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Platelet Immune Responses in Aging and Influenza and Sepsis (INVACS)

9. august 2019 oppdatert av: Samuel Brown, Intermountain Health Care, Inc.

Aging is associated with immunosenescence and impaired host defense mechanisms, contributing to influenza-related morbidity and mortality. Preliminary data demonstrate that the platelet transcriptome is markedly different between healthy subjects and influenza patients. Interferon-induced transmembrane proteins (IFITM) family members are among the transcripts significantly increased in platelets during influenza and expression of IFITM-3 is impaired in elderly subjects, a pattern associated with increased mortality. This study will build on these data and investigate if aging influences the expression of platelet IFITM family members in patients with influenza and sepsis.

This study will prospectively determine if aging alters the induction of (IFITMs) in platelets from hospitalized influenza and sepsis patients. The study will also determine if diminished expression of IFITM family members correlates with an increased risk of adverse outcomes in older influenza and sepsis patients.

Studieoversikt

Status

Ukjent

Forhold

Detaljert beskrivelse

This will be a prospective observational cohort study comparing older (age≥65) and younger (age<65) influenza and sepsis patients.

Studietype

Observasjonsmessig

Registrering (Forventet)

150

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Forente stater
    • Utah
      • Murray, Utah, Forente stater, 84107
        • Intermountain Medical Center

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Prøvetakingsmetode

Ikke-sannsynlighetsprøve

Studiepopulasjon

This will be a prospective observational cohort study comparing older (age≥65) and younger (age<65) influenza and sepsis patients.

Beskrivelse

Inclusion Criteria:

  • ≥18 years old at the time of enrollment
  • Meet one of the following three main criteria:

A. INFLUENZA (AND OTHER RESPIRATORY VIRUS) PATIENTS:

Patients admitted to the intensive care unit (ICU) with a primary microbiologic diagnosis of influenza (any strain) or other routinely clinically identified respiratory viruses within 1 week of symptom onset. Influenza or other respiratory virus will be diagnosed using an RT-PCR viral panel on a respiratory tract specimen, as is currently standard of care on patients admitted to the ICUs at IMC with respiratory symptoms.

OR

B. SEPSIS PATIENTS:

Sepsis patients must have

  1. Suspected or confirmed infection

    AND

  2. Organ dysfunction as defined by a SOFA >= 2 above baseline (if no baseline data available, SOFA assumed to be 0)

OR

C. SEPTIC SHOCK PATIENTS:

AFTER INFUSION OF 20ML/KG CRYSTALLOID OR EQUIVALENT, Septic shock patients must have

  1. Suspected or confirmed infection

    AND

  2. Lactate > 2 mmol/L

    AND

  3. Receiving vasopressors

    • All patients must be enrolled into the study within 72 hours of ICU admission

Exclusion criteria

  • Have a congenital or acquired immunodeficiency disorder (e.g., chronic variable immune deficiency, agammaglobulinemia, hypogammaglobulinemia, leukocyte adhesion defects, IgA deficiency, etc.)
  • Have neutropenia (<1,000/mm3)
  • Have received immunosuppressant medications within the previous 30 days (e.g., prednisone or prednisone equivalent at a dose≥10mg daily for ≥14 days or any cyclosporine, TNF-alpha antagonists, tacrolimus, sirolimus, interferons, mycophenolate, biological agents, methotrexate, azathioprine, polyclonal/monoclonal antibodies, etc.)
  • Have any history of bone marrow or organ transplantation
  • Have an active malignancy (not including non-melanoma skin cancer or localized prostate cancer), or have received chemotherapy drugs within the last 6 months.
  • Have been admitted to the ICU for greater than 72 hours
  • Have a Hemoglobin level <7gm/dl
  • Have clinically significant bleeding

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

Kohorter og intervensjoner

Gruppe / Kohort
Influenza/respiratory virus pts <65 yrs
Patients with a primary microbiologic diagnosis of influenza (any strain) or other routinely clinically identified respiratory viruses
Influenza/respiratory virus pts ≥ 65 yrs
Patients with a primary microbiologic diagnosis of influenza (any strain) or other routinely clinically identified respiratory viruses
Sepsis/septic shock patients < 65 yrs
Sepsis and septic shock patients
Sepsis/septic shock patients ≥ 65 yrs
sepsis and septic shock patients

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
90 day mortality
Tidsramme: 90 days
For the increased risk of mortality outcome, 90-day mortality will be the primary outcome variable. This will be modeled using mixed effects logistic regression, using days 0, 3, and 7 as repeated measurements. In this fashion, IFITM-3 and mortality are time-varying. A separate model will be fitted for the younger and older groups, since age group is expected to be collinear with IFITM-3 protein.
90 days

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
28 day mortality
Tidsramme: 28 days
The same sample of influenza patients will be used for mortality analysis. Based on published and unpublished data, 28-day mortality in critically-ill influenza patients admitted to ICUs ranges from 10-40%, even during non-pandemic periods. Based on these estimates, our sample size (n=75 younger and n=75 older) provides 84% power (two-sided alpha 0.05 comparison) to detect a difference in incidence of 29% and 9%, which is a conservative estimate of the difference between the younger and older groups.
28 days
Interferon-induced transmembrane protein expression in platelets
Tidsramme: 24(±12) hours of diagnosis (day 0 or 1), day 3, 5, and 90
Recent evidence also demonstrates that IFITM-3 acts as a membrane organizer by facilitating clathrin-mediated endocytosis (CME). This membrane-organizing process allows cells to internalize molecules and viruses. CME regulates platelet membrane organization. IFITM-3 is demonstrated as necessary for host defenses against influenza virus. Moreover, with absent or reduced levels of IFITM-3, cells do not effectively restrict viral replication, an impaired response that may influence adverse clinical outcomes.
24(±12) hours of diagnosis (day 0 or 1), day 3, 5, and 90
IFITM-3 mRNA
Tidsramme: 24(±12) hours of diagnosis (day 0 or 1), day 3, 5, and 90.

Platelet IFITM-3 protein levels have been seen to be increased in influenza patients and correlated with IFITM-3 mRNA (r2=0.33, p<0.005). However, in hospitalized influenza patients, platelet IFITM-3 mRNA and protein expression was decreased in older, compared to young patients.

It is hypothesized that influenza will induce expression of IFITM family members in platelets; IFITM's expression will be reduced in older compared to young influenza patients. This hypothesis will be tested to determine whether or not influenza induces IFITM-3 expression in human platelets and compare older and young subjects. Here, an outcome of IFITM-3 protein will be tracked in conjunction with mRNA.
24(±12) hours of diagnosis (day 0 or 1), day 3, 5, and 90.

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Intermountain Health Care, Inc.

Samarbeidspartnere

University of Utah

Etterforskere

  • Hovedetterforsker: Samuel M Brown, MD MS, Intermountain Health Care, Inc.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

21. desember 2014

Primær fullføring (Forventet)

1. oktober 2019

Studiet fullført (Forventet)

1. desember 2019

Datoer for studieregistrering

Først innsendt

3. januar 2017

Først innsendt som oppfylte QC-kriteriene

3. januar 2017

Først lagt ut (Anslag)

5. januar 2017

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

13. august 2019

Siste oppdatering sendt inn som oppfylte QC-kriteriene

9. august 2019

Sist bekreftet

1. august 2019

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 1040298

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

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