- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01898767
Eicosanoid Lipids by Airway Cells During Infection With Human Rhinoviruses
27. marts 2019 opdateret af: University of Wisconsin, Madison
Production of Eicosanoid Lipids by Airway Cells During Infection With Human Rhinoviruses: An In Vitro Model System to Study the Mechanisms of Asthma Exacerbation Resolution
The long-range goal of this protocol is to more completely understand the risks and the pathophysiology of asthma exacerbations, in order to develop prevention strategies and/or expedite a return to complete control of baseline asthma symptoms.
Studieoversigt
Status
Afsluttet
Betingelser
Detaljeret beskrivelse
Theinvestigators and others have shown that airway epithelial cell infection with human rhinovirus (HRV) is a major risk factor for subsequent exacerbation.
Additionally, the investigators have shown that the nucleotide receptor, P2X7, is an important host factor in the prevention of exacerbations, and have data to suggest that this may occur at the level of the alveolar macrophage.
Alveolar macrophages facilitate the resolution of inflammation in part by generating eicosanoid metabolites of arachidonic acid including prostaglandin E2 (PGE2) and lipoxin A4 (LXA4).
Patients with severe asthma have a reduced capacity to generate PGE2 and LXA4 when compared to those with non-severe asthma, despite alveolar macrophage expression of two of the key enzymes involved in their production.
These and other data suggest that pro-resolving eicosanoid metabolism is most efficient when airway epithelial cells are in communication with alveolar macrophages, and that these pathways may be defective in patients with severe asthma.
Moreover, inoculation experiments with human rhinovirus (HRV) demonstrate that alveolar macrophages express cox-2 during resolution.
These and other data have led to the central hypothesis that transcellular generation of PGE2 and lipoxins is regulated by P2X7-induced cox-2 expression in alveolar macrophages, and that this process facilitates resolution of an HRV-triggered exacerbation.
Undersøgelsestype
Observationel
Tilmelding (Faktiske)
44
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
Wisconsin
-
Madison, Wisconsin, Forenede Stater, 53792
- UW Madison
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 55 år (Voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Prøveudtagningsmetode
Ikke-sandsynlighedsprøve
Studiebefolkning
Subjects with mild asthma from Madison, WI region
Beskrivelse
Inclusion Criteria:
- Age 18-55 years
- Diagnosis of mild asthma
- Pre-albuterol forced expiratory volume in the first second (FEV1) of >70% predicted.
- Confirmation of asthma diagnosis by either an improvement in FEV1 after four puffs of albuterol by ≥ 12%, or a decline in FEV1 by ≥ 20% after a graded challenge with inhaled methacholine with a provocative concentration causing a 20% fall ≤ 8 mg/mL
- Documented negative Tuberculin skin test (PPD) within the last 12 months or a medical history that is consistent with a low probability of exposure to tuberculosis (i.e. the subject is not a health worker, has not traveled to endemic areas, and has no pre-existing medical or social risk factors for tuberculosis).
- Safety laboratory assessments within normal ranges (labs to include complete blood count with differential and platelet count, PT/INR, creatinine, ALT)
- Women of child-bearing potential (WCBP) must have a negative urine pregnancy test (urine HCG) within 48 hours of the methacholine challenge at Visit 2, within 48 hours of the bronchoscopy at Visit 3 and within 48 hrs of Visit 4. WCBP must agree to use a reliable method of birth control for the duration of the study (reliable methods of birth control can include abstinence, barrier methods, oral contraceptives, injection contraceptives or skin absorption contraceptives).
- In the opinion of the investigator, capable and willing to grant written informed consent and cooperate with study procedures and requirements.
Exclusion Criteria:
- Major health problems such as autoimmune disease, heart disease, type I and II diabetes, uncontrolled hypertension or lung diseases other than asthma. The listed health problems are definitive exclusion but decisions regarding major health problems not listed will be based upon the judgment of the investigator.
- No pre-existing chronic infectious disease.
- Any condition for which, in the opinion of the investigator, transient oxyhemoglobin desaturation is inadvisable.
- Pregnant or lactating females or has a planned pregnancy during the course of the study.
- Asthma maintenance therapy other than inhaled short acting beta-agonists within 1 month of screening. This includes but is not limited to inhaled or oral corticosteroids, long acting beta-agonists and leukotriene receptor antagonists.
- Upper or lower respiratory infection within 1 month of screening.
- Unstable asthma as indicated by self-report of increased symptoms or increased beta-agonist use over the 2 weeks preceding the screening visit.
- Current smokers (defined as smoked within the last year) or a former smoker with a history of >10 pack years.
- Morbid obesity as defined by a Body Mass Index (BMI) > 40.
- Use of an investigational drug within 30 days of entering the study
- History of noncompliance with medical regiments or subjects who are considered unreliable including those with a psychiatric history that, in the opinion of the investigator, may interfere with the conduct of study procedures.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Kohorter og interventioner
Gruppe / kohorte |
---|
Mild asthma
Diagnosis of mild asthma as defined by pre-albuterol forced expiratory volume in the first second (FEV1) of >70% predicted.
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Cox2 expression
Tidsramme: One day
|
P2X7 agonist-induced fold stimulation (over the media control) of cox2 expression (assessed by densitometry) in alveolar macrophages primed with conditioned medium from minor group HRV-infected epithelial cells.
|
One day
|
BzATP-induced PGE2
Tidsramme: One day
|
The amount of BzATP-induced PGE2 in the culture supernatants of alveolar macrophages primed with HRV-infected epithelial conditioned media
|
One day
|
LXA4 produced by BzATP
Tidsramme: One day
|
The amount of LXA4 produced by BzATP co-treatment of HRV infected of epithelial-macrophage co-cultures.
|
One day
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Loren Denlinger, MD/PhD, UW Madison
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
17. december 2013
Primær færdiggørelse (Faktiske)
29. august 2017
Studieafslutning (Faktiske)
29. august 2017
Datoer for studieregistrering
Først indsendt
9. juli 2013
Først indsendt, der opfyldte QC-kriterier
11. juli 2013
Først opslået (Skøn)
12. juli 2013
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
28. marts 2019
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
27. marts 2019
Sidst verificeret
1. marts 2019
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 2013-0935
- 1R01HL115118-01A1 (U.S. NIH-bevilling/kontrakt)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
JA
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .