Mechanism(s) of Airflow Limitation During Exacerbation of Asthma

NCT01225913 | Recruiting Phase 4 DMC

• 1 other identifier: 20070934A
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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. The investigators are interested in determining whether the large and/or small airways are the predominant site of airflow limitation. The investigators are also interested in determining whether intrinsic small airways obstruction and/or loss of lung elastic recoil is responsible for expiratory airflow limitation. The investigators 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.

Conditions

Asthma

Keywords

asthma; lung function; inflammation

Outcome Measures

Primary Outcomes (1)

• Exhaled nitric oxide

  evaluate the role of inhaled corticosteroid on exhaled nitric oxide production in large airways and peripheral small airways/alveoli

  20-60 days

Secondary Outcomes (2)

• Mechanism(s) of expiratory airflow limitation

  1 to 5 years

• Presence of unsuspected emphysema by autopsy or explanted lung

  1-5 years

Study Arms (1)

Asthma observational study arm

OTHER

Asthmatics in this arm may be on varying dose of inhaled fluticasone 100-500mcg/salmeterol 50mcg bid via Advair MDI or equivalent dose via Diskus bid or Symbicort (budesonide 80-160mcg/formoterol 4.5mcg bid)or Dulera 100-200mcg mometasone/5 mcg formoterol bid, tiotropium 18mcg capsule daily. This is an observational study and additional pharmacologic intervention may include antibiotic and tapering doses of corticosteroids.

Drug: fluticasone/salmeterol in all asthmatics; Drug: budesonide/formoterol or fluticasone/salmeterol in all asthmatics

Interventions

fluticasone/salmeterol in all asthmatics DRUG

budesonide 80ug/formoterol 4.5ug, 2 inhalations bid X 20-60 days or fluticasone 100ug/salmeterol 50ug, 1 inhalation bid X 20-60 days

Also known as: symbicort 80/4.5, advair 100/50 or 250/50 or 500/50 bid

Asthma observational study arm

budesonide/formoterol or fluticasone/salmeterol in all asthmatics DRUG

budesonide 160ug/formoterol 4.5ug, 2 inhalations bid or fluticasone 250ug/salmeterol 50ug, 1 inhalations bid

Also known as: symbicort 160/4.5, advair 250/50

Asthma observational study arm

Eligibility Criteria

• Age: 10 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Pregnancy

Sponsors & Collaborators

• Gelb, Arthur F., M.D.: lead

Study Sites (1)

Arthur F Gelb Medical Corporation

Lakewood, California, 90712, United States

RECRUITING

Related Publications (14)

• Gelb AF, Zamel N. Unsuspected pseudophysiologic emphysema in chronic persistent asthma. Am J Respir Crit Care Med. 2000 Nov;162(5):1778-82. doi: 10.1164/ajrccm.162.5.2001037.

  PMID: 11069812 BACKGROUND

• 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. doi: 10.1378/chest.121.3.715.

  PMID: 11888951 BACKGROUND

• Gelb AF, Gutierrez CA, Weisman IM, Newsom R, Taylor CF, Zamel N. Simplified detection of dynamic hyperinflation. Chest. 2004 Dec;126(6):1855-60. doi: 10.1378/chest.126.6.1855.

  PMID: 15596684 BACKGROUND

• 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. doi: 10.1378/chest.129.6.1492.

  PMID: 16778266 BACKGROUND

• 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. doi: 10.1164/rccm.200403-408OC. Epub 2004 Jun 30.

  PMID: 15229098 BACKGROUND

• 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. doi: 10.1097/MCP.0b013e3282f197df.

  PMID: 18043272 BACKGROUND

• Gelb AF, Yamamoto A, Verbeken EK, Schein MJ, Moridzadeh R, Tran D, Fraser C, Barbers R, Elatre W, Koss MN, Glassy EF, Nadel JA. Further Studies of Unsuspected Emphysema in Nonsmoking Patients With Asthma With Persistent Expiratory Airflow Obstruction. Chest. 2018 Mar;153(3):618-629. doi: 10.1016/j.chest.2017.11.016. Epub 2017 Nov 29.

  PMID: 29197547 BACKGROUND

• Gelb AF, Moridzadeh R, Singh DH, Fraser C, George SC. In moderate-to-severe asthma patients monitoring exhaled nitric oxide during exacerbation is not a good predictor of spirometric response to oral corticosteroid. J Allergy Clin Immunol. 2012 Jun;129(6):1491-8. doi: 10.1016/j.jaci.2012.03.036. Epub 2012 May 2.

  PMID: 22560478 RESULT

• Gelb AF, Yamamoto A, Mauad T, Kollin J, Schein MJ, Nadel JA. Unsuspected mild emphysema in nonsmoking patients with chronic asthma with persistent airway obstruction. J Allergy Clin Immunol. 2014 Jan;133(1):263-5.e1-3. doi: 10.1016/j.jaci.2013.09.045. Epub 2013 Nov 28. No abstract available.

  PMID: 24290280 RESULT

• Gelb AF, Singh DH, Moridzadeh R, Fraser C, Tran D, Verbanck S, George SC. Age-stratified comparison of large and peripheral airway/alveolar nitric oxide levels in children and young adults. J Allergy Clin Immunol. 2013 Nov;132(5):1222-4. doi: 10.1016/j.jaci.2013.05.045. Epub 2013 Aug 6. No abstract available.

  PMID: 23932460 RESULT

• Senhorini A, Ferreira DS, Shiang C, Silva LF, Dolhnikoff M, Gelb AF, Mauad T. Airway dimensions in fatal asthma and fatal COPD: overlap in older patients. COPD. 2013 Jun;10(3):348-56. doi: 10.3109/15412555.2012.752806. Epub 2013 Mar 28.

  PMID: 23537051 RESULT

• Gelb AF, Yamamoto A, Verbeken EK, Nadel JA. Unraveling the Pathophysiology of the Asthma-COPD Overlap Syndrome: Unsuspected Mild Centrilobular Emphysema Is Responsible for Loss of Lung Elastic Recoil in Never Smokers With Asthma With Persistent Expiratory Airflow Limitation. Chest. 2015 Aug;148(2):313-320. doi: 10.1378/chest.14-2483.

  PMID: 25950858 RESULT

• Gelb AF, Christenson SA, Nadel JA. Understanding the pathophysiology of the asthma-chronic obstructive pulmonary disease overlap syndrome. Curr Opin Pulm Med. 2016 Mar;22(2):100-5. doi: 10.1097/MCP.0000000000000236.

  PMID: 26717511 RESULT

• Gelb AF, Nadel JA. Understanding the pathophysiology of the asthma-chronic obstructive pulmonary disease overlap syndrome. J Allergy Clin Immunol. 2015 Sep;136(3):553-5. doi: 10.1016/j.jaci.2015.06.013. No abstract available.

  PMID: 26343939 RESULT

MeSH Terms

Conditions

Asthma; Inflammation

Interventions

Fluticasone; Salmeterol Xinafoate; Budesonide; Formoterol Fumarate; Fluticasone-Salmeterol Drug Combination

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Pregnenediones; Pregnenes; Pregnanes; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Arthur F Gelb, MD

  Arthur F Gelb Medical Corporation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arthur F Gelb, MD

CONTACT

562-633-2204; afgelb@msn.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: To Better Understand the Mechanism(s) of Airflow Limitation During Exacerbation of Asthma

Study Record Dates

• First Submitted: October 19, 2010
• First Posted: October 21, 2010
• Study Start: October 1, 2007
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: October 26, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)