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

October 25, 2023 updated by: Arthur F Gelb MD, Gelb, Arthur F., M.D.

Evaluation of Mechanism(s)Limiting Expiratory Airflow in Chronic, Stable Asthmatics Who Are Non-smokers

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Observational

Enrollment (Estimated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Arthur F Gelb, MD
  • Phone Number: 562-633-2204
  • Email: afgelb@msn.com

Study Locations

  • United States
    • California
      • Lakewood, California, United States, 90712
        • Recruiting
        • Arthur F Gelb Medical Corporation
        • Principal Investigator:
          • Arthur F Gelb, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 95 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Chronic Asthmatics

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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 Names:
  • Dulera
Drug: Prednisone
0-15 mg daily as needed
Other Names:
  • medrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
20-60 days
investigate the mechanisms that limit expiratory airflow: intrinsic airway obstruction vs loss of lung elastic recoil
Time Frame: 20-60 days
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
within 10 days following death or explanted lung if lung transplant obtained

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
dynamic hyperinflation
Time Frame: 20-60 days
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
June 2018
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.
June 2015

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gelb, Arthur F., M.D.

Investigators

  • Principal Investigator: Arthur F Gelb, MD, Arthur F Gelb Medical Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 25, 2007

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

December 17, 2007

First Submitted That Met QC Criteria

December 17, 2007

First Posted (Estimated)

December 18, 2007

Study Record Updates

Last Update Posted (Actual)

October 26, 2023

Last Update Submitted That Met QC Criteria

October 25, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20070934

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

see publications

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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