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

NCT ID: NCT00576069

Last Updated: 2023-10-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2007-10-25

Study Completion Date

2027-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Asthma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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

budesonide/formoterol

Intervention Type DRUG

2 inhalations 2X/daily in treated arm/group. No placebo group

fluticasone/salmeterol

Intervention Type DRUG

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

mometasone/formoterol

Intervention Type DRUG

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

Prednisone

Intervention Type DRUG

0-15 mg daily as needed

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

budesonide/formoterol

2 inhalations 2X/daily in treated arm/group. No placebo group

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

Prednisone

0-15 mg daily as needed

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

symbicort 80/4.5 symbicort 160/4.5 budesonide 80 or 160ug/formoterol 4.5ug, 2 inhalations bid spiriva handihaler or respihaler advair 100/50 advair 250/50 Dulera medrol

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

10 Years

Maximum Eligible Age

95 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Gelb, Arthur F., M.D.

INDIV

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Arthur F Gelb MD

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Arthur F Gelb, MD

Role: PRINCIPAL_INVESTIGATOR

Arthur F Gelb Medical Corporation

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Arthur F Gelb Medical Corporation

Lakewood, California, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Arthur F Gelb, MD

Role: CONTACT

562-633-2204

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 11069812 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11888951 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15596684 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16778266 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15229098 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18043272 (View on PubMed)

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.

Reference Type RESULT
PMID: 22560478 (View on PubMed)

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.

Reference Type RESULT
PMID: 24290280 (View on PubMed)

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.

Reference Type RESULT
PMID: 23932460 (View on PubMed)

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.

Reference Type RESULT
PMID: 25950858 (View on PubMed)

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.

Reference Type RESULT
PMID: 26343939 (View on PubMed)

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.

Reference Type RESULT
PMID: 26717511 (View on PubMed)

Gelb AF, Yamamoto A, Verbeken E, Grigorian SR, Nadel JA. Asthma and emphysema overlap in nonsmokers. Ann Allergy Asthma Immunol. 2020 Dec;125(6):711-713. doi: 10.1016/j.anai.2020.08.010. Epub 2020 Aug 10. No abstract available.

Reference Type DERIVED
PMID: 32791102 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29197547 (View on PubMed)

Gelb AF, George SC, Camacho F, Fraser C, Flynn Taylor C, Shakkottai S. Increased nitric oxide concentrations in the small airway of older normal subjects. Chest. 2011 Feb;139(2):368-375. doi: 10.1378/chest.10-1157. Epub 2010 Aug 12.

Reference Type DERIVED
PMID: 20705799 (View on PubMed)

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. doi: 10.1136/thx.2009.132696.

Reference Type DERIVED
PMID: 20627920 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

20070934

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Long-acting Beta Agonist Step Down Study
NCT01437995 COMPLETED PHASE4