Healthy VolunteersNCT01216748
Clinical Evidence of pH Dependent ß2 Adrenergic Transport Mechanisms in the Airway
A study testing quiet breathing, Hypocapnic Hyperventilation and Hypercapnic Hyperventilation in people with Healthy Volunteers, run by University of Miami at 1 site in United States.
Trial summary
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 Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- quiet breathing, Hypocapnic Hyperventilation and Hypercapnic Hyperventilation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2010to Aug 2010
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Lifetime non-smokers
- FEV1 > 80% predicted value and FEV1/FVC > 0.75
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Pulmonary Human Research Laboratory, University of Miami School of Medicine
Miami, Florida, 33136
About this study
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
Read the 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.
- Conditions
- Healthy Volunteers
- Being tested
- quiet breathing, Hypocapnic Hyperventilation, Hypercapnic Hyperventilation, eucapnic hyperventilation
- Keywords
- airway blood flow, albuterol, acidosis, alkalosis
- Medical subject headings
- Acidosis, Alkalosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
quiet breathingOther
Subjects were instructed to breath normally at room air.
Hypocapnic HyperventilationOther
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.
Hypercapnic HyperventilationOther
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
eucapnic hyperventilationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| health life-time non smokers | Experimental | health lifetime non-smokers will be challenged with 4 respiratory maneuvers:quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation Receives: Other: quiet breathing; Other: Hypocapnic Hyperventilation; Other: Hypercapnic Hyperventilation; Other: eucapnic hyperventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Airway Blood Flow After 180μg Albuterol by Inhalation (ΔQaw) vs Baseline
Effect of airway pH on albuterol responsiveness as reflected by the change in airway blood flow after 180μg albuterol by inhalation (ΔQaw) vs baseline.
Measured: 15 minutes after albuterol inhalation
Secondary outcomes (1)
Exhaled Breath Condensate (EBC) pH Variation
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.
Measured: 10 minutes after each respiratory manouver.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2010 (estimated)
- Study startJan 2010
- Primary completionJul 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by University of MiamiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Matthias Salathe, University of Miami
- Investigators
- Matthias Salathe, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01216748
- Sponsor's protocol ID
- 20070583
- Other IDs
- R01HL060644
- Status last verified
- Nov 2014
- First submitted
- 6 Oct 2010
- Last updated
- 27 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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.
PubMed 14680074Paget-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.
PubMed 16478862Horvath 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.
PubMed 16917073Cancado 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.
PubMed 25889594
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Evidence of pH Dependent ß2 Adrenergic Transport Mechanisms in the Airway
- ClinicalTrials.gov ID
- NCT01216748
- Acronym / sponsor ID
- 20070583
- Conditions
- Healthy Volunteers
- Keywords
- airway blood flow, albuterol, acidosis, alkalosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jan 2010
- Primary completion
- Jul 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 7 Oct 2010 (estimated)
- Results
- Posted 17 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| health life-time non smokers | Experimental | Other: quiet breathing, Other: Hypocapnic Hyperventilation, Other: Hypercapnic Hyperventilation, Other: eucapnic hyperventilationhealth lifetime non-smokers will be challenged with 4 respiratory maneuvers:quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Lifetime non-smokers
- FEV1 > 80% predicted value and FEV1/FVC > 0.75
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| quiet breathingSubjects were instructed to breath normally at room air. | Other | health life-time non smokers |
| Hypocapnic Hyperventilationhypocapnic 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. | Other | health life-time non smokers |
| Hypercapnic HyperventilationFor 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 | Other | health life-time non smokers |
| eucapnic hyperventilationFor 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. | Other | health life-time non smokers |
Primary outcome
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.
1 secondary outcome
Exhaled Breath Condensate (EBC) pH Variation
Time frame: 10 minutes after each respiratory manouver.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 14680074Vaughan 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.
- Background: PubMed 16478862Paget-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.
- Background: PubMed 16917073Horvath 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.
- Derived from this study: PubMed 25889594Cancado 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthias Salathe principal investigator
University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing quiet breathing, Hypocapnic Hyperventilation and Hypercapnic Hyperventilation in people with Healthy Volunteers, run by University of Miami at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Airway Blood Flow After 180μg Albuterol by Inhalation (ΔQaw) vs Baseline (time frame: 15 minutes after albuterol inhalation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01216748, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2016.