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

Sponsor

FLUIDDA nv (Industry)

Overall Status

Terminated

CT.gov ID

NCT02451540

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Radiation: HRCT scan Drug: Placebo of Roflumilast Drