Ignite Creation Date:
2025-12-24 @ 3:55 PM
Ignite Modification Date:
2025-12-24 @ 3:55 PM
Study NCT ID:
NCT02097992
Status:
COMPLETED
Last Update Posted:
2017-11-24
First Post:
2014-02-13
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Effect of Roflumilast on Airway Blood Flow as an Expression of Airway Inflammation in COPD
Sponsor:
University of Miami
Organization:
Study Overview
Official Title:
Effect of Roflumilast on Airway Blood Flow as an Expression of Airway Inflammation in COPD
Status:
COMPLETED
Status Verified Date:
2017-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| DAL-IT-06 | OTHER_GRANT | FOREST | View |