COPDPhase 2NCT01209715
Effect of an Inhaled Glucocorticoid-long-acting Beta Adrenergic Agonist on Endothelial Function in COPD
A Phase 2 study testing Fluticasone /salmeterol in people with COPD, run by University of Miami at 1 site in United States.
Trial summary
In the present study, the investigators wish to address the effect of a glucocorticoid/long-acting beta-agonist preparation on endothelial function in COPD patients who do not currently smoke (ex-smokers) by measuring endothelium-dependent (albuterol response) and endothelium-independent (NTG response) vasodilation in… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- COPD
- What is being tested?
- Fluticasone /salmeterol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2010to May 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Smoking history of at least 10 pack-years and to have quit smoking at least 1 year before the study. -Diagnosis of COPD
- Post-bronchodilator FEV1 of less than 75% of predicted and FEV1/FVC ratio less than 0.7 (GOLD stage ≥2).
- At entry into the study, the subjects will have to be clinically stable; they will be allowed to use short-acting and long-acting β2 - adrenergic agonists and cholinergic antagonists as their usual airway medication.
Who cannot join
- Women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women.
- Use of cardiovascular medications that cannot be held on the study days
- Use of oral airway medications or anti-inflammatory agents
- Subjects with known beta-adrenergic agonist or NTG intolerance
- Acute respiratory infection within four weeks prior to the study
- A body mass index > 30
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Miami School of Medicine
Miami, Florida, 33136
About this study
In the present study, the investigators wish to address the effect of a glucocorticoid/long-acting beta-agonist preparation on endothelial function in COPD patients who do not currently smoke (ex-smokers) by measuring endothelium-dependent (albuterol response) and endothelium-independent (NTG response) vasodilation in the bronchial artery, reflecting endothelium-dependent and endothelium-independent vasodilation (drug-induced increase in Qaw, ΔQaw). With this approach the investigators will test the hypothesis that in stable ICS-naïve COPD patients, endothelium-dependent vasodilation is restored with a glucocorticoid/long-acting beta-agonist preparation, presumably resulting from the glucocorticoid component.
Read the detailed description
To test the premise and to characterize the time dependence of the responses, the investigators propose the following two aims:
- To determine the effect of a medium dose glucocorticoid/long-acting beta-agonist preparation (250 μg fluticasone plus 50 μg salmeterol) administered for 3 weeks on inhaled albuterol and sub-lingual NTG induced vasodilation in the bronchial artery, as assessed by ΔQaw in stable glucocorticoid-naïve COPD patients, and to re-assess the responses after a 3 week glucocorticoid/long-acting beta-agonist washout period.
- To determine inhaled albuterol and sub-lingual NTG-induced vasodilation (ΔQaw) before, and 30 min and 120 min after a single medium dose of an ICS (220 μg fluticasone) in stable glucocorticoid- naïve COPD patients.
For both aims, the protocol design will be placebo-controlled and double-blind. For the second aim, only fluticasone pretreatment will be possible because the salmeterol component of the fluticasone/salmeterol combination preparation could influence albuterol responsiveness irrespective of any glucocorticoid effect. The timing of the endothelial function measurements in the long-term glucocorticoid/long-acting beta-agonist protocol and single dose ICS protocol is based on the past experience with ICS on airway vascular function. Single dose effects were seen within 15-30 min and waned by 90 min (25,26), while long-term treatment effects were no longer seen 3 weeks after ICS withdrawal (16).
- Conditions
- COPD
- Being tested
- Placebo, Fluticasone /salmeterol
- Keywords
- airway blood flow,, COPD,, endothelial dysfunction, inhaled corticosteroids
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
participants will be assigned to 3-weeks treatment of inhaled placebo twice a day
Fluticasone /salmeterolDrug
Also called Advair 250/50
Participant will be assigned to a 3-weeks treatment with inhaled fluticasone/salmeterol or matching placebo
| Study group | Role | What they receive |
|---|---|---|
| Matching Placebo | Placebo comparator | Participants will be treated with placebo twice a day for 3 weeks. Receives: Drug: Placebo; Drug: Fluticasone /salmeterol |
| Fluticasone/salmeterol | Active comparator | Participants will be assigned to inhaled fluticasone/salmeterol twice a day for 3 weeks. Receives: Drug: Fluticasone /salmeterol |
What is being measured
The primary outcome is the main question the study is designed to answer.
long term effect of a glucocorticoid/long-acting beta-agonist on endothelial function in the bronchial artery.
To determine the effect of a medium dose glucocorticoid/long-acting beta-agonist preparation (250 μg fluticasone plus 50 μg salmeterol) or placebo administered for 3 weeks on inhaled albuterol and sub-lingual NTG induced vasodilation in the bronchial artery, as assessed by ΔQaw in stable glucocorticoid-naïve COPD patients, and to re-assess the responses after a 3 week washout period.
Measured: 3 weeks
Secondary outcomes (1)
acute effect of an ICS on bronchial endothelial function in stable glucocorticoid-naïve COPD patient.
