University of Wisconsin Severe Asthma Research Program III

NCT01760915 | Completed DMC

• 5 other identifiers: 2012-05714U10HL109168A534285R01HL115118MRTG-02-15-2022
• Study Type: observational
• Target: 107
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Keywords

asthma; severe

Outcome Measures

Primary Outcomes (1)

• Lung function

  Changes in airway function after a severe exacerbation, and longitudinally over 3 years, as measured by lung function.

  Baseline versus 3 years

Secondary Outcomes (8)

• Plethysmographic lung volumes

  Baseline versus 3 years

• Hyperpolarized gas magnetic resonance imaging

  Baseline versus 3 years

• Multidetector computed tomography imaging

  Baseline versus 3 years

• Exacerbations

  Baseline versus 3 years

• Plasma levels of biomarkers

  Baseline versus 3 years

Study Arms (3)

Severe asthma

Subjects with severe asthma (SARP protocol definition)

Other: NC100182 Hyperpolarized 3He

Well controlled asthma

Subjects with well controlled asthma

Other: NC100182 Hyperpolarized 3He

Normal control

Subjects that are healthy normals

Other: NC100182 Hyperpolarized 3He

Interventions

NC100182 Hyperpolarized 3He OTHER

Magnetic Resonance Imaging (MRI) will take place and include inhalation of hyperpolarized helium to construct an image of the lungs.

Also known as: helium

Normal control; Severe asthma; Well controlled asthma

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects with asthma (severe asthma, well controlled asthma) and healthy normal controls from Madison, WI region

You may qualify if:

• Physician diagnosis of asthma
• Age 6 years and older
• Evidence of historical reversibility, including either:
• \. FEV1 bronchodilator reversibility ≥ 12%, or
• \. Airway hyperresponsiveness reflected by a methacholine PC20 ≤16 mg/mL.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Institutes of Health (NIH): collaborator
• Washington University School of Medicine: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

UW Madison

Madison, Wisconsin, 53792, United States

Location

Related Publications (4)

• 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.

  PMID: 38127464 DERIVED

• Dunican 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.

  PMID: 29400693 DERIVED

• Denlinger 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.

  PMID: 27556234 DERIVED

• Witt 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.

  PMID: 25018070 DERIVED

Related Links

• SARP Website

Biospecimen

Retention: SAMPLES WITH DNA

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

MeSH Terms

Conditions

Asthma; Lymphoma, Follicular

Interventions

Helium

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders

Intervention Hierarchy (Ancestors)

Noble Gases; Elements; Inorganic Chemicals; Gases

Study Officials

• Nizar N Jarjour, MD

  UW Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2012
• First Posted: January 4, 2013
• Study Start: November 28, 2012
• Primary Completion: March 24, 2020
• Study Completion: December 17, 2021
• Last Updated: August 2, 2023

Record last verified: 2023-07

Locations

US (1)