Washington University Severe Asthma Research Program III (WU SARPIII)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Mario Castro, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01716494
First received: October 25, 2012
Last updated: October 26, 2012
Last verified: October 2012
  Purpose

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
Asthma

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Severe Asthma Research Program (SARP)-Washington University

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Lung function [ Time Frame: 3 yrs ] [ Designated as safety issue: No ]
    decline in lung function (FEV1) over 3 yrs


Secondary Outcome Measures:
  • Asthma Control Questionnaire [ Time Frame: 3 yrs ] [ Designated as safety issue: No ]
    asthma control score (ACQ)

  • Health care utilization [ Time Frame: 3 yrs ] [ Designated as safety issue: No ]
    Health care utilization including ED visits and hospitalizations.

  • Exacerbation [ Time Frame: 3 yrs ] [ Designated as safety issue: No ]
    Exacerbations requiring systemic steroids

  • CT quantification [ Time Frame: 3 yrs ] [ Designated as safety issue: No ]
    CT airway wall thickness, lung density

  • MRI [ Time Frame: 3 yrs ] [ Designated as safety issue: No ]
    Ventilation defects on hyperpolarized gas MRI

  • Morphometric biopsy [ Time Frame: 3 yrs ] [ Designated as safety issue: No ]
    Morphometric analysis of airway biopsies

  • Gene expression [ Time Frame: 3 yrs ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 130
Study Start Date: October 2012
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
Severe Asthma
Subjects with severe asthma (SARP protocol definition)
Well controlled asthma
Subjects with well controlled asthma
Normal control
Subjects that are healthy normals

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.

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
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

Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01716494

Contacts
Contact: Becky K Schutz, RN, BSN 314-362-8892 rschutz@dom.wustl.edu
Contact: Tammy Koch, RN 314-747-3063 tkoch@dom.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Sub-Investigator: Adrian Shifren, MD         
Sub-Investigator: Kaharu Sumino, MD         
Sub-Investigator: Leonard Bacharier, MD         
Sub-Investigator: David Gierada, MD         
Sub-Investigator: Ken Schechtman, PhD         
Sub-Investigator: Jason Woods, PhD         
Sub-Investigator: Anand Patel, MD         
Sub-Investigator: James Quirk, PhD         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Mario Castro, MD, MPH Washington University School of Medicine
  More Information

Additional Information:
No publications provided by Washington University School of Medicine

Additional 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
Study First Received: October 25, 2012
Last Updated: October 26, 2012
Health Authority: United States: National Institutes of Health

Keywords provided by Washington University School of Medicine:
asthma

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

ClinicalTrials.gov processed this record on September 14, 2014