To determine inhaled albuterol and sub-lingual NTG-induced vasodilation (ΔQaw) before, and 30 min and 120 minutes after a single medium dose of an ICS (220 μg fluticasone)or placebo in stable glucocorticoid-naïve COPD patients
Measured: 30 minutes and 120 minutes after inhaled albuterol and sub-lingual NTG
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2010 (estimated)
- Study startOct 2010
- Primary completionMay 2012
- Study completionMay 2012
Why it stopped: Due to the ubiquitous use of ICS in the treatment of COPD in 2012, it was hard to find the study population.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COPDStudies 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 2
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Adam Wanner, University of Miami
- Investigators
- Adam Wanner, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01209715
- Sponsor's protocol ID
- 114279
- Status last verified
- Jul 2014
- First submitted
- 24 Sep 2010
- Last updated
- 1 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of an Inhaled Glucocorticoid-long-acting Beta Adrenergic Agonist on Endothelial Function in COPD
- ClinicalTrials.gov ID
- NCT01209715
- Acronym / sponsor ID
- 114279
- Conditions
- COPD
- Keywords
- airway blood flow,, COPD,, endothelial dysfunction, inhaled corticosteroids
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Due to the ubiquitous use of ICS in the treatment of COPD in 2012, it was hard to find the study population.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 27 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the present study, the investigators wish to address the effect of a glucocorticoid/long-acting beta-agonist preparation on endothelial function in COPD patients who do not currently smoke (ex-smokers) by measuring endothelium-dependent (albuterol response) and endothelium-independent (NTG response) vasodilation in the bronchial artery, reflecting endothelium-dependent and endothelium-independent vasodilation (drug-induced increase in Qaw, ΔQaw). With this approach the investigators will test the hypothesis that in stable ICS-naïve COPD patients, endothelium-dependent vasodilation is restored with a glucocorticoid/long-acting beta-agonist preparation, presumably resulting from the glucocorticoid component.
Detailed description
To test the premise and to characterize the time dependence of the responses, the investigators propose the following two aims:
- To determine the effect of a medium dose glucocorticoid/long-acting beta-agonist preparation (250 μg fluticasone plus 50 μg salmeterol) administered for 3 weeks on inhaled albuterol and sub-lingual NTG induced vasodilation in the bronchial artery, as assessed by ΔQaw in stable glucocorticoid-naïve COPD patients, and to re-assess the responses after a 3 week glucocorticoid/long-acting beta-agonist washout period.
- To determine inhaled albuterol and sub-lingual NTG-induced vasodilation (ΔQaw) before, and 30 min and 120 min after a single medium dose of an ICS (220 μg fluticasone) in stable glucocorticoid- naïve COPD patients.
For both aims, the protocol design will be placebo-controlled and double-blind. For the second aim, only fluticasone pretreatment will be possible because the salmeterol component of the fluticasone/salmeterol combination preparation could influence albuterol responsiveness irrespective of any glucocorticoid effect. The timing of the endothelial function measurements in the long-term glucocorticoid/long-acting beta-agonist protocol and single dose ICS protocol is based on the past experience with ICS on airway vascular function. Single dose effects were seen within 15-30 min and waned by 90 min (25,26), while long-term treatment effects were no longer seen 3 weeks after ICS withdrawal (16).
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Matching Placebo | Placebo comparator | Drug: Placebo, Drug: Fluticasone /salmeterolParticipants will be treated with placebo twice a day for 3 weeks. |
| Fluticasone/salmeterol | Active comparator | Drug: Fluticasone /salmeterolParticipants will be assigned to inhaled fluticasone/salmeterol twice a day for 3 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Smoking history of at least 10 pack-years and to have quit smoking at least 1 year before the study. -Diagnosis of COPD
- Post-bronchodilator FEV1 of less than 75% of predicted and FEV1/FVC ratio less than 0.7 (GOLD stage ≥2).
- At entry into the study, the subjects will have to be clinically stable; they will be allowed to use short-acting and long-acting β2 - adrenergic agonists and cholinergic antagonists as their usual airway medication.
Key exclusion criteria (6 listed)
- Women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women.
- Use of cardiovascular medications that cannot be held on the study days
- Use of oral airway medications or anti-inflammatory agents
- Subjects with known beta-adrenergic agonist or NTG intolerance
- Acute respiratory infection within four weeks prior to the study
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 |
|---|---|---|
| Placeboparticipants will be assigned to 3-weeks treatment of inhaled placebo twice a day | Drug | Matching Placebo |
| Fluticasone /salmeterolAlso: Advair 250/50Participant will be assigned to a 3-weeks treatment with inhaled fluticasone/salmeterol or matching placebo | Drug | Fluticasone/salmeterol, Matching Placebo |
Primary outcome
long term effect of a glucocorticoid/long-acting beta-agonist on endothelial function in the bronchial artery.
Time frame: 3 weeks
To determine the effect of a medium dose glucocorticoid/long-acting beta-agonist preparation (250 μg fluticasone plus 50 μg salmeterol) or placebo administered for 3 weeks on inhaled albuterol and sub-lingual NTG induced vasodilation in the bronchial artery, as assessed by ΔQaw in stable glucocorticoid-naïve COPD patients, and to re-assess the responses after a 3 week washout period.
1 secondary outcome
acute effect of an ICS on bronchial endothelial function in stable glucocorticoid-naïve COPD patient.
Time frame: 30 minutes and 120 minutes after inhaled albuterol and sub-lingual NTG
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2014.
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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.
Adam Wanner, MD 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 Phase 2 study testing Fluticasone /salmeterol in people with COPD, 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 3 inclusion and 6 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: withdrawn, as of the sponsor's last update on 1 Aug 2014. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
long term effect of a glucocorticoid/long-acting beta-agonist on endothelial function in the bronchial artery. (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Aug 2014.