- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00595153
Study of the Mechanisms of Asthma (MAST)
5. desember 2013 oppdatert av: University of California, San Francisco
Determining Mechanisms of Asthma Through Detailed Analysis of Airway Secretions and Tissues
The purpose of this study is to identify the causes of asthma that were not previously suspected, to better understand the effects of inhaled steroids on asthma and to identify new way to treat asthma.
In order to take advantage of the most current scientific expertise, we (scientists at UCSF) plan to work together with Genentech Inc.
We believe that working with Genentech will provide the best chance of developing new treatments for asthma.
Studieoversikt
Detaljert beskrivelse
Asthma is a common airway disease with persistent unmet needs on terms of treatment.
Although many asthmatics enjoy good control of their disease by using regularly scheduled corticosteroid treatment, a significant minority do not achieve optimal control with steroids and suffer asthma exacerbations which can be severe and even fatal.
Asthma pathophysiology is complex and involves multiple cell types and multiple signaling mechanisms.
One approach to this complexity has been to study responses of isolated airway cells to experimental conditions which model asthmatic inflammation; another has been genetic manipulations of candidate mediators of asthma in inbred mice.
These studies have yielded important insights about possible mechanisms of asthma in humans, but the relevance of these mechanisms to human disease has not always been proven, and it is possible that unsuspected mechanism have not yet been revealed by these approaches.
In the studies proposed here we will take an experimental approach which takes advantage of the distinct clinical phenotype of human asthma, the ability to measure steroid response in asthma, the relative ease of collecting airway cells and tissues by bronchoscopy, and the availability of new technologies such as high density microarrays which have probes for all genes in the genome or proteomics which can identify all proteins present in a biologic sample.
Using this approach, we will identify differential expression of genes and proteins in airway cells and tissues in asthma that can then be explored further in cell and animal model systems to determine their potential as drug targets in asthma.
We further believe that our approach will identify previously unsuspected mechanisms of action of corticosteroids in airway cells and tissues in asthma.
Presently, relatively little is known about why some asthmatics respond well and some poorly to steroids and closing this gap in knowledge will help identify candidate genes and proteins to target in order to address unmet therapeutic needs in asthmatics with steroid resistant asthma.
Studietype
Intervensjonell
Registrering (Faktiske)
127
Fase
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
-
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California
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San Francisco, California, Forente stater, 94143
- University of California, San Francisco
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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 til 70 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Ja
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
Group C:
- Male and female subjects between the ages of 18 and 70 years
- History of asthma
- Continuous treatment with inhaled corticosteroids for at least the 6-week
- Hyperreactivity to methacholine (provocative concentration of methacholine causing a 20% drop in forced expiratory volume in 1 second (PC20 FEV1) Methacholine ≤ 16.0 mg/mL).
Exclusion Criteria:
- History of asthma
- No use of oral or inhaled corticosteroids for the treatment of asthma in the past 6 weeks
- Hyperreactivity to methacholine (PC20 FEV1 Methacholine ≤ 8.0 mg/mL).
At least one of the following symptoms, beta agonist use, or FEV1 criteria:
- Asthma symptoms on at least two days per week; OR
- Beta agonist use on at least two days per week; OR
- Forced expiratory volume in 1 second (FEV1) < 85% predicted
- Subjects must be non-smokers (patients who have never smoked or patients who have not smoked for 1 year and have a total pack-year smoking history < 15 packs).
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Grunnvitenskap
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Aktiv komparator: B
Asthmatics not on inhaled corticosteroids who will be put on an inhaled steroid during the study
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inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks
Andre navn:
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Ingen inngripen: A
Healthy, non-asthmatics who will not be put on any intervention
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Aktiv komparator: C
Asthmatics, who are already on inhaled corticosteroids who will be put on standardized dose of inhaled corticosteroids
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inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Gene Expression in Airway Secretions and Tissues
Tidsramme: Healthy Control: Visit 2 (at 1 week); Steroid Naive Asthmatics: Visit 2 (at 1 week); Steroid Treated Asthmatics: Visit 5 (at 9 weeks)
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The primary outcome measure for this study is the scaled mean value of three gene expression markers of IL-13 in the airway: PERIOSTIN, calcium-activated chloride channel regulator 1 (CLCA1), and plasminogen activator inhibitor-2 (SERPINB2).
First, for each of the three interleukin-13 (IL-13) signature genes, the log (base-2) transformed relative expression value for each subject is measured using real-time polymerase chair reaction (PCR) and normalized with the geometric mean of 5 housekeeping genes.
Next, these values are centered (by subtracting the mean for that gene) and scaled (by dividing by the standard deviation for that gene) so that each gene makes an equal, assay-independent contribution to the Th2 phenotype.
Then, for each subject, the arithmetic mean of the three centered & scaled genes is calculated, producing the "three-gene-mean" metric.
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Healthy Control: Visit 2 (at 1 week); Steroid Naive Asthmatics: Visit 2 (at 1 week); Steroid Treated Asthmatics: Visit 5 (at 9 weeks)
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: John V Fahy, M.D., M.Sc., University of California, San Francisco
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Hjelpsomme linker
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
1. april 2007
Primær fullføring (Faktiske)
1. juni 2011
Studiet fullført (Faktiske)
1. juni 2011
Datoer for studieregistrering
Først innsendt
2. januar 2008
Først innsendt som oppfylte QC-kriteriene
15. januar 2008
Først lagt ut (Anslag)
16. januar 2008
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
20. januar 2014
Siste oppdatering sendt inn som oppfylte QC-kriteriene
5. desember 2013
Sist bekreftet
1. desember 2013
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Sykdommer i luftveiene
- Sykdommer i immunsystemet
- Lungesykdommer
- Overfølsomhet, Umiddelbar
- Bronkiale sykdommer
- Lungesykdommer, obstruktiv
- Respiratorisk overfølsomhet
- Overfølsomhet
- Astma
- Fysiologiske effekter av legemidler
- Autonome agenter
- Agenter fra det perifere nervesystemet
- Anti-inflammatoriske midler
- Glukokortikoider
- Hormoner
- Hormoner, hormonsubstitutter og hormonantagonister
- Bronkodilatatorer
- Anti-astmatiske midler
- Luftveismidler
- Budesonid
Andre studie-ID-numre
- UCSF CHR# H6788-30617
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
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