We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu

Washington University Severe Asthma Research Program III (WU SARPIII)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01716494
Recruitment Status : Active, not recruiting
First Posted : October 29, 2012
Last Update Posted : June 26, 2017
Information provided by (Responsible Party):
Mario Castro, Washington University School of Medicine

Brief Summary:
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.

Condition or disease

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
Actual Enrollment : 121 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Severe Asthma Research Program (SARP)-Washington University
Actual Study Start Date : October 2012
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
U.S. FDA Resources

Severe Asthma
Subjects with severe asthma (SARP protocol definition)
Well controlled asthma
Subjects with well controlled asthma
Normal control
Subjects that are healthy normals

Primary Outcome Measures :
  1. Lung function [ Time Frame: 3 yrs ]
    decline in lung function (FEV1) over 3 yrs

Secondary Outcome Measures :
  1. Asthma Control Questionnaire [ Time Frame: 3 yrs ]
    asthma control score (ACQ)

  2. Health care utilization [ Time Frame: 3 yrs ]
    Health care utilization including ED visits and hospitalizations.

  3. Exacerbation [ Time Frame: 3 yrs ]
    Exacerbations requiring systemic steroids

  4. CT quantification [ Time Frame: 3 yrs ]
    CT airway wall thickness, lung density

  5. MRI [ Time Frame: 3 yrs ]
    Ventilation defects on hyperpolarized gas MRI

  6. Morphometric biopsy [ Time Frame: 3 yrs ]
    Morphometric analysis of airway biopsies

  7. Gene expression [ Time Frame: 3 yrs ]
    Gene expression studies of airway epithelial cells

Biospecimen Retention:   Samples With DNA
whole blood, serum, plasma, DNA, RNA, sputum, urine, bronchial tissue, bronchoalveolar lavage, bronchial brushings, exhaled breath condensate

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   6 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Subjects with asthma (severe asthma, well controlled asthma) and healthy normal controls from St. Louis region

Inclusion Criteria:

  1. Physician diagnosis of asthma,
  2. Age 6 years and older
  3. Evidence of historical reversibility, including either:

    1. FEV1 bronchodilator reversibility ≥ 12%, or
    2. Airway hyperresponsiveness reflected by a methacholine PC20 ≤16 mg/mL.

Exclusion Criteria:

  1. No primary medical caregiver,
  2. Pregnancy (if undergoing methacholine challenge or bronchoscopy),
  3. Current smoking
  4. 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)
  5. 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,
  6. History of premature birth before 35 weeks gestation,
  7. Evidence that the participant or family may be unreliable or poorly adherent to their asthma treatment or study procedures,
  8. Planning to relocate from the clinical center area before study completion, or
  9. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01716494

United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Principal Investigator: Mario Castro, MD, MPH Washington University School of Medicine

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mario Castro, Professor of Medicine and Pediatrics, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01716494     History of Changes
Other Study ID Numbers: 201206102
First Posted: October 29, 2012    Key Record Dates
Last Update Posted: June 26, 2017
Last Verified: June 2017

Keywords provided by Mario Castro, Washington University School of Medicine:

Additional relevant MeSH terms:
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases