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Acute Airway Vascular Smooth Muscle Effects of Inhaled Budesonide

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Eliana Mendes, University of Miami
ClinicalTrials.gov Identifier:
NCT01219738
First received: October 12, 2010
Last updated: January 7, 2015
Last verified: January 2015
  Purpose
Glucocorticosteroids recently have been shown to have non-genomic actions that are plasma membrane-mediated and do not require gene transcription and translation. One of these non-genomic effects is the inhibition of adrenergic agonist transport into airway vascular smooth muscle cells with an increase of adrenergic agonist concentrations at adrenergic receptor sites and enhance the physiological effects of endogenous adrenergic agonists (e.g. locally released norepinephrine from noradrenergic neurons) or exogenous adrenergic agonists (e.g. inhaled beta-adrenergic agonists).

Condition Intervention
Asthma
Drug: Budesonide 360ug
Drug: Budesonide 720ug
Drug: Budesonide 1440ug
Drug: Budesonide720ug 4 times
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Acute Airway Vascular Smooth Muscle Effects of Inhaled Budesonide

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Airway Blood Flow (Qaw) [ Time Frame: participants will be followed for 6 hours after budesonide dose ] [ Designated as safety issue: No ]
    Qaw will be measured before and up to 6 hours after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo from a DPI, using a double-blinded randomized design on different days.


Secondary Outcome Measures:
  • Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: participant will be followed up to 6 hours after budesonide dose ] [ Designated as safety issue: No ]
    FEV1 will be measured before and up to 6 hours after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo from a DPI, using a double-blinded randomized design on different days.


Enrollment: 20
Study Start Date: July 2008
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: budesonide 360ug
asthmatic subject received different doses of inhaled budesonide in random other
Drug: Budesonide 360ug
A single inhaled dose of 360ug budesonide from a DPI.
Other Name: Pulmicort Flexhaler
Experimental: budesonide 720ug
asthmatic subject received different doses of inhaled budesonide in random other
Drug: Budesonide 720ug
A single inhaled dose of 720ug budesonide from a DPI.
Other Name: Pulmicort Flexhaler
Experimental: budesonide 1440ug
asthmatic subject received different doses of inhaled budesonide in random other
Drug: Budesonide 1440ug
A single dose of 1440ug of the budesonide from DPI.
Other Name: Pulmicort Flexhaler
Placebo Comparator: placebo
asthmatic subject received inhaled placebo
Drug: Budesonide720ug 4 times
720ug of budesonide will be inhaled by the subjects 4 times, separated by 30 minutes.
Other Name: Pulmicort Flexhaler
Experimental: Budesonide720ug 4 times
asthmatic subject received 720ug of inhaled budesonide 4 times separated by 30 minutes.
Drug: Placebo
A single inhaled dose of placebo from a DPI.
Other Name: sugar pill

Detailed Description:
Inhaled glucocorticosteroids typically are not recommended for the treatment of acute asthma attacks. This practice is based on the fact that glucocorticosteroids by themselves do not cause rapid bronchodilation. However, the acute inhibition of adrenergic agonist disposal by the non-genomic action of glucocorticosteroids could lead to bronchial vasoconstriction by locally released norepinephrine thereby decongesting the airway wall, and potentiate the bronchodilator effect of a concomitantly administered beta-adrenergic agonist through the same mechanism. The purpose of this study is to assess the vasoconstrictive effects of single and repetitive high-dose budesonide inhalations in moderate to severe asthmatics who use inhaled glucocorticosteroids regularly. As a secondary endpoint, airway inflammation and airway function will also be measured with the expectation that acute improvements in airflow might be detectable as a result of airway decongestion, notably in subjects with moderately severe asthma who have lower baseline lung function.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Twenty lifetime nonsmokers moderate or severe asthmatics; FEV1≥50 of predicted on the screening day

Exclusion Criteria:

Women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women; Cardiovascular disease and/or use of cardiovascular medication; Subjects with known beta-adrenergic agonist or glucocorticosteroid intolerance; Acute respiratory infection and or acute exacerbation of asthma within four weeks prior to the study; Use of systemic glucocorticosteroids within 4 weeks prior to the study; Daily ICS dose (fluticasone or budesonide) > 500ug; Diabetes mellitus

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01219738

Locations
United States, Florida
Pulmonary Human Research Laboratory, University of Miami, Miller School of Medicine
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
AstraZeneca
Investigators
Principal Investigator: Eliana Mendes, MD University of Miami
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eliana Mendes, University of Miami
ClinicalTrials.gov Identifier: NCT01219738     History of Changes
Other Study ID Numbers: 20071068  IRUSBUPF0002 
Study First Received: October 12, 2010
Results First Received: November 12, 2014
Last Updated: January 7, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by University of Miami:
Asthma, airway blood flow, budesonide, glucocorticosteroid.

Additional relevant MeSH terms:
Budesonide
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 23, 2016