- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01716494
Washington University Severe Asthma Research Program III (WU SARPIII)
October 5, 2020 updated by: 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.
Study Overview
Status
Unknown
Conditions
Detailed Description
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.
Study Type
Observational
Enrollment (Actual)
121
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
6 years and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
Subjects with asthma (severe asthma, well controlled asthma) and healthy normal controls from St. Louis region
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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Well controlled asthma
Subjects with well controlled asthma
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Normal control
Subjects that are healthy normals
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Severe Asthma
Subjects with severe asthma (SARP protocol definition)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Lung function
Time Frame: 3 yrs
|
decline in lung function (FEV1) over 3 yrs
|
3 yrs
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Asthma Control Questionnaire
Time Frame: 3 yrs
|
asthma control score (ACQ)
|
3 yrs
|
Health care utilization
Time Frame: 3 yrs
|
Health care utilization including ED visits and hospitalizations.
|
3 yrs
|
Exacerbation
Time Frame: 3 yrs
|
Exacerbations requiring systemic steroids
|
3 yrs
|
CT quantification
Time Frame: 3 yrs
|
CT airway wall thickness, lung density
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3 yrs
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MRI
Time Frame: 3 yrs
|
Ventilation defects on hyperpolarized gas MRI
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3 yrs
|
Morphometric biopsy
Time Frame: 3 yrs
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Morphometric analysis of airway biopsies
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3 yrs
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Gene expression
Time Frame: 3 yrs
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Gene expression studies of airway epithelial cells
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3 yrs
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Kaharu Sumino, MD, Washington University School of Medicine
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 1, 2012
Primary Completion (Anticipated)
March 1, 2021
Study Completion (Anticipated)
March 1, 2021
Study Registration Dates
First Submitted
October 25, 2012
First Submitted That Met QC Criteria
October 26, 2012
First Posted (Estimate)
October 29, 2012
Study Record Updates
Last Update Posted (Actual)
October 6, 2020
Last Update Submitted That Met QC Criteria
October 5, 2020
Last Verified
October 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 201206102
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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