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Characterizing Asthma Sputum Elasticity in the UCSF Severe Asthma Research Program (CAESAR)

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ClinicalTrials.gov Identifier: NCT02103348
Recruitment Status : Recruiting
First Posted : April 3, 2014
Last Update Posted : June 3, 2021
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco

Tracking Information
First Submitted Date March 24, 2014
First Posted Date April 3, 2014
Last Update Posted Date June 3, 2021
Study Start Date September 2015
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 31, 2014)
Lung function [ Time Frame: Cross sectional over 4-6 weeks ]
Lung function as a measure of asthma severity.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: March 31, 2014)
Inflammatory cellular markers [ Time Frame: Cross sectional over 4-6 weeks ]
Changes in inflammatory cellular markers in sputum and blood. We will measure various indicators of airway inflammation and compare them with various phenotypic characteristics.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: March 31, 2014)
CT Chest [ Time Frame: Cross sectional over 4-6 weeks ]
Examining CT chest in asthmatics for evidence of retained mucus.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title Characterizing Asthma Sputum Elasticity in the UCSF Severe Asthma Research Program
Official Title Characterizing Asthma Sputum Elasticity in the UCSF Severe Asthma Research Program
Brief Summary This study is designed to characterize subjects in terms of their sputum phenotype. The purpose of this study is to learn more about the impact of having abnormally elastic sputum on asthma severity by comparing subjects with severe as well as mild/moderate asthma to healthy controls. The characterization will include medical history, pulmonary function testing, imaging of the lungs and biospecimen collection.
Detailed Description

Asthma is a heterogeneous disease characterized by airway hyperreactivity and chronic airway inflammation. Published literature from the last few years has shown that asthma does not behave like a single disease but is more of a syndrome with vast heterogeneity in pathogenesis, severity, and treatment response. Various clinical phenotypes and endotypes have been described that advance our understanding of these differences and the mechanisms underlying them. We propose there is a subgroup of asthmatic patients that have sputum with abnormal biophysical properties. Healthy airway mucus is composed of a lightly cross-linked gel that is easily transported by the mucociliary apparatus, coughed and expectorated or swallowed. Pathologic mucus has, in contrast, abnormally high elasticity. This is due to a more cross linked structure which gives the sputum the properties of solid and makes sputum difficult to mobilize. Increased sputum elasticity makes expectoration of sputum more difficult and leads to airflow obstruction. Pathologic mucus contributes to airflow obstruction and airway infection in multiple lung diseases, including asthma. Mucus plugs are a particular problem in asthmatic patients with allergic bronchopulmonary aspergillosis (ABPA)The identification of phenotype of severe asthma with pathologic mucus contributing to disease severity may change how we think about severe asthma, moving towards therapies targeting mucus clearance such as in other conditions such as cystic fibrosis. Pathologic mucus in severe asthma is characterized by cellular inflammation, high concentrations of mucins and DNA polymers. Knowledge of specific cellular and biochemical constituents of pathologic mucus in severe asthma can guide targeted mucolytic treatment with n-acetylcysteine, rhDNAse, or novel mucolytic agents.

As part of the Severe Asthma Research Program (SARP), UCSF is in a unique position to recruit a large number of severe asthmatic subjects within which we expect a portion will demonstrate high sputum elasticity. We will also through CAESAR recruit additional subjects with moderate to severe airflow obstruction. We will perform rheological measurement on all subjects that are recruited to our site and from this identify a group of asthmatic cases that have an elastic modulus of ≥1 or <1 and compare properties of sputum from these subjects to healthy controls.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Samples of induced sputum and blood for DNA and RNA extraction, plasma, and serum will be banked in the UCSF Airway Tissue Bank.
Sampling Method Non-Probability Sample
Study Population A diverse sample of subjects with asthma is needed to gain better understanding of asthma and its endotypes. CAESAR will therefore enroll subjects between 18 and 65 years with a physician diagnosis of asthma as well as a group of healthy subjects. The target recruitment goal for UCSF is 50 adults with asthma and 25 healthy controls (age 18 and older). Within the asthma group, an attempt will be made to enroll 60% of subjects with severe with the rest of the subjects mild to moderate asthma.Within the cohort, an attempt will be made to enroll at least 50% females and 10% minorities.
Condition Asthma
Intervention Not Provided
Study Groups/Cohorts
  • Mild-to-Moderate Asthma
    Those with mild-to-moderate persistent asthma as defined by the NAEPP EPR-3 guidelines.
  • Severe Asthma

    Major Criteria: (1 required)

    1. Treatment with oral corticosteroids for at least 6 of the previous 12 months
    2. Treatment with high-dose inhaled corticosteroids for at least 10 of the previous 12 months

    Minor Criteria: (2 required)

    1. Daily treatment with an asthma controller medication in addition to inhaled, or
    2. Asthma symptoms requiring short-acting bronchodilator use on a daily or near daily basis (defined as at least 5 of 7 days), or
    3. Persistent airway obstruction with baseline FEV1 <80% predicted, or
    4. ≥ 1 urgent visits for asthma in the previous 12 months, or
    5. ≥ 3 systemic corticosteroid bursts in the previous 12 months, or
    6. Prompt deterioration with a reduction in oral or inhaled corticosteroid dose, or
    7. A near-fatal asthma event (i.e., intubation) in the past.
  • Healthy Controls
    Those without asthma or other chronic lung disease.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: March 31, 2014)
75
Original Estimated Enrollment Same as current
Estimated Study Completion Date June 2023
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • FEV1 bronchodilator reversibility ≥12% or airway hyperresponsiveness reflected by a methacholine PC20 ≤16 mg/mL
  • An exception will be made for enrollees whose FEV1 is < 50% predicted (<70% in children aged 6 to 17 years), precluding methacholine challenge testing. If bronchodilator reversibility is <12% in these participants, a diagnosis of asthma acceptable to the investigator is sufficient for inclusion in CAESAR.

Exclusion Criteria:

  • Pregnancy,
  • Current smoking,
  • Smoking history > 10 pack years if ≥30 years of age, or smoking history > 5 pack years if <30 years of age,
  • 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 respiratory symptoms and at the PI's discretion), 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,
  • Planning to relocate from the clinical center area before study completion,
  • 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, or
  • Currently participating in an investigational drug trial.

Healthy Controls:

Inclusion criteria: Healthy subjects between the age of 18y and 65y. At least 3 of the 7 subjects per center should be aged 35y or older.

Exclusion criteria

  • History of chronic diseases that affect the lungs.
  • A history suggestive of allergic rhinitis, eczema or chronic sinusitis.
  • An improvement in FEV1 of more than 12% following 4 puffs of albuterol.
  • Smoking history > 10 pack years if ≥30 years of age, or smoking history > 5 pack years if <30 years of age, or any smoking within the past year.
  • Respiratory tract infection within the past 4 weeks.
  • Pregnancy.
  • History of premature birth (<35 weeks).
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Gina M Grayson 415-502-3472 Gina.Evans-Young@ucsf.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02103348
Other Study ID Numbers 14-13242
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party University of California, San Francisco
Study Sponsor University of California, San Francisco
Collaborators Not Provided
Investigators
Principal Investigator: John V Fahy, M.D. M.SC. University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date June 2021