Systeemonderzoek naar vaccinresponsen bij veroudering en kwetsbaarheid
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).
Studie Overzicht
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Geschat)
Fase
- Fase 2
Contacten en locaties
Studiecontact
- Naam: Irene Matos, RN
- Telefoonnummer: (203) 737-4739
- E-mail: irene.matos@yale.edu
Studie Locaties
-
-
Connecticut
-
New Haven, Connecticut, Verenigde Staten, 06520
- Werving
- Yale School of Medicine
-
Contact:
- Irene Matos, RN
- Telefoonnummer: (203) 737-4739
- E-mail: irene.matos@yale.edu
-
-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Preventie
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Actieve vergelijker: 21-30 standard dose Fluad
Participants age 21-30 years will receive the standard dose Fluad |
Fluad Quadrivalent, MF59 adjuvanted 0.5 ml intramuscular injection, standard as recommended by manufacturer |
|
Actieve vergelijker: 21-30 high dose Fluzone
Participants age 21-30 years will receive the high dose Fluzone |
Fluzone High-Dose 0.7 ml intramuscular injection, standard as recommended by manufacturer |
|
Experimenteel: ≥65 years standard dose Fluad
Participants age ≥65 years will receive standard dose Fluad |
Fluad Quadrivalent, MF59 adjuvanted 0.5 ml intramuscular injection, standard as recommended by manufacturer |
|
Experimenteel: ≥65 years high dose Fluzone
Participants age ≥65 years will receive high dose Fluzone |
Fluzone High-Dose 0.7 ml intramuscular injection, standard as recommended by manufacturer |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Change in production of IL-6 in monocytes to assess innate immune inflammatory response
Tijdsspanne: Baseline and at Day 2, 7, and 28 post-vaccine
|
Measurement of IL-6 production in monocytes via flow cytometry |
Baseline and at Day 2, 7, and 28 post-vaccine
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Change in Hemagglutination inhibition titer (HAI) in response to vaccination
Tijdsspanne: Baseline and Day 28
|
HAI titers levels in blood measured prior to and at day 28 post-vaccine |
Baseline and Day 28
|
|
Change in transcriptomic analyses of gene expression
Tijdsspanne: At Baseline, Day 2, Day 7, Day 28 and Day 70
|
RNA-seq analysis of RNA derived from peripheral blood mononuclear cells (PBMCs) and platelet-rich plasma (PRP) |
At Baseline, Day 2, Day 7, Day 28 and Day 70
|
|
Change in proteomic analyses
Tijdsspanne: At Baseline, Day 2, Day 7, Day 28 and Day 70
|
Analysis of protein expression using Mass Spectrometry in plasma |
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
Tijdsspanne: At Baseline, Day 2, Day 7, Day 28 and Day 70
|
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. |
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
Tijdsspanne: At Baseline, Day 2, Day 7, Day 28 and Day 70
|
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. |
At Baseline, Day 2, Day 7, Day 28 and Day 70
|
Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Hoofdonderzoeker: Albert Shaw, MD, PhD, Yale University
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- 2000035834
- 0409027018 (Andere identificatie: previous Yale IRB)
- U19AI089992 (Subsidie/contract van de Amerikaanse NIH)
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Beschrijving IPD-plan
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.
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
product vervaardigd in en geëxporteerd uit de V.S.
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .