COPDPhase 1/2NCT02097992
Effect of Roflumilast on Airway Blood Flow as an Expression of Airway Inflammation in COPD
A Phase 1/2 study testing Roflumilast in people with COPD, run by University of Miami at 1 site in United States.
Trial summary
The objectives of the proposed study are to determine 1) the effect of a single dose of Roflumilast on airway blood flow (Qaw) (study period 1) and 2) the effect of long-term Roflumilast treatment on airway blood flow reactivity delta Qaw)(study period 2) in patients with stable COPD who use ICS regularly. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- COPD
- What is being tested?
- Roflumilast
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2013to Jul 2015
- Phase
- Phase 1/2
- 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 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Twenty-four patients with physician-diagnosed COPD (female and male, current smokers or ex-smokers) over the age of 45 years will be recruited for this study.
- The patients will have to have a smoking history of at least 10 pack-years, and they must have been using an ICS regularly for at least 4 weeks at the time of screening.
- Confirmation of the diagnosis of COPD will require the presence of persistent exertional dyspnea and a post-bronchodilator FEV1 of less than 80% of predicted and FEV1/FVC ratio less than 0.7 (GOLD stage ≥2). At entry into the study, the patients will have to be clinically stable; they will be allowed to remain on their regular COPD treatment regimen and use a LABA and/or LAMA until 24 hours before, and a SABA and/or short-acting muscarinic antagonist (SAMA) until 6 hours before coming to the laboratory. If using roflumilast, the subjects will have to discontinue it 4 weeks before entering into the study.-
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
- Use of supplemental oxygen that cannot be discontinued during the laboratory visit
- Subjects with known SABA or roflumilast intolerance
- An acute COPD exacerbation within four weeks prior to the study
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Miami Divison of Pulmonary and Critical Care Medicine
Miami, Florida, 33136
About this study
The objectives of the proposed study are to determine 1) the effect of a single dose of Roflumilast on airway blood flow (Qaw) (study period 1) and 2) the effect of long-term Roflumilast treatment on airway blood flow reactivity delta Qaw)(study period 2) in patients with stable COPD who use ICS regularly.
Read the detailed description
Participants will be enrolled in the study for three months There will be 6 study days (visits). The patients will be asked to come to the research laboratory in the morning of the study day. They will be instructed to abstain from ingesting alcoholic beverages or using PDE5 inhibitors the night before the study, and from consuming coffee or caffeinated drinks in the morning of the study day because of their potential acute cardiovascular actions. The patients will also be asked not to have a fatty breakfast on the study day to avoid potential effects of fat on the absorption of roflumilast.
The visits will be separated by at least 48 hours. Study period 1: The patients will be randomized into two arms: roflumilast or placebo. Qaw will be measured before and at 15, 30, 60, 120 and 240min in each arm (parallel design) Study period 2: Patients will be randomized to either roflumilast for 4 weeks or placebo for 4 weeks and airway blood flow reactivity will be measured at the end of the treatment period. The patients will then be taken off medication or placebo for 4 weeks and reassigned to the alternate treatment (roflumilast or placebo) for 4 weeks and airway blood flow reactivity will be measured after the this treatment period (cross-over design).
The treatments will be administered in a double-blind randomized design, using active roflumilast and identically appearing roflumilast placebo provided by Forest.
Visit 1
On this visit, a medical history will be obtained from the patients and they will undergo a physical examination and complete pulmonary function testing. If they meet entry criteria, Qaw will be measured before and 15 min after the inhalation of 180 µg albuterol using a spacer (ΔQaw). We have previously shown that vasodilation peaks between 5 and 30 min after inhaling this dose of albuterol in healthy non-smokers; in patients with COPD, who exhibit a vasodilatory response to inhaled albuterol, the peak effects also occur at the same time as in healthy subjects. Since all patients enrolled in the present study will be regular ICS users, we expect that all of them will have a vasodilator response to albuterol as previously shown.
Visit 2
On this day, Qaw will be measured before and at 15, 30, 60,120 and 240 min after the oral administration of either 500µg roflumilast or placebo, blinded to patient and investigator (acute roflumilast effects).
Visit 3
The patients will be given either 500µg roflumilast or placebo (alternate to treatment at visit 2) blinded to patient and investigator. One hour later, Qaw will be measured before and 15 min after the inhalation of 180µg albuterol using a spacer (ΔQaw). Pharmacokinetic studies have shown that the geometric mean plasma concentration of roflumilast after a 500µg dose peaks at one hour after oral drug administration.
The patients will then be randomized in a double blind fashion to either roflumilast 500 µg or placebo every morning before breakfast. They will be asked to return for a follow up visit 4 weeks later (visit 4).
Visit 4
The patients will not take their morning dose (roflumilast or placebo) on this day. Qaw will be measured before and 15 min after the inhalation of 180 µg albuterol using a spacer (ΔQaw). The treatment will be discontinued and the patients will be asked to return for visit 5 after a 4-week washout period.
Visit 5
The protocol of visit 4 will be repeated. The patients will then be started on the alternate treatment for 4 weeks: Those on roflumilast between visits 3 and 4 will now be placed on placebo, and those on placebo between visits 3 and 4 will be placed on roflumilast. The patients will be asked to return for a final visit (visit 6) 4 weeks later.
Visit 6
The protocol of visit 4 will be repeated. The patients will then undergo an exit exam and be discharged from the study
- Conditions
- COPD
- Being tested
- Roflumilast Placebo, Roflumilast
- Keywords
- COPD, airway blood flow
- 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.
Roflumilast PlaceboDrug
Placebo pill
RoflumilastDrug
Also called Daliresp
500 Ug ORAL TABLET
| Study group | Role | What they receive |
|---|---|---|
| SD placebo and MD roflumilast then MD placebo | Experimental | Participants will receive placebo (single dose) followed by a 4 week treatment with 500ug roflumilast daily, followed by a 4 week washout period, followed by a 4 week treatment with placebo daily. Receives: Drug: Roflumilast Placebo; Drug: Roflumilast |
| SD placebo and MD placebo then MD roflumilast | Experimental | Participants will receive placebo (single dose) followed by a 4 week treatment with placebo daily, followed by a 4 week washout period, followed by a 4 week treatment with 500ug roflumilast daily. Receives: Drug: Roflumilast Placebo; Drug: Roflumilast |
| SD roflumilast and MD placebo then MD roflumilast. | Experimental | Participants will receive 500ug roflumilast (single dose) followed by a 4 week treatment with placebo daily, followed by a 4 week washout period, followed by a 4 week treatment with 500ug roflumilast daily. Receives: Drug: Roflumilast Placebo; Drug: Roflumilast |
| SD roflumilast and MD roflumilast then MD placebo | Experimental | Participants will receive 500ug roflumilast (single dose) followed by a 4 week treatment with 500ug roflumilast daily, followed by a 4 week washout period, followed by a 4 week treatment with placebo daily Receives: Drug: Roflumilast Placebo; Drug: Roflumilast |
What is being measured
The primary outcome is the main question the study is designed to answer.
Airway Blood Flow Reactivity (Delta Qaw)
percentage of change on airway blood flow induced by albuterol.
Measured: Immediate or 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2014 (estimated)
- Study startFeb 2013
- Primary completionJul 2015
- Study completionJul 2015
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.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Collaborators
- Forest Laboratories
- 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
- NCT02097992
- Sponsor's protocol ID
- 20120591
- Other IDs
- DAL-IT-06
- Status last verified
- Oct 2017
- First submitted
- 13 Feb 2014
- Last updated
- 24 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Roflumilast on Airway Blood Flow as an Expression of Airway Inflammation in COPD
- ClinicalTrials.gov ID
- NCT02097992
- Acronym / sponsor ID
- 20120591
- Conditions
- COPD
- Keywords
- COPD, airway blood flow
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Collaborators
- Forest Laboratories
- Study start
- Feb 2013 (actual)
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 27 Mar 2014 (estimated)
- Results
- Posted 18 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objectives of the proposed study are to determine 1) the effect of a single dose of Roflumilast on airway blood flow (Qaw) (study period 1) and 2) the effect of long-term Roflumilast treatment on airway blood flow reactivity delta Qaw)(study period 2) in patients with stable COPD who use ICS regularly.
Detailed description
Participants will be enrolled in the study for three months There will be 6 study days (visits). The patients will be asked to come to the research laboratory in the morning of the study day. They will be instructed to abstain from ingesting alcoholic beverages or using PDE5 inhibitors the night before the study, and from consuming coffee or caffeinated drinks in the morning of the study day because of their potential acute cardiovascular actions. The patients will also be asked not to have a fatty breakfast on the study day to avoid potential effects of fat on the absorption of roflumilast.
The visits will be separated by at least 48 hours. Study period 1: The patients will be randomized into two arms: roflumilast or placebo. Qaw will be measured before and at 15, 30, 60, 120 and 240min in each arm (parallel design) Study period 2: Patients will be randomized to either roflumilast for 4 weeks or placebo for 4 weeks and airway blood flow reactivity will be measured at the end of the treatment period. The patients will then be taken off medication or placebo for 4 weeks and reassigned to the alternate treatment (roflumilast or placebo) for 4 weeks and airway blood flow reactivity will be measured after the this treatment period (cross-over design).
The treatments will be administered in a double-blind randomized design, using active roflumilast and identically appearing roflumilast placebo provided by Forest.
Visit 1
On this visit, a medical history will be obtained from the patients and they will undergo a physical examination and complete pulmonary function testing. If they meet entry criteria, Qaw will be measured before and 15 min after the inhalation of 180 µg albuterol using a spacer (ΔQaw). We have previously shown that vasodilation peaks between 5 and 30 min after inhaling this dose of albuterol in healthy non-smokers; in patients with COPD, who exhibit a vasodilatory response to inhaled albuterol, the peak effects also occur at the same time as in healthy subjects. Since all patients enrolled in the present study will be regular ICS users, we expect that all of them will have a vasodilator response to albuterol as previously shown.
