenza in older adults. This study will directly compare the HD and SD vaccines in nursing home residents, the population of older adults most vulnerable to influenza outbreaks and morbidity and mortality. It will comprehensively study the innate and adaptive response to vaccination, as well as elucidate transcriptomic and proteomic signatures of vaccine response.
This is a randomized, open label study comparing the two vaccines currently approved for use in adults age ≥ 65 years: the high-dose influenza vaccine and the MF59 adjuvanted standard-dose vaccine, both quadrivalent. The young group will be comprised of individuals 21-30 years of age, and the older cohorts will consist of nursing home residents ≥65 years. Participants will also be evaluated for evidence of influenza-like illness (ILI). ILI is defined to include clinical presentation in older adults: by the presence of either two respiratory symptoms (cough, sore throat, shortness of breath, and nasal stuffiness) or one respiratory and one systemic symptom (headache, malaise, temperature >99° F, report of feverishness and muscle aches, or altered mental status). Diagnoses of influenza will be confirmed using a real-time polymerase chain reaction (PCR) test on a nasopharyngeal (NP) swab specimen done by the hospital Virology Laboratory and facilitated by the participating medical directors.
Although this is neither an efficacy or effectiveness study, participants will be randomized 1:1 to either the high-dose influenza vaccine or the MF59 vaccine within age strata. This will ensure a non-biased allocation of the two vaccines and attempts to balance participant characteristics within age strata.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 21-30 standard dose Fluad | Active comparator | Biological: FluadParticipants age 21-30 years will receive the standard dose Fluad |
| 21-30 high dose Fluzone | Active comparator | Biological: FluzoneParticipants age 21-30 years will receive the high dose Fluzone |
| ≥65 years standard dose Fluad | Experimental | Biological: FluadParticipants age ≥65 years will receive standard dose Fluad |
| ≥65 years high dose Fluzone | Experimental | Biological: FluzoneParticipants age ≥65 years will receive high dose Fluzone |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age 21-40 or 65 and older
- Ability to understand and give informed consent (surrogate consent may apply to nursing home subjects who are decisionally impaired, with verbal assent to be obtained from subject)
- Plan to be in the New Haven, CT area for the next 4-6 weeks
Key exclusion criteria (9 listed)
- Current use of medication, such as antibiotics in past two weeks. To clarify, patients taking antibiotics for the reason of a current acute infection will not be eligible. Those potential participants receiving antibiotics for prophylaxis purposes will be eligible to participate. The intention is not to create a separate group to drawn conclusions, but not to exclude these participants who are not acutely ill.
- Evidence of acute infection, identified by self- report of fever or symptoms in past two weeks
- Treatment for cancer in past three months.
- Previous adverse reaction to influenza vaccine requiring medical attention, such as allergic response (rash, anaphylaxis) or Guillain-Barré syndrome.
- Pregnant/possibly pregnant.
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 |
|---|---|---|
| FluzoneFluzone High-Dose 0.7 ml intramuscular injection, standard as recommended by manufacturer | Biological | 21-30 high dose Fluzone, ≥65 years high dose Fluzone |
| FluadFluad Quadrivalent, MF59 adjuvanted 0.5 ml intramuscular injection, standard as recommended by manufacturer | Biological | 21-30 standard dose Fluad, ≥65 years standard dose Fluad |
Primary outcome
Change in production of IL-6 in monocytes to assess innate immune inflammatory response
Time frame: Baseline and at Day 2, 7, and 28 post-vaccine
Measurement of IL-6 production in monocytes via flow cytometry
5 secondary outcomes
Change in Hemagglutination inhibition titer (HAI) in response to vaccination
Time frame: Baseline and Day 28
Change in transcriptomic analyses of gene expression
Time frame: At Baseline, Day 2, Day 7, Day 28 and Day 70
Change in proteomic analyses
Time frame: At Baseline, Day 2, Day 7, Day 28 and Day 70
Number of participants with changes in innate immune function from PBMCs and PRP as assessed using flow cytometry
Time frame: At Baseline, Day 2, Day 7, Day 28 and Day 70
Number of participants with changes in B and T cell function from PBMCs as assessed using flow cytometry
Time frame: At Baseline, Day 2, Day 7, Day 28 and Day 70
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2025.
- Individual participant dataSharing planned: Yes. Data with Protected Health Information (PHI) removed on participant demographics and health conditions, and primary and secondary outcome data will be uploaded to the NIH ImmPort as required by the NIH Human Immunology Project Consortium. Publicly available data will be released after publication. Registration on ImmPort required by the NIH. Timeframe for data upload will be approximately 6-12 months after each influenza vaccine season during the study.
Related trials for Influenza
Not yet recruitingPhase 2/3
Evaluation of the Efficacy and Safety of 102D-6 in the Treatment of Acute Uncomplicated Influenza
Influenza, Human
RecruitingPhase 2
COVID-19 Booster and IIV Schedule in Immunocompromised Hosts
COVID 19, Influenza
Not yet recruiting
Family Physician Nudges for Influenza Vaccination Among Older Adults
Influenza Vaccination
Recruiting
Light-based Immunomodulation for Guarding Against Human Respiratory Tract Infections
COVID-19 Respiratory Infection, Influenza
RecruitingPhase 2
BPL-1357 Against H1N1 Influenza Virus Challenge
Influenza, Human
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.
Albert Shaw, MD, PhD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fluzone and Fluad in people with Influenza, run by Yale University 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 3 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 12 Jun 2025. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Irene Matos, RN ((203) 737-4739, irene.matos@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in production of IL-6 in monocytes to assess innate immune inflammatory response (time frame: Baseline and at Day 2, 7, and 28 post-vaccine). 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 12 Jun 2025.