University of Wisconsin Severe Asthma Research Program III

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of Wisconsin, Madison
Sponsor:
Collaborators:
Washington University School of Medicine
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT01760915
First received: December 26, 2012
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

The overall goal of this proposal is to better understand the basis of structural airway changes in severe asthma and how asthma exacerbations may contribute to their progression over time. The investigators propose to study a well-characterized cohort of adult and pediatric subjects with asthma using a multidisciplinary state-of-the-art approach. We hypothesize that severe asthma exacerbations, in some patients, are associated with incomplete recovery and activation of airway inflammatory cells in a regional distribution. The end result is a more permanent and less reversible airway obstruction that is a prominent feature of severe asthma.


Condition
Asthma

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

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Lung function [ Time Frame: Baseline versus 3 years ] [ Designated as safety issue: No ]
    Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by lung function.


Secondary Outcome Measures:
  • Plethysmographic lung volumes [ Time Frame: Baseline versus 3 years ] [ Designated as safety issue: No ]
    Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by Plethysmographic lung volumes.

  • Hyperpolarized gas magnetic resonance imaging [ Time Frame: Baseline versus 3 years ] [ Designated as safety issue: No ]
    Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by Hyperpolarized gas magnetic resonance imaging.

  • Multidetector computed tomography imaging [ Time Frame: Baseline versus 3 years ] [ Designated as safety issue: No ]
    Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by Multidetector computed tomography imaging (adults only).

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

  • Plasma levels of biomarkers [ Time Frame: Baseline versus 3 years ] [ Designated as safety issue: No ]
    Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by plasma levels of biomarkers.

  • Induced sputum mediators [ Time Frame: Baseline versus 3 years ] [ Designated as safety issue: No ]
    Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by induced sputum mediators.

  • Nasal washing samples for virology [ Time Frame: Baseline versus 3 years ] [ Designated as safety issue: No ]
    Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by nasal washing samples for virology.

  • Bronchoscopy samples for virology, inflammatory cells and mediators [ Time Frame: Baseline versus 3 years ] [ Designated as safety issue: No ]
    Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by bronchoscopy samples for virology, inflammatory cells and mediators (adults only).


Biospecimen Retention:   Samples With DNA

whole blood, serum, plasma, DNA, RNA, sputum, urine, bronchial tissue, bronchoalveolar lavage, bronchial brushings, exhaled breath condensate


Estimated Enrollment: 120
Study Start Date: December 2012
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 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:

We have shown that patients with severe asthma have heterogeneous regional ventilation defects and air trapping. Some of these defects are persistent, while others can be provoked with virus-induced exacerbations or bronchial challenge and recur in the same general areas on repeated challenge, suggesting localized airway dysfunction. In preliminary studies, inflammatory parameters tended to be more prominent in segments that showed ventilation defects on imaging. Therefore, we hypothesize that asthma exacerbations, in some patients, are associated with incomplete recovery and activation of airway inflammatory cells in a regional distribution. This leads to enhanced airway injury with airway dysfunction as reflected by ventilation defects and air trapping, and a more generalized increase in disease severity. To evaluate this hypothesis we propose the following specific aims: 1. To refine phenotyping of severe asthma using new variables from multiple domains in a large longitudinal patient cohort; and to determine the contribution of asthma exacerbations to disease progression. 2. To characterize regional obstructive patterns at baseline and their relationship to changes in pulmonary function; and to determine how incremental changes in regional airway dysfunction after asthma exacerbations may contribute to severe asthma. 3. To determine the contribution of established and novel biomarkers (YKL-40, vWF, & P-selectin), in refining the severe asthma phenotypes and the role of inflammatory cells in causing airway injury following virus-induced asthma exacerbations with subsequent development of ventilation defects.

  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 Madison, WI 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: NCT01760915

Contacts
Contact: Michele Wolff, RN 608-263-0524 mjwolff@medicine.wisc.edu
Contact: Gina Crisafi, BS 608-265-4554 gmc@medicine.wisc.edu

Locations
United States, Wisconsin
UW Madison Recruiting
Madison, Wisconsin, United States, 53792
Contact: Michele Wolff, RN    608-263-0524    mjwolff@medicine.wisc.edu   
Contact: Gina Crisafi, BS    608-265-4554    gmc@medicine.wisc.edu   
Principal Investigator: Nizar N Jarjour, MD         
Sub-Investigator: Loren Denlinger, MD, PhD         
Sub-Investigator: Sean Fain, PhD         
Sub-Investigator: Ronald Sorkness, PhD         
Sub-Investigator: Theresa Guilbert, MD         
Sub-Investigator: Elizabeth Kelly, PhD         
Sponsors and Collaborators
University of Wisconsin, Madison
Washington University School of Medicine
Investigators
Principal Investigator: Nizar N Jarjour, MD UW Madison
  More Information

Additional Information:
No publications provided by University of Wisconsin, Madison

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT01760915     History of Changes
Other Study ID Numbers: 2012-0571
Study First Received: December 26, 2012
Last Updated: February 11, 2014
Health Authority: United States: National Institutes of Health Data and Safety Monitoring Board

Keywords provided by University of Wisconsin, Madison:
asthma
severe

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 22, 2014