University of Wisconsin Severe Asthma Research Program III
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| ClinicalTrials.gov Identifier: NCT01760915 |
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Recruitment Status :
Active, not recruiting
First Posted : January 4, 2013
Last Update Posted : January 9, 2019
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Sponsor:
University of Wisconsin, Madison
Collaborators:
National Institutes of Health (NIH)
Washington University School of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of Wisconsin, Madison
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Brief Summary:
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 or disease | Intervention/treatment |
|---|---|
| Asthma | Other: NC100182 Hyperpolarized 3He |
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.
| Study Type : | Observational |
| Estimated Enrollment : | 120 participants |
| Observational Model: | Cohort |
| Time Perspective: | Prospective |
| Official Title: | Severe Asthma Research Program (SARP) - University of Wisconsin |
| Study Start Date : | December 2012 |
| Estimated Primary Completion Date : | December 2019 |
| Estimated Study Completion Date : | December 2019 |
| Group/Cohort | Intervention/treatment |
|---|---|
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Severe asthma
Subjects with severe asthma (SARP protocol definition)
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Other: NC100182 Hyperpolarized 3He
Magnetic Resonance Imaging (MRI) will take place and include inhalation of hyperpolarized helium to construct an image of the lungs.
Other Name: helium |
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Well controlled asthma
Subjects with well controlled asthma
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Other: NC100182 Hyperpolarized 3He
Magnetic Resonance Imaging (MRI) will take place and include inhalation of hyperpolarized helium to construct an image of the lungs.
Other Name: helium |
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Normal control
Subjects that are healthy normals
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Other: NC100182 Hyperpolarized 3He
Magnetic Resonance Imaging (MRI) will take place and include inhalation of hyperpolarized helium to construct an image of the lungs.
Other Name: helium |
Primary Outcome Measures :
- Lung function [ Time Frame: Baseline versus 3 years ]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 ]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 ]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 ]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 ]Exacerbation requiring systemic steroids
- Plasma levels of biomarkers [ Time Frame: Baseline versus 3 years ]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 ]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 ]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 ]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
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| Ages Eligible for Study: | 6 Years and older (Child, Adult, Older Adult) |
| 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 Madison, WI region
Criteria
Inclusion Criteria:
- Physician diagnosis of asthma
- Age 6 years and older
- 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:
- 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.
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): NCT01760915
Locations
| United States, Wisconsin | |
| UW Madison | |
| Madison, Wisconsin, United States, 53792 | |
Sponsors and Collaborators
University of Wisconsin, Madison
National Institutes of Health (NIH)
Washington University School of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
| Principal Investigator: | Nizar N Jarjour, MD | UW Madison |
Additional Information:
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 4U10HL109168 ( U.S. NIH Grant/Contract ) |
| First Posted: | January 4, 2013 Key Record Dates |
| Last Update Posted: | January 9, 2019 |
| Last Verified: | January 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
Keywords provided by University of Wisconsin, Madison:
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asthma severe |
Additional relevant MeSH terms:
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Asthma Bronchial Diseases Respiratory Tract Diseases Lung Diseases, Obstructive Lung Diseases |
Respiratory Hypersensitivity Hypersensitivity, Immediate Hypersensitivity Immune System Diseases |