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

Study Overview
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Brief Summary
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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.

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

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Radiation: HRCT scan
* Drug: Placebo of Roflumilast
* Drug: Roflumilast


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Roflumilast<br>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<br>* HRCT scan of thorax, at baseline and after 3 months<br>Drug: Roflumilast<br>* Roflumilast, once a day in the morning during 3 months<br>* Other names: Daxas;|
| Placebo Comparator: Placebo<br>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<br>* HRCT scan of thorax, at baseline and after 3 months<br>Drug: Placebo of Roflumilast<br>* Placebo, once a day in the morning during 3 months<br>* Other names: Placebo;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Roflumilast, Pulmonary Disease, Chronic Obstructive, dynamics hyperinflation, Computed Tomography scan, CT scan, Functional Respiratory Imaging, FRI, PRO