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

9 de agosto de 2019 actualizado por: 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.

Descripción general del estudio

Estado

Desconocido

Condiciones

Descripción detallada

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

Tipo de estudio

De observación

Inscripción (Anticipado)

150

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

    • Utah
      • Murray, Utah, Estados Unidos, 84107
        • Intermountain Medical Center

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Método de muestreo

Muestra no probabilística

Población de estudio

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

Descripción

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

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

Cohortes e Intervenciones

Grupo / Cohorte
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

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
90 day mortality
Periodo de tiempo: 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

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
28 day mortality
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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.

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Colaboradores

Investigadores

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

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

21 de diciembre de 2014

Finalización primaria (Anticipado)

1 de octubre de 2019

Finalización del estudio (Anticipado)

1 de diciembre de 2019

Fechas de registro del estudio

Enviado por primera vez

3 de enero de 2017

Primero enviado que cumplió con los criterios de control de calidad

3 de enero de 2017

Publicado por primera vez (Estimar)

5 de enero de 2017

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

13 de agosto de 2019

Última actualización enviada que cumplió con los criterios de control de calidad

9 de agosto de 2019

Última verificación

1 de agosto de 2019

Más información

Términos relacionados con este estudio

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

NO

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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