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

This study is currently recruiting participants.
Verified August 2016 by Arthur F Gelb MD, Gelb, Arthur F., M.D.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00576069
First Posted: December 18, 2007
Last Update Posted: July 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Arthur F Gelb MD, Gelb, Arthur F., M.D.
  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. Will also measure serum periostin as a marker of inflammation by collaborating with Genetech in San Francisco.

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

Study Type: Observational
Study Design: Observational Model: Case-Control
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 Arthur F Gelb MD, 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 ]
  • 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


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 60
Study Start Date: October 2007
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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
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

Detailed Description:
Results will be evaluated during exacerbation and when stable following treatment.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years to 95 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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:

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
First Submitted: December 17, 2007
First Posted: December 18, 2007
Last Update Posted: July 11, 2017
Last Verified: August 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: see publications

Keywords provided by Arthur F Gelb MD, 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
Prednisone
Fluticasone
Budesonide
Mometasone Furoate
Fluticasone Propionate, Salmeterol Xinafoate Drug Combination
Formoterol Fumarate
Salmeterol Xinafoate
Tiotropium Bromide
Budesonide, Formoterol Fumarate Drug Combination
Anti-Inflammatory Agents
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
Anti-Asthmatic Agents
Respiratory System Agents