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

Sponsor:	Gelb, Arthur F., M.D.
Information provided by (Responsible Party):	Arthur F Gelb MD, Gelb, Arthur F., M.D.
ClinicalTrials.gov Identifier:	NCT00576069

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. 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. 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.

Condition	Intervention	Phase
Asthma	Drug: budesonide/formoterol or fluticasone/salmeterol	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Bio-availability Study Intervention Model: Crossover Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Evaluation of Mechanism(s)Limiting Expiratory Airflow in Chronic, Stable Asthmatics Who Are Non-smokers

Resource links provided by NLM:

MedlinePlus related topics: Asthma Choking

Drug Information available for: Formoterol fumarate Budesonide Arformoterol Formoterol Fluticasone propionate Salmeterol Fluticasone Salmeterol xinafoate Advair Symbicort Arformoterol Tartrate

U.S. FDA Resources

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 ]

Secondary Outcome Measures:

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 ]
dynamic hyperinflation [ Time Frame: 20-60 days ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	October 2007
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 low to moderate dose inhaled corticosteroid, long acting beta 2 agonist, tiotropium	Drug: budesonide/formoterol or fluticasone/salmeterol budesonide 80ug/formoterol 4.5ug, 2 inhalations bid X 20-60 days or fluticasone 100ug/salmeterol 50ug, 1 inhalation bid X 20-60 days Other Names: symbicort 80/4.5 advair 100/50
Experimental: 2 tapering dose of oral corticosteroid	Drug: budesonide/formoterol or fluticasone/salmeterol budesonide 160ug/formoterol 4.5ug, 2 inhalations bid or fluticasone 250ug/salmeterol 50ug, 1 inhalations bid Other Names: symbicort 160/4.5 advair 250/50

Detailed Description:

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

Eligibility

Ages Eligible for Study:	10 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

Pregnancy

Contacts and Locations

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:

Gelb AF, Zamel N. Unsuspected pseudophysiologic emphysema in chronic persistent asthma. Am J Respir Crit Care Med. 2000 Nov;162(5):1778-82.

Gelb AF, Licuanan J, Shinar CM, Zamel N. Unsuspected loss of lung elastic recoil in chronic persistent asthma. Chest. 2002 Mar;121(3):715-21.

Gelb AF, Gutierrez CA, Weisman IM, Newsom R, Taylor CF, Zamel N. Simplified detection of dynamic hyperinflation. Chest. 2004 Dec;126(6):1855-60.

Gelb AF, Flynn Taylor C, Shinar CM, Gutierrez C, Zamel N. Role of spirometry and exhaled nitric oxide to predict exacerbations in treated asthmatics. Chest. 2006 Jun;129(6):1492-9.

Gelb AF, Taylor CF, Nussbaum E, Gutierrez C, Schein A, Shinar CM, Schein MJ, Epstein JD, Zamel N. Alveolar and airway sites of nitric oxide inflammation in treated asthma. Am J Respir Crit Care Med. 2004 Oct 1;170(7):737-41. Epub 2004 Jun 30.

Gelb AF, Zamel N, Krishnan A. Physiologic similarities and differences between asthma and chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2008 Jan;14(1):24-30. Review.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gelb AF, George SC, Camacho F, Fraser C, Taylor CF, Shakkottai S. INCREASED PERIPHERAL AIRWAY/ALVEOLAR NITRIC OXIDE IN OLDER NORMALS. Chest. 2010 Aug 12; [Epub ahead of print]

Gelb AF, George SC, Silkoff PE, Krishnan A, Fraser C, Taylor CF, Shinar CM, Maginot T. Central and peripheral airway/alveolar sites of exhaled nitric oxide in acute asthma. Thorax. 2010 Jul;65(7):619-25.

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:	August 22, 2011
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
Budesonide
Formoterol
Salmeterol
Albuterol
Fluticasone
Fluticasone, salmeterol drug combination

Symbicort
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Inflammatory Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists

ClinicalTrials.gov processed this record on February 09, 2012