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Mechanism(s)of Airflow Limitation in Moderate-severe Persistent Asthma

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ClinicalTrials.gov Identifier: NCT00576069
Recruitment Status : Recruiting
First Posted : December 18, 2007
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
Arthur F Gelb MD, Gelb, Arthur F., M.D.

Tracking Information
First Submitted Date December 17, 2007
First Posted Date December 18, 2007
Last Update Posted Date August 20, 2019
Study Start Date October 2007
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 10, 2017)
  • use exhaled nitric oxide as a surrogate marker of large airway vs small airway/lung inflammation following various doses of inhaled corticosteroids [ Time Frame: 20-60 days ]
  • determine site of airflow limitation, whether predominantly large and /or small airways using expiratory flow volume curves obtained before and after asthmatics breathe a 80% helium-20% oxygen gas mixture [ Time Frame: 20-60 days ]
  • investigate the mechanisms that limit expiratory airflow: intrinsic airway obstruction vs loss of lung elastic recoil [ Time Frame: 20-60 days ]
  • determine the extent of asthma and distribution of emphysema [ Time Frame: within 10 days following death or explanted lung if lung transplant obtained ]
    at autopsy or post lung transplantation
Original Primary Outcome Measures
 (submitted: December 17, 2007)
  • use exhaled nitric oxide as a surrogate marker of large airway vs small airway/lung inflammation following various doses of inhaled corticosteroids [ Time Frame: 20-60 days ]
  • determine site of airflow limitation, whether predominantly large and /or small airways using expiratory flow volume curves obtained before and after asthmatics breathe a 80% helium-20% oxygen gas mixture [ Time Frame: 20-60 days ]
Change History
Current Secondary Outcome Measures
 (submitted: July 10, 2017)
  • dynamic hyperinflation [ Time Frame: 20-60 days ]
  • Evaluate large and small airways and lung parenchyma in autopsied or transplanted lung in asthmatics and look for unsuspected emphysema [ Time Frame: June 2018 ]
    If approved by surviving power of attorney, chronic non-smoking asthmatics who expire will undergo autopsy evaluation to evaluate extent of airway obstruction as well as presence of emphysema
  • Optical Coherence Tomography [ Time Frame: June 2015 ]
    When stable, chronic non-smoking asthmatics with persistent expiratory airflow obstruction will undergo OCT via flexible bronchoscopy to detect unsuspected emphysema.
Original Secondary Outcome Measures
 (submitted: December 17, 2007)
  • investigate the mechanisms that limit expiratory airflow: intrinsic airway obstruction vs loss of lung elastic recoil [ Time Frame: 20-60 days ]
  • dynamic hyperinflation [ Time Frame: 20-60 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Mechanism(s)of Airflow Limitation in Moderate-severe Persistent Asthma
Official Title Evaluation of Mechanism(s)Limiting Expiratory Airflow in Chronic, Stable Asthmatics Who Are Non-smokers
Brief Summary The purpose of this study is to evaluate the site and mechanisms responsible for expiratory airflow limitation in chronic, treated, non-smoking, stable asthmatics with moderate to severe persistent expiratory airflow obstruction. Treatment will include inhaled corticosteroids and long acting beta2agonists and long acting muscarinic antagonists. We are interested in determining whether the large and/or small airways are the predominant site of airflow limitation. We are also interested in determining whether intrinsic small airways obstruction and/or loss of lung elastic recoil is responsible for expiratory airflow limitation and to what extent may be attributed to loss of lung elastic recoil vs decreased airway conductance in peripheral airways. We are also interested to evaluate the role of varying doses of inhaled corticosteroids to suppress large and small airway inflammation using exhaled nitric oxide as surrogate markers of inflammation. For comparison purposes, spirometry and measurements of exhaled nitric oxide will also be obtained if possible during a naturally occurring exacerbation of asthma. High resolution thin section CT of the lung will also be obtained. Analysis will evaluate integrity of the lung parenchyma as to absence and or presence of emphysema and extent of emphysema using voxel quantification. We will also investigate optical coherence tomography to detect clinically unsuspected emphysema. We will also obtain autopsy material when available in asthmatics who expire. Will also measure serum periostin as a marker of inflammation by collaborating with Genetech in San Francisco.
Detailed Description Results will be evaluated during exacerbation and when stable following treatment.
Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Chronic Asthmatics
Condition Asthma
Intervention
  • Drug: budesonide/formoterol
    2 inhalations 2X/daily in treated arm/group. No placebo group
    Other Names:
    • symbicort 80/4.5
    • symbicort 160/4.5
    • budesonide 80 or 160ug/formoterol 4.5ug, 2 inhalations bid
    • spiriva handihaler or respihaler
  • Drug: fluticasone/salmeterol
    fluticasone 100ug/salmeterol 50ug, 1 inhalation bid noplacebo fluticasone 250ug/salmeterol 50ug, 1 inhalations bid no placebo Spiriva handihaler daily or respihaler 2 inhalations daily no placebo group
    Other Names:
    • advair 100/50
    • advair 250/50
  • Drug: mometasone/formoterol

    200/5 mcg two puffs bid 100/5 mcg two puffs bid Breo Ellipta once daily Spiriva capsule handihaler once daily or Spiriva respihaler 2 in

    no placebo group

    Other Name: Dulera
  • Drug: Prednisone
    0-15 mg daily as needed
    Other Name: medrol
Study Groups/Cohorts asthma, quality of life, lung function
All Asthmatics will be treated with 1 of 3 long acting beta 2 agonist + corticosteroid using low or medium dose of inhaled (Advair) fluticasone or equivalent corticosteroid 200-500mcg/day plus salmeterol 100 mcg/day or (Symbicort) budesonide 320-640 mcg +formoterol 18 mcg/day or (Dulera) mometasone 400-800mcg + formoterol 20 mcg/day. In addition tiotropium 18ucg/day will be used. Additionally, albuterol 0.083%/ipratropium 0.02% solution or MDI HFA for acute exacerbation.Will measure lung function and asthma quality of life questionaire
Interventions:
  • Drug: budesonide/formoterol
  • Drug: fluticasone/salmeterol
  • Drug: mometasone/formoterol
  • Drug: Prednisone
Publications *

*   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: July 10, 2017)
60
Original Estimated Enrollment
 (submitted: December 17, 2007)
40
Estimated Study Completion Date June 2022
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Current non-smoking (<10 pack yr smoking history)
  • Stable, treated asthmatics
  • Age 12-95 yr
  • post 180ug albuterol by MDI: FEV 1/FVC < 70% and FEV 1 <80% predicted

Exclusion Criteria:

  • Pregnancy
Sex/Gender
Sexes Eligible for Study: All
Ages 10 Years to 95 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Arthur F Gelb, MD 562-633-2204 afgelb@msn.com
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT00576069
Other Study ID Numbers 20070934
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: Yes
Plan Description: see publications
Responsible Party Arthur F Gelb MD, Gelb, Arthur F., M.D.
Study Sponsor Gelb, Arthur F., M.D.
Collaborators Not Provided
Investigators
Principal Investigator: Arthur F Gelb, MD Arthur F Gelb Medical Corporation
PRS Account Gelb, Arthur F., M.D.
Verification Date August 2019