The Effectiveness of Roflumilast in Improving Mucociliary... | NCT03073798

NCT03073798

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Detailed Description

The purpose of this study is to investigate how well Roflumilast improves mucociliary clearance in people with chronic bronchitis. Several studies show that roflumilast may modulate (change) mucociliary function. This study is designed to determine if these favorable effects lead to improved mucociliary clearance (MCC) in people with chronic bronchitis, thereby, reducing the potential for acute infections and hospitalizations. Daliresp® (roflumilast) is a drug currently marketed (approved by the U.S. Food and Drug Administration (FDA) for use in humans) in the U.S. and is indicated (used) for treatment of people with severe COPD to treat the symptoms of cough and excess mucous linked to chronic bronchitis. Roflumilast is used to reduce the risk (chance) of COPD exacerbations (increase in symptoms such as cough, mucus secretions, and shortness of breath, that can be life threatening and reduces the ability to breathe) linked to chronic bronchitis (swelling of the airways in the lungs). Roflumilast is FDA approved to decrease the number of flare-ups of chronic obstructive pulmonary disease (COPD) in patients with severe COPD with chronic bronchitis and a history of flare-ups. The exact way Roflumilast does this is not known. Although Roflumilast is an FDA approved drug, in this study the drug is not being used for its FDA-approved indication.

If you agree to be in this study, you will receive no new COPD treatment other than the drugs provided for the study. You will also be given a tablet to take once a day, which will be placebo for at least part of the study. A placebo is a substance that looks like the study drug but that contains no active ingredients.

The study is a double-blind study. Double-blind means that neither you nor the study doctor will know which study regimen (roflumilast or placebo) you are receiving throughout the study. However, this information can be made available if medically necessary and as determined by the participant's study. You will undergo baseline mucociliary Clearance (MCC) Measurements then will be randomized (by chance, like the flip of a coin) to receive either roflumilast or placebo for 4 weeks, then there will be a 4 week wash-out phase, and a second 4 week period of roflumilast/placebo depending on initial randomization. Mucociliary Clearance (MCC) Measurements will be conducted at the beginning and at the end of each 4 week study regimen phase. You will be in the study for about 12 weeks and there will be up to 12 visits. At baseline, and prior to each MCC Procedure, you will have health assessments which may include Physical Examination, Health and Demographic Interview, Exhaled Carbon Monoxide (eCO) Testing, Spirometry (Breathing Test), Expectorated Sputum Collection, Pregnancy Testing and Mucociliary Clearance (MCC) Measurements.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Medication	Active Comparator	Roflumilast. 500 mcg of Roflumilast daily for 4 weeks, then there will be a 4 week wash-out phase (no medication) and a second 4 week period of placebo.	Drug: Roflumilast Drug: Placebo
Placebo	Placebo Comparator	Placebo. 500 mcg of Placebo daily for 4 weeks, then there will be a 4 week wash-out phase (no medication) and a second 4 week period of Roflumilast	Drug: Roflumilast Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Roflumilast	Drug	500 mcg of Roflumilast which is a prescription medicine used in adults with severe COPD to decrease the number of flare-ups or the worsening of COPD symptoms	Medication

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Difference in Mucociliary Clearance (MCC) Between Visit 1A and Visit 2A	Measurements of MCC (Mucociliary clearance) will be obtained using a large-field-of-view 2D gamma camera (Siemens Orbiter) following inhalation of a radioaerosol containing a gamma emitting isotope 99mtechnetium (99mTc)-sulfur-colloid. The total exposure to radiation from procedures associated with the MCC studies is similar to that of a chest x-ray and is much less than the 0.3 rem that the average person in the United States gets each year from natural sources like the sun, outer space, air, food, and soil. After inhaling (0 time point) an aerosol generated from a saline solution containing the radioisotope 99mtechnetium (99mTc)-sulfur-colloid (radioaerosol), subjects will sit with their back to a gamma camera. The gamma camera will acquire an image of where the isotopic marker initially deposits in the right lung at time 0 and how much remains in the lungs at the specified time point and will be measured in change of %/min from 0 min time point.	Change from 0 to 30 minutes
Difference in Mucociliary Clearance (MCC) Between Visit 1A and Visit 2A	Measurements of MCC (Mucociliary clearance) will be obtained using a large-field-of-view 2D gamma camera (Siemens Orbiter) following inhalation of a radioaerosol containing a gamma emitting isotope 99mtechnetium (99mTc)-sulfur-colloid. The total exposure to radiation from procedures associated with the MCC studies is similar to that of a chest x-ray and is much less than the 0.3 rem that the average person in the United States gets each year from natural sources like the sun, outer space, air, food, and soil. After inhaling (0 time point) an aerosol generated from a saline solution containing the radioisotope 99mtechnetium (99mTc)-sulfur-colloid (radioaerosol), subjects will sit with their back to a gamma camera. The gamma camera will acquire an image of where the isotopic marker initially deposits in the right lung at time 0 and how much remains in the lungs at the specified time point and will be measured in change of %/min from 0 min time point.	Change from 0 to 60 minutes
Difference in Mucociliary Clearance (MCC) Between Visit 1A and Visit 2A	Measurements of MCC (Mucociliary clearance) will be obtained using a large-field-of-view 2D gamma camera (Siemens Orbiter) following inhalation of a radioaerosol containing a gamma emitting isotope 99mtechnetium (99mTc)-sulfur-colloid. The total exposure to radiation from procedures associated with the MCC studies is similar to that of a chest x-ray and is much less than the 0.3 rem that the average person in the United States gets each year from natural sources like the sun, outer space, air, food, and soil. After inhaling (0 time point) an aerosol generated from a saline solution containing the radioisotope 99mtechnetium (99mTc)-sulfur-colloid (radioaerosol), subjects will sit with their back to a gamma camera. The gamma camera will acquire an image of where the isotopic marker initially deposits in the right lung at time 0 and how much remains in the lungs at the specified time point and will be measured in change of %/min from 0 min time point.

