AsthmaNCT01760915
University of Wisconsin Severe Asthma Research Program III
An observational study of Asthma, run by University of Wisconsin, Madison at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 years and olderHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- NC100182 Hyperpolarized 3He
- How many people
- 107 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Nov 2012to 17 Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Subjects with asthma (severe asthma, well controlled asthma) and healthy normal controls from Madison, WI region
Who may be able to join
- 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.
Who cannot join
- 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,
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Severe Asthma Research Program (SARP) - University of Wisconsin
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.
Read the 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.
- Conditions
- Asthma
- Being tested
- NC100182 Hyperpolarized 3He
- Keywords
- asthma, severe
- Medical subject headings
- Asthma, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NC100182 Hyperpolarized 3HeOther
Also called helium
Magnetic Resonance Imaging (MRI) will take place and include inhalation of hyperpolarized helium to construct an image of the lungs.
| Study group | Role | What they receive |
|---|---|---|
| Severe asthma | Subjects with severe asthma (SARP protocol definition) Receives: Other: NC100182 Hyperpolarized 3He | |
| Well controlled asthma | Subjects with well controlled asthma Receives: Other: NC100182 Hyperpolarized 3He | |
| Normal control | Subjects that are healthy normals Receives: Other: NC100182 Hyperpolarized 3He |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lung function
Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by lung function.
Measured: Baseline versus 3 years
Secondary outcomes (8)
Plethysmographic lung volumes
Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by Plethysmographic lung volumes.
Measured: Baseline versus 3 years
Hyperpolarized gas magnetic resonance imaging
Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by Hyperpolarized gas magnetic resonance imaging.
Measured: Baseline versus 3 years
Multidetector computed tomography imaging
Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by Multidetector computed tomography imaging (adults only).
Measured: Baseline versus 3 years
Exacerbations
Exacerbation requiring systemic steroids
Measured: Baseline versus 3 years
Plasma levels of biomarkers
Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by plasma levels of biomarkers.
Measured: Baseline versus 3 years
Induced sputum mediators
Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by induced sputum mediators.
Measured: Baseline versus 3 years
Nasal washing samples for virology
Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by nasal washing samples for virology.
Measured: Baseline versus 3 years
Bronchoscopy samples for virology, inflammatory cells and mediators
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).
Measured: Baseline versus 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2013 (estimated)
- Study start28 Nov 2012
- Primary completion24 Mar 2020
- Study completion17 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Washington University School of Medicine, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Nizar N Jarjour, MD, Principal investigator, UW Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01760915
- Sponsor's protocol ID
- 2012-0571
- Other IDs
- 4U10HL109168, A534285, R01HL115118, MRTG-02-15-2022
- Status last verified
- Jul 2023
- First submitted
- 26 Dec 2012
- Last updated
- 2 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Huang BK, Elicker BM, Henry TS, Kallianos KG, Hahn LD, Tang M, Heng F, McCulloch CE, Bhakta NR, Majumdar S, Choi J, Denlinger LC, Fain SB, Hastie AT, Hoffman EA, Israel E, Jarjour NN, Levy BD, Mauger DT, Sumino K, Wenzel SE, Castro M, Woodruff PG, Fahy JV, Sarp FTNSARP. Persistent mucus plugs in proximal airways are consequential for airflow limitation in asthma. JCI Insight. 2024 Feb 8;9(3):e174124. doi: 10.1172/jci.insight.174124.
PubMed 38127464Dunican 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.
PubMed 29400693Denlinger LC, Phillips BR, Ramratnam S, Ross K, Bhakta NR, Cardet JC, Castro M, Peters SP, Phipatanakul W, Aujla S, Bacharier LB, Bleecker ER, Comhair SA, Coverstone A, DeBoer M, Erzurum SC, Fain SB, Fajt M, Fitzpatrick AM, Gaffin J, Gaston B, Hastie AT, Hawkins GA, Holguin F, Irani AM, Israel E, Levy BD, Ly N, Meyers DA, Moore WC, Myers R, Opina MT, Peters MC, Schiebler ML, Sorkness RL, Teague WG, Wenzel SE, Woodruff PG, Mauger DT, Fahy JV, Jarjour NN; National Heart, Lung, and Blood Institute's Severe Asthma Research Program-3 Investigators. Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations. Am J Respir Crit Care Med. 2017 Feb 1;195(3):302-313. doi: 10.1164/rccm.201602-0419OC.
PubMed 27556234Witt 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.
PubMed 25018070
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Severe Asthma Research Program (SARP) - University of Wisconsin
- ClinicalTrials.gov ID
- NCT01760915
- Acronym / sponsor ID
- 2012-0571
- Conditions
- Asthma
- Keywords
- asthma, severe
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Washington University School of Medicine, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 28 Nov 2012 (actual)
- Primary completion
- 24 Mar 2020 (actual)
- Study completion
- 17 Dec 2021 (actual)
- First posted
- 4 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Severe asthma | – | Other: NC100182 Hyperpolarized 3HeSubjects with severe asthma (SARP protocol definition) |
| Well controlled asthma | – | Other: NC100182 Hyperpolarized 3HeSubjects with well controlled asthma |
| Normal control | – | Other: NC100182 Hyperpolarized 3HeSubjects that are healthy normals |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Subjects with asthma (severe asthma, well controlled asthma) and healthy normal controls from Madison, WI region
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NC100182 Hyperpolarized 3HeAlso: heliumMagnetic Resonance Imaging (MRI) will take place and include inhalation of hyperpolarized helium to construct an image of the lungs. | Other | Normal control, Severe asthma, Well controlled asthma |
Primary outcome
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.
8 secondary outcomes
Plethysmographic lung volumes
Time frame: Baseline versus 3 years
Hyperpolarized gas magnetic resonance imaging
Time frame: Baseline versus 3 years
Multidetector computed tomography imaging
Time frame: Baseline versus 3 years
Exacerbations
Time frame: Baseline versus 3 years
Plasma levels of biomarkers
Time frame: Baseline versus 3 years
Induced sputum mediators
Time frame: Baseline versus 3 years
Nasal washing samples for virology
Time frame: Baseline versus 3 years
Bronchoscopy samples for virology, inflammatory cells and mediators
Time frame: Baseline versus 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2023.
- Derived from this study: PubMed 38127464Huang BK, Elicker BM, Henry TS, Kallianos KG, Hahn LD, Tang M, Heng F, McCulloch CE, Bhakta NR, Majumdar S, Choi J, Denlinger LC, Fain SB, Hastie AT, Hoffman EA, Israel E, Jarjour NN, Levy BD, Mauger DT, Sumino K, Wenzel SE, Castro M, Woodruff PG, Fahy JV, Sarp FTNSARP. Persistent mucus plugs in proximal airways are consequential for airflow limitation in asthma. JCI Insight. 2024 Feb 8;9(3):e174124. doi: 10.1172/jci.insight.174124.
- Derived from this study: PubMed 29400693Dunican 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.
- Derived from this study: PubMed 27556234Denlinger LC, Phillips BR, Ramratnam S, Ross K, Bhakta NR, Cardet JC, Castro M, Peters SP, Phipatanakul W, Aujla S, Bacharier LB, Bleecker ER, Comhair SA, Coverstone A, DeBoer M, Erzurum SC, Fain SB, Fajt M, Fitzpatrick AM, Gaffin J, Gaston B, Hastie AT, Hawkins GA, Holguin F, Irani AM, Israel E, Levy BD, Ly N, Meyers DA, Moore WC, Myers R, Opina MT, Peters MC, Schiebler ML, Sorkness RL, Teague WG, Wenzel SE, Woodruff PG, Mauger DT, Fahy JV, Jarjour NN; National Heart, Lung, and Blood Institute's Severe Asthma Research Program-3 Investigators. Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations. Am J Respir Crit Care Med. 2017 Feb 1;195(3):302-313. doi: 10.1164/rccm.201602-0419OC.
- Derived from this study: PubMed 25018070Witt 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.
- SARP WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nizar N Jarjour, MD principal investigator
UW Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Asthma, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lung function (time frame: Baseline versus 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01760915, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2023.