- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01216748
Clinical Evidence of pH Dependent ß2 Adrenergic Transport Mechanisms in the Airway
April 27, 2016 updated by: Matthias Salathe, University of Miami
The purpose of this study was to determine if airway pH has an effect on albuterol-induced vasodilation in the airway.
Methods: Ten healthy volunteers performed the following respiratory maneuvers: quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation
Study Overview
Status
Completed
Conditions
Detailed Description
The lungs provide a unique absorptive surface for drug delivery.
Many inhaled drugs are rapidly absorbed into the airway because of their lipophilic chemical characteristics.
However, the majority of the currently used β2-adrenergic bronchodilators cannot freely diffuse across the epithelial cell membrane because of their transient or permanent positive charge at physiological pH.
Inhaled albuterol, a β2-adrenergic agonist used widely for the treatment of obstructive airway disease, is charged positively in neutral or acidic conditions and thus requires active transport across the airway epithelium.
Previous studies in the lab have shown that albuterol uptake into airway epithelia occurs via a pH sensitive cation transporter (OCTN2).
The vasodilator response to an inhaled β2-adrenergic agonist could be an expression of epithelial cation transport.
The investigators propose that the magnitude and duration of vasodilation in the airway caused by an inhaled hydrophilic β2-adrenergic agonist such as albuterol may be altered by changes in airway pH.
The purpose of this protocol is to determine the effect of ASL pH on the response of Qaw to inhaled albuterol by manipulating airway pH through ventilatory maneuvers in health subjects: hyperventilation to raise pH and ventilation with CO2 bleed-in to lower pH.
Study Type
Interventional
Enrollment (Actual)
10
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Florida
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Miami, Florida, United States, 33136
- Pulmonary Human Research Laboratory, University of Miami School of Medicine
-
-
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
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Lifetime non-smokers
- FEV1 > 80% predicted value and FEV1/FVC > 0.75
Exclusion Criteria:
- Cardiovascular disease or use of cardiovascular or vasoactive drugs;
- Lung disease or use of airway drugs (i.e. inhaled corticosteroids, β adrenergic agonists);
- Respiratory infection during the 4 weeks preceding the study
- Use of systemic glucocorticoids within 4 weeks of the study
- Pregnant or nursing females
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
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: health life-time non smokers
health lifetime non-smokers will be challenged with 4 respiratory maneuvers:quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation
|
Subjects were instructed to breath normally at room air.
hypocapnic hyperventilation, the subjects were instructed to breathe fast and deep until their end-tidal pCO2 fell to 30 mmHg, corresponding to a systemic pH increase of about 0.1 pH units.
For hypercapnic hyperventilation, a modification of a previously described procedure (15).
While monitoring SaO2 using pulse oximetry and end-tidal CO2 by mass-spectrometry on a breath by breath basis, CO2 was bled into the inspired air to achieve an end-tidal pCO2 of at least 55 mmHg
For eucapnic hyperventilation, the subjects were instructed to increase their ventilation to the highest level of ventilation recorded in the previous two hyperventilation maneuvers, while CO2 was bled into the inspired air to maintain end-tidal pCO2 at 40 mmHg.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in Airway Blood Flow After 180μg Albuterol by Inhalation (ΔQaw) vs Baseline
Time Frame: 15 minutes after albuterol inhalation
|
Effect of airway pH on albuterol responsiveness as reflected by the change in airway blood flow after 180μg albuterol by inhalation (ΔQaw) vs baseline.
|
15 minutes after albuterol inhalation
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Exhaled Breath Condensate (EBC) pH Variation
Time Frame: 10 minutes after each respiratory manouver.
|
EBC samples were collected at each respiratory maneuver by directing the subject's exhaled breath into a pre-cooled (-10C) tube for 10 min. pH was measured immediately after collection. |
10 minutes after each respiratory manouver.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Matthias Salathe, University of Miami
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
- Vaughan J, Ngamtrakulpanit L, Pajewski TN, Turner R, Nguyen TA, Smith A, Urban P, Hom S, Gaston B, Hunt J. Exhaled breath condensate pH is a robust and reproducible assay of airway acidity. Eur Respir J. 2003 Dec;22(6):889-94. doi: 10.1183/09031936.03.00038803.
- Paget-Brown AO, Ngamtrakulpanit L, Smith A, Bunyan D, Hom S, Nguyen A, Hunt JF. Normative data for pH of exhaled breath condensate. Chest. 2006 Feb;129(2):426-430. doi: 10.1378/chest.129.2.426.
- Horvath G, Schmid N, Fragoso MA, Schmid A, Conner GE, Salathe M, Wanner A. Epithelial organic cation transporters ensure pH-dependent drug absorption in the airway. Am J Respir Cell Mol Biol. 2007 Jan;36(1):53-60. doi: 10.1165/rcmb.2006-0230OC. Epub 2006 Aug 17.
- Cancado JE, Mendes ES, Arana J, Horvath G, Monzon ME, Salathe M, Wanner A. Effect of airway acidosis and alkalosis on airway vascular smooth muscle responsiveness to albuterol. BMC Pharmacol Toxicol. 2015 Apr 2;16:9. doi: 10.1186/s40360-015-0008-y.
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
January 1, 2010
Primary Completion (Actual)
July 1, 2010
Study Completion (Actual)
August 1, 2010
Study Registration Dates
First Submitted
October 6, 2010
First Submitted That Met QC Criteria
October 6, 2010
First Posted (Estimate)
October 7, 2010
Study Record Updates
Last Update Posted (Estimate)
May 27, 2016
Last Update Submitted That Met QC Criteria
April 27, 2016
Last Verified
November 1, 2014
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- 20070583
- R01HL060644 (U.S. NIH Grant/Contract)
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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