Eligibility Module

Name	Affiliation	Role
Nadia Hansel, MD MPH	Jonhs Hopkins University	Principal Investigator
Beth Laube, PhD	Jonhs Hopkins University	Principal Investigator

ID	Title	Description
FG000	All Participants	Subjects underwent baseline MCC, then first received Roflumilast 500 mcg daily for 4 weeks. After a washout period of 4 weeks, they then received Placebo 500 mcg for an additional 4 weeks.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	All Participants	Roflumilast. 500 mcg of Roflumilast daily for 4 weeks, then there will be a 4 week wash-out phase (no medication) and a second 4 week period of placebo. Roflumilast: 500 mcg of Roflumilast which is a prescription medicine used in adults with severe Chronic Obstructive Pulmonary Disease (COPD) to decrease the number of flare-ups or the worsening of COPD symptoms Placebo: 500 mcg of placebo is used

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	Difference in Mucociliary Clearance (MCC) Between Visit 1A and Visit 2A	Measurements of MCC (Mucociliary clearance) will be obtained using a large-field-of-view 2D gamma camera (Siemens Orbiter) following inhalation of a radioaerosol containing a gamma emitting isotope 99mtechnetium (99mTc)-sulfur-colloid. The total exposure to radiation from procedures associated with the MCC studies is similar to that of a chest x-ray and is much less than the 0.3 rem that the average person in the United States gets each year from natural sources like the sun, outer space, air, food, and soil. After inhaling (0 time point) an aerosol generated from a saline solution containing the radioisotope 99mtechnetium (99mTc)-sulfur-colloid (radioaerosol), subjects will sit with their back to a gamma camera. The gamma camera will acquire an image of where the isotopic marker initially deposits in the right lung at time 0 and how much remains in the lungs at the specified time point and will be measured in change of %/min from 0 min time point.	Data was not collected for all participants in this outcome measure due to lack of follow-up, patient withdrawal from the study, and an adverse event.	Posted		Mean	Standard Deviation	percentage difference of MCC		Change from 0 to 30 minutes

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	All Participants	Subjects underwent baseline MCC, then first received Roflumilast 500 mcg daily for 4 weeks. After a washout period of 4 weeks, they then received Placebo 500 mcg for an additional 4 weeks. MCC was conducted at baseline and at the end of each 4 week medication phase.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Pulmonary Exacerbation	Respiratory, thoracic and mediastinal disorders		Non-systematic Assessment	One participant had a pulmonary exacerbation prior to drug administration.

ID	Term
D029424	Pulmonary Disease, Chronic Obstructive
D029481	Bronchitis, Chronic
D004646	Emphysema
D008171	Lung Diseases
D004417	Dyspnea
D012907	Smoking

ID	Term
D008173	Lung Diseases, Obstructive
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes

ID	Title	Description
OG000	All Roflumilast MCC	Taking into account the washout period and crossover design of this study, we are presenting the results to reflect all of the MCC studies done while the participants were on roflumilast.
OG001	All Placebo MCC	Taking into account the washout period and crossover design of this study, we are presenting the results to reflect all of the MCC studies done while the participants were on placebo.

ID	Term
C424423	Roflumilast
D000073893	Sugars