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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Gelb, Arthur F., M.D.
Sponsor:
Information provided by (Responsible Party):
Arthur F Gelb MD, Gelb, Arthur F., M.D.
ClinicalTrials.gov Identifier:
NCT00576069
First received: December 17, 2007
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Asthma
Drug: budesonide/formoterol
Drug: fluticasone/salmeterol
Drug: mometasone/formoterol
Drug: Prednisone
Phase 4

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Evaluation of Mechanism(s)Limiting Expiratory Airflow in Chronic, Stable Asthmatics Who Are Non-smokers

Resource links provided by NLM:


Further study details as provided by Gelb, Arthur F., M.D.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • investigate the mechanisms that limit expiratory airflow: intrinsic airway obstruction vs loss of lung elastic recoil [ Time Frame: 20-60 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • dynamic hyperinflation [ Time Frame: 20-60 days ] [ Designated as safety issue: No ]
  • Evaluate large and small airways and lung parenchyma in autopsied asthmatics and look for unsuspected emphysema [ Time Frame: June 2015 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    When stable, chronic non-smoking asthmatics with persistent expiratory airflow obstruction will undergo OCT via flexible bronchoscopy to detect unsuspected emphysema.


Estimated Enrollment: 40
Study Start Date: October 2007
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
asthma, quality of life, lung function
low or medium dose of inhaled fluticasone or equivalent corticosteroid 200-500mcg/day plus salmeterol 100 mcg/day or formoterol 24 mcg/day plus tiotropium 18ucg/day plus albuterol0.083%/ipratropium 0.02% or MDI for acute exacerbation.Will measure lung function and asthma quality of life questionaire
Drug: budesonide/formoterol
budesonide 80ug/formoterol 4.5ug, 2 inhalations bid X 20-60 days or budesonide 160ug/formoterol 4.5ug, 2 inhalations bid X 20-60 days
Other Names:
  • symbicort 80/4.5
  • symbicort 160/4.5
Drug: fluticasone/salmeterol
fluticasone 100ug/salmeterol 50ug, 1 inhalation bid X 20-60 days or fluticasone 250ug/salmeterol 50ug, 1 inhalations bid
Other Names:
  • advair 100/50
  • advair 250/50
Drug: mometasone/formoterol
200/5 mcg two puffs bid
Other Name: Dulera
Drug: Prednisone
0-15 mg daily as needed

Detailed Description:

Results will be evaluated during exacerbation and when stable following treatment.

  Eligibility

Ages Eligible for Study:   10 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Chronic Asthmatics

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00576069

Contacts
Contact: Arthur F Gelb, MD 562-633-2204 afgelb@msn.com

Locations
United States, California
Arthur F Gelb Medical Corporation Recruiting
Lakewood, California, United States, 90712
Principal Investigator: Arthur F Gelb, MD         
Sponsors and Collaborators
Gelb, Arthur F., M.D.
Investigators
Principal Investigator: Arthur F Gelb, MD Arthur F Gelb Medical Corporation
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Arthur F Gelb MD, Principal Investigator, Gelb, Arthur F., M.D.
ClinicalTrials.gov Identifier: NCT00576069     History of Changes
Other Study ID Numbers: 20070934
Study First Received: December 17, 2007
Last Updated: March 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Gelb, Arthur F., M.D.:
asthma
lung function
inflammation

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Mometasone furoate
Fluticasone
Prednisone
Budesonide
Fluticasone, salmeterol drug combination
Formoterol
Salmeterol
Albuterol
Symbicort
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on August 26, 2014