The Effectiveness of Roflumilast in Improving Mucociliary Clearance in Patients With COPD and Chronic Bronchitis

NCT ID: NCT03073798

Last Updated: 2017-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-18
• Study Completion Date: 2015-05-14

Brief Summary

Specific Aim: To determine the effectiveness of Roflumilast in improving i) whole right lung and ii) peripheral right lung mucociliary clearance (MCC) in patients with COPD and chronic bronchitis.

Hypothesis: Roflumilast increases mucociliary clearance in patients with chronic bronchitis.

Study Design: This will be a double-blinded, cross-over randomized controlled trial with 1:1 randomization of 20 individuals with chronic bronchitis. Subjects will undergo baseline MCC then will be randomized to either roflumilast or placebo x 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. MCC will be conducted at baseline and at the end of each 4 week medication phase.

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.

Conditions

COPD; Chronic Bronchitis; Emphysema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Medication

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.

Group Type: ACTIVE_COMPARATOR

Roflumilast

Intervention Type: 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

Placebo

Intervention Type: DRUG

500 mcg of placebo is used

Placebo

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

Group Type: PLACEBO_COMPARATOR

Roflumilast

Intervention Type: 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

Placebo

Intervention Type: DRUG

500 mcg of placebo is used

Interventions

Roflumilast

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

Intervention Type: DRUG

Placebo

500 mcg of placebo is used

Intervention Type: DRUG

Other Intervention Names

Daliresp; Sugar Pill

Eligibility Criteria

Inclusion Criteria

• Physician diagnosis of COPD
• Forced Expiratory Volume in 1 second (FEV1) / Forced Vital Capacity (FVC) ≤70%
• FEV1 (% predicted) ≥40 % AND ≤ 70%,
• Tobacco exposure ≥ 10 pack-years,
• Chronic cough and sputum production
• At least one COPD exacerbation requiring systemic glucocorticosteroids or treatment in hospital, or both, in the previous year
• Not suffering from any concomitant disease that might interfere with study procedures or evaluations.

Exclusion Criteria

• COPD exacerbation indicated by a treatment with systemic glucocorticosteroids and/or antibiotics not stopped at least 4 weeks prior to the baseline visit V0
• Lower respiratory tract infection not resolved 4 weeks prior to the baseline visit V0
• Diagnosis of asthma and/or other relevant lung disease (e.g. history of bronchiectasis, cystic fibrosis, bronchiolitis, lung resection, lung cancer, interstitial lung disease [e.g. fibrosis, silicosis, sarcoidosis], and active tuberculosis
• Known alpha-1-antitrypsin deficiency
• Known infection with HIV and/or active hepatitis
• Pregnancy or women of childbearing potential not using or willing to continue using a medically reliable method of contraception for the entire study period
• Suspected hypersensitivity to the study medication (roflumilast).
• Use of mucolytics within the last 4 weeks.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nadia Hansel, MD MPH

Role: PRINCIPAL_INVESTIGATOR

Jonhs Hopkins University

Beth Laube, PhD

Role: PRINCIPAL_INVESTIGATOR

Jonhs Hopkins University

Other Identifiers

NA_00078710

Identifier Type: -

Identifier Source: org_study_id