Evaluation of the Effect of Roflumilast in Hyperinflated COPD Patients Using Functional Respiratory Imaging

Placebo Controlled Study to Assess the Effect of Roflumilast in Hyperinflated COPD Patients in Addition to LABA/LAMA Therapy Using Functional Respiratory Imaging.

In this study the efficacy of Roflumilast in addition to LAMA/LABA therapy will be assessed using Functional Respiratory Imaging.

In total 40 Chronic obstructive pulmonary disease (COPD) patients, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages C and D, who are stable on LABA/LAMA therapy and who are prone to dynamics hyperinflation will be included in this study. To indicate the susceptibility to dynamics hyperinflation patients should have a baseline Borg Fatigue score after the 6-minute walk test (6MWT) above 4.

The patients will be randomized in such a way that 1 out of 2 patients will receive placebo and 1 the active component.

Image parameters will be assessed and the correlation with lung function and health related quality of life will be checked before and after treatment.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Radiation: HRCT scan; Drug: Roflumilast; Drug: Placebo of Roflumilast

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerp
    • Edegem, Antwerp, Belgium, 2650
      • University Hospital of Antwerp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patient ≥ 30 years old
• Written informed consent obtained
• Patient with Body mass index (BMI) ≥ 20
• Female patient of childbearing potential who confirm that a contraception method was used at least 14 days before visit 1 and will continue to use a contraception method during the study
• COPD patient with GOLD stages C and D
• Patient with a Borg Fatigue score after the 6MWT on screening above 4 to indicate the susceptibility to dynamics hyperinflation
• Patient with smoking history of at least 10 pack-years
• Patient takes a combination therapy of LABA/ LAMA at least 6 weeks before visit 1
• Patient must be able to understand and complete the protocol requirements, instructions, questionnaires and protocol-stated restrictions

Exclusion Criteria:

• Pregnant or lactating females
• Patient with severe immunological diseases and/ or severe acute infectious diseases
• Patient with heart failure as documented in the medical history or as defined by the investigator during the physical examination performed at visit 1
• Patient with diagnosis of cancer (except basal cell carcinoma)
• Patient with a history of depression associated with suicidal ideation or behaviour
• Patient with moderate or severe hepatic impairment.
• Patient with lactose intolerance
• Patient is unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study.
• Patient who received inhalation corticosteroids (ICS) within the last 6 weeks prior to the screening visit
• Patient who received any investigational new drug within the last 4 weeks prior to the screening visit or twice the duration of the biological effect of any drug (whichever is longer)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Roflumilast; Patient will take Roflumilast (500 micrograms) once a day for 3 months. A HRCT scan will be taken at baseline and after 3 months of treatment	Radiation: HRCT scan; HRCT scan of thorax, at baseline and after 3 months; Drug: Roflumilast; Roflumilast, once a day in the morning during 3 months; Other Names: Daxas
Placebo Comparator: Placebo; Patient will take the Placebo of Roflumilast once a day for 3 months. A HRCT scan will be taken at baseline and after 3 months.	Radiation: HRCT scan; HRCT scan of thorax, at baseline and after 3 months; Drug: Placebo of Roflumilast; Placebo, once a day in the morning during 3 months; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Airway volume (iVaw)	By using Functional Respiratory Imaging the efficacy of Roflumilast in addition to long-acting muscarinic antagonist (LAMA)/ long acting β2-agonist (LABA) therapy will be assessed.	At baseline and after 3 months of treatment
Changes in Airway resistance (iRaw)	By using Functional Respiratory Imaging the efficacy of Roflumilast in addition to long-acting muscarinic antagonist (LAMA)/ long acting β2-agonist (LABA) therapy will be assessed.	At baseline and after 3 months of treatment
Changes in Lobe volumes (iVlobes)	By using Functional Respiratory Imaging the efficacy of Roflumilast in addition to long-acting muscarinic antagonist (LAMA)/ long acting β2-agonist (LABA) therapy will be assessed.	At baseline and after 3 months of treatment
Changes in Air trapping	By using Functional Respiratory Imaging the efficacy of Roflumilast in addition to long-acting muscarinic antagonist (LAMA)/ long acting β2-agonist (LABA) therapy will be assessed.	At baseline and after 3 months of treatment
Changes in Internal Lobar Airflow Distribution	By using Functional Respiratory Imaging the efficacy of Roflumilast in addition to long-acting muscarinic antagonist (LAMA)/ long acting β2-agonist (LABA) therapy will be assessed.	At baseline and after 3 months of treatment
Low Attenuation or Emphysema Score	By using Functional Respiratory Imaging the efficacy of Roflumilast in addition to long-acting muscarinic antagonist (LAMA)/ long acting β2-agonist (LABA) therapy will be assessed.	At baseline and after 3 months of treatment
Changes in Blood Vessel Density	By using Functional Respiratory Imaging the efficacy of Roflumilast in addition to long-acting muscarinic antagonist (LAMA)/ long acting β2-agonist (LABA) therapy will be assessed.	At baseline and after 3 months of treatment
Changes in Airway Wall Thickness	By using Functional Respiratory Imaging the efficacy of Roflumilast in addition to long-acting muscarinic antagonist (LAMA)/ long acting β2-agonist (LABA) therapy will be assessed.	3 months
Aerosol deposition concentrations	By using Functional Respiratory Imaging the efficacy of Roflumilast in addition to long-acting muscarinic antagonist (LAMA)/ long acting β2-agonist (LABA) therapy will be assessed.	At baseline and after 3 months of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Spirometry	Spirometry is a composite outcome measure consisting of the following parameters: FEV1; Peak Expiratory Flow (PEF); Forced Vital Capacity (FVC); Maximum Expiratory Flow at 50% of FVC (MEF 50); Maximum Expiratory Flow at 25% of FVC (MEF 25)	At baseline and after 3 months of treatment
Changes in Body plethysmography	Body plethysmography is a composite outcome measure consisting of the following parameters: Residual Volume (RV); TLC; FRC; Airway resistance (Raw)	At baseline and after 3 months of treatment
Changes in Diffusion capacity	Diffusion capacity is a composite outcome measure consisting of the following parameters: carbon monoxide transfer factor (TCO); Alveolar volume (VA)	At baseline and after 3 months of treatment
Changes in 6MWT	Exercise capacity: distance walked in 6 minutes (m), oxygen saturation measurement will be performed during the test	At baseline and after 3 months of treatment
Changes in Patient Related Outcome (PRO)	Patient Related Outcome is a composite outcome measure consisting of the following questionnaires: Borg CR10 Scale: measure of the present dyspnea and leg fatigue before and after exercise; COPD assessment test (CAT): measure of the impact of COPD on your life; Saint George's Respiratory Questionnaire (SGRQ): measure health related quality of life and comfort	At baseline and after 3 months of treatment

Collaborators and Investigators

• Sponsor: FLUIDDA nv

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): August 31, 2017
• Study Completion (Actual): August 31, 2017

Study Registration Dates

• First Submitted: May 7, 2015
• First Submitted That Met QC Criteria: May 19, 2015
• First Posted (Estimate): May 22, 2015

Study Record Updates

• Last Update Posted (Actual): March 21, 2018
• Last Update Submitted That Met QC Criteria: March 19, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: PRO; Pulmonary Disease, Chronic Obstructive; CT scan; Roflumilast; Functional Respiratory Imaging; FRI; Computed Tomography scan; dynamics hyperinflation
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Chronic Disease
• Other Study ID Numbers: FLUI-2014-134