- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT01716494
Washington University Severe Asthma Research Program III (WU SARPIII)
5 oktober 2020 uppdaterad av: Washington University School of Medicine
Severe Asthma Research Program (SARP)-Washington University
The overall goal of this proposal is to better understand the basis of airway remodeling in severe asthma and how remodeling changes over time.
The investigators propose to study a well-characterized cohort of adult and pediatric subjects with severe asthma using a multidisciplinary state-of-the-art approach.
Studieöversikt
Status
Okänd
Betingelser
Detaljerad beskrivning
The overall goal of this proposal is to better understand the molecular basis and structural and physiologic consequences of airway remodeling in severe asthma and how remodeling changes over time.
In that context, the investigators propose to study a well-characterized cohort of adult and pediatric subjects with severe asthma using a multidisciplinary approach that includes state-of-the-art morphometric, imaging, and physiologic measurements of airways.
The investigators will contrast these findings to those in groups with well-controlled asthma, normal controls, and diseased controls (chronic bronchitis) to identify features that can provide biologic targets unique to severe asthma.
The investigators have demonstrated that epithelial hyperplasia, goblet cell metaplasia and mucin production are features of airway remodeling in subjects with severe asthma, and that epithelial remodeling was due to increased epithelial proliferation and decreased cell death.
The investigators propose that individuals with severe asthma, in comparison to well controlled asthma, have: (I) increased airway remodeling as evidenced by goblet cell metaplasia and mucin production, (II) greater airway thickness by multidetector-row CT of the chest (MDCT) leading to ventilation defects demonstrated by hyperpolarized helium (3He) MRI and air trapping demonstrated by MDCT, and (III) airway remodeling associated with more severe and progressive airflow obstruction.
The investigators hypothesize that the goblet cell metaplasia and increased mucin The investigators have observed in severe asthma are being driven by an IL-13- and EGFR-dependent mechanism that inhibits epithelial cell apoptosis and allows IL-13 differentiation of the airway epithelium into goblet cells (Aim I).
The investigators further hypothesize that this remodeling of segmental airways in severe asthma leads to distal ventilation defects and air trapping (Aim II).
In an effort to define potential predictors of subsequent decline in lung function in severe asthma, the investigators hypothesize that baseline airway remodeling as reflected by MDCT airway wall area (AWA%) is predictive of FEV1 (post-corticosteroid/bronchodilator FEV1) decline (Aim III).
The identification of potential variables associated with remodeling and severe asthma will help identify individuals at risk whom would benefit from specific targeted therapy.
The concerted efforts of this project together with the SARP will lead to new insights on the mechanistic basis for severe asthma, further elucidate how it differs from mild-moderate asthma, identify potential targets for intervention, and will provide imaging metrics to objectively evaluate outcomes for new treatments.
Studietyp
Observationell
Inskrivning (Faktisk)
121
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
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Missouri
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Saint Louis, Missouri, Förenta staterna, 63110
- Washington University School of Medicine
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
6 år och äldre (Barn, Vuxen, Äldre vuxen)
Tar emot friska volontärer
Ja
Kön som är behöriga för studier
Allt
Testmetod
Icke-sannolikhetsprov
Studera befolkning
Subjects with asthma (severe asthma, well controlled asthma) and healthy normal controls from St. Louis region
Beskrivning
Inclusion Criteria:
- Physician diagnosis of asthma,
- Age 6 years and older
Evidence of historical reversibility, including either:
- FEV1 bronchodilator reversibility ≥ 12%, or
- Airway hyperresponsiveness reflected by a methacholine PC20 ≤16 mg/mL.
Exclusion Criteria:
- No primary medical caregiver,
- Pregnancy (if undergoing methacholine challenge or bronchoscopy),
- Current smoking
- Smoking history > 10 pack years if ≥ 30 years of age or smoking history > 5 pack years if < 30 years of age (Note: If a subject has a smoking history, no smoking within the past year)
- Other chronic pulmonary disorders associated with asthma-like symptoms,including (but not limited to) cystic fibrosis, chronic obstructive pulmonary disease, chronic bronchitis, vocal cord dysfunction that is the sole cause of asthma symptoms, severe scoliosis or chest wall deformities that affect lung function, or congenital disorders of the lungs or airways,
- History of premature birth before 35 weeks gestation,
- Evidence that the participant or family may be unreliable or poorly adherent to their asthma treatment or study procedures,
- Planning to relocate from the clinical center area before study completion, or
- Any other criteria that place the subject at unnecessary risk according to the judgment of the Principal Investigator and/or attending physician(s) of record.
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
Kohorter och interventioner
Grupp / Kohort |
---|
Välkontrollerad astma
Försökspersoner med välkontrollerad astma
|
Normal kontroll
Ämnen som är friska normala
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Severe Asthma
Subjects with severe asthma (SARP protocol definition)
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Lung function
Tidsram: 3 yrs
|
decline in lung function (FEV1) over 3 yrs
|
3 yrs
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Asthma Control Questionnaire
Tidsram: 3 yrs
|
asthma control score (ACQ)
|
3 yrs
|
Health care utilization
Tidsram: 3 yrs
|
Health care utilization including ED visits and hospitalizations.
|
3 yrs
|
Exacerbation
Tidsram: 3 yrs
|
Exacerbations requiring systemic steroids
|
3 yrs
|
CT quantification
Tidsram: 3 yrs
|
CT airway wall thickness, lung density
|
3 yrs
|
MRI
Tidsram: 3 yrs
|
Ventilation defects on hyperpolarized gas MRI
|
3 yrs
|
Morphometric biopsy
Tidsram: 3 yrs
|
Morphometric analysis of airway biopsies
|
3 yrs
|
Gene expression
Tidsram: 3 yrs
|
Gene expression studies of airway epithelial cells
|
3 yrs
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Utredare
- Huvudutredare: Kaharu Sumino, MD, Washington University School of Medicine
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- Dunican EM, Elicker BM, Gierada DS, Nagle SK, Schiebler ML, Newell JD, Raymond WW, Lachowicz-Scroggins ME, Di Maio S, Hoffman EA, Castro M, Fain SB, Jarjour NN, Israel E, Levy BD, Erzurum SC, Wenzel SE, Meyers DA, Bleecker ER, Phillips BR, Mauger DT, Gordon ED, Woodruff PG, Peters MC, Fahy JV; National Heart Lung and Blood Institute (NHLBI) Severe Asthma Research Program (SARP). Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction. J Clin Invest. 2018 Mar 1;128(3):997-1009. doi: 10.1172/JCI95693. Epub 2018 Feb 5.
- Witt CA, Sheshadri A, Carlstrom L, Tarsi J, Kozlowski J, Wilson B, Gierada DS, Hoffman E, Fain SB, Cook-Granroth J, Sajol G, Sierra O, Giri T, O'Neill M, Zheng J, Schechtman KB, Bacharier LB, Jarjour N, Busse W, Castro M; NHLBI Severe Asthma Research Program (SARP). Longitudinal changes in airway remodeling and air trapping in severe asthma. Acad Radiol. 2014 Aug;21(8):986-93. doi: 10.1016/j.acra.2014.05.001.
Användbara länkar
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
1 oktober 2012
Primärt slutförande (Förväntat)
1 mars 2021
Avslutad studie (Förväntat)
1 mars 2021
Studieregistreringsdatum
Först inskickad
25 oktober 2012
Först inskickad som uppfyllde QC-kriterierna
26 oktober 2012
Första postat (Uppskatta)
29 oktober 2012
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
6 oktober 2020
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
5 oktober 2020
Senast verifierad
1 oktober 2020
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- 201206102
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