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

NCT03073798 | Completed Phase 4 Results DMC

• 1 other identifier: NA_00078710
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

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.

Conditions

COPD; Chronic Bronchitis; Emphysema

Keywords

Lung Disease; Breathing Difficulty; Smoking; Mucociliary

Outcome Measures

Primary Outcomes (4)

• 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.

  Change from 0 to 90 minutes

• Difference in Mucociliary Clearance (MCC) Between Visit 1B and Visit 2B

  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 min to 24 hours

Study Arms (2)

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

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

Also known as: Daliresp

Medication; Placebo

Placebo DRUG

500 mcg of placebo is used

Also known as: Sugar Pill

Medication; Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Bronchitis, Chronic; Emphysema; Lung Diseases; Dyspnea; Smoking

Interventions

Roflumilast; Sugars

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Carbohydrates

Results Point of Contact

• Title: Nadia N Hansel, MD MPH
• Organization: Johns Hopkins University

nhansel@jhmi.edu

410-550-2935

Study Officials

• Nadia Hansel, MD MPH

  Jonhs Hopkins University

  PRINCIPAL INVESTIGATOR

• Beth Laube, PhD

  Jonhs Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2017
• First Posted: March 8, 2017
• Study Start: March 18, 2013
• Primary Completion: May 14, 2015
• Study Completion: May 14, 2015
• Last Updated: July 27, 2017
• Results First Posted: July 27, 2017

Record last verified: 2017-06