Visit 2
On this day, Qaw will be measured before and at 15, 30, 60,120 and 240 min after the oral administration of either 500µg roflumilast or placebo, blinded to patient and investigator (acute roflumilast effects).
Visit 3
The patients will be given either 500µg roflumilast or placebo (alternate to treatment at visit 2) blinded to patient and investigator. One hour later, Qaw will be measured before and 15 min after the inhalation of 180µg albuterol using a spacer (ΔQaw). Pharmacokinetic studies have shown that the geometric mean plasma concentration of roflumilast after a 500µg dose peaks at one hour after oral drug administration.
The patients will then be randomized in a double blind fashion to either roflumilast 500 µg or placebo every morning before breakfast. They will be asked to return for a follow up visit 4 weeks later (visit 4).
Visit 4
The patients will not take their morning dose (roflumilast or placebo) on this day. Qaw will be measured before and 15 min after the inhalation of 180 µg albuterol using a spacer (ΔQaw). The treatment will be discontinued and the patients will be asked to return for visit 5 after a 4-week washout period.
Visit 5
The protocol of visit 4 will be repeated. The patients will then be started on the alternate treatment for 4 weeks: Those on roflumilast between visits 3 and 4 will now be placed on placebo, and those on placebo between visits 3 and 4 will be placed on roflumilast. The patients will be asked to return for a final visit (visit 6) 4 weeks later.
Visit 6
The protocol of visit 4 will be repeated. The patients will then undergo an exit exam and be discharged from the study
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| SD placebo and MD roflumilast then MD placebo | Experimental | Drug: Roflumilast Placebo, Drug: RoflumilastParticipants will receive placebo (single dose) followed by a 4 week treatment with 500ug roflumilast daily, followed by a 4 week washout period, followed by a 4 week treatment with placebo daily. |
| SD placebo and MD placebo then MD roflumilast | Experimental | Drug: Roflumilast Placebo, Drug: RoflumilastParticipants will receive placebo (single dose) followed by a 4 week treatment with placebo daily, followed by a 4 week washout period, followed by a 4 week treatment with 500ug roflumilast daily. |
| SD roflumilast and MD placebo then MD roflumilast. | Experimental | Drug: Roflumilast Placebo, Drug: RoflumilastParticipants will receive 500ug roflumilast (single dose) followed by a 4 week treatment with placebo daily, followed by a 4 week washout period, followed by a 4 week treatment with 500ug roflumilast daily. |
| SD roflumilast and MD roflumilast then MD placebo | Experimental | Drug: Roflumilast Placebo, Drug: RoflumilastParticipants will receive 500ug roflumilast (single dose) followed by a 4 week treatment with 500ug roflumilast daily, followed by a 4 week washout period, followed by a 4 week treatment with placebo daily |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Twenty-four patients with physician-diagnosed COPD (female and male, current smokers or ex-smokers) over the age of 45 years will be recruited for this study.
- The patients will have to have a smoking history of at least 10 pack-years, and they must have been using an ICS regularly for at least 4 weeks at the time of screening.
- Confirmation of the diagnosis of COPD will require the presence of persistent exertional dyspnea and a post-bronchodilator FEV1 of less than 80% of predicted and FEV1/FVC ratio less than 0.7 (GOLD stage ≥2). At entry into the study, the patients will have to be clinically stable; they will be allowed to remain on their regular COPD treatment regimen and use a LABA and/or LAMA until 24 hours before, and a SABA and/or short-acting muscarinic antagonist (SAMA) until 6 hours before coming to the laboratory. If using roflumilast, the subjects will have to discontinue it 4 weeks before entering into the study.-
Key exclusion criteria (7 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
- Use of supplemental oxygen that cannot be discontinued during the laboratory visit
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 |
|---|---|---|
| Roflumilast PlaceboPlacebo pill | Drug | SD placebo and MD placebo then MD roflumilast, SD placebo and MD roflumilast then MD placebo, SD roflumilast and MD placebo then MD roflumilast., SD roflumilast and MD roflumilast then MD placebo |
| RoflumilastAlso: Daliresp500 Ug ORAL TABLET | Drug | SD placebo and MD placebo then MD roflumilast, SD placebo and MD roflumilast then MD placebo, SD roflumilast and MD placebo then MD roflumilast., SD roflumilast and MD roflumilast then MD placebo |
Primary outcome
Airway Blood Flow Reactivity (Delta Qaw)
Time frame: Immediate or 4 weeks
percentage of change on airway blood flow induced by albuterol.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for COPD
Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
COPD, Smoking
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
COPD (Chronic Obstructive Pulmonary Disease), Sarcopenia in Elderly
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Study for GSK3862995B in Healthy Participants and Participants With Chronic Obstructive Pulmonary Disease
Pulmonary Disease, Chronic Obstructive
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 1/2 study testing Roflumilast 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 7 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 24 Nov 2017. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 18 Aug 2017). 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?
Airway Blood Flow Reactivity (Delta Qaw) (time frame: Immediate or 4 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 24 Nov 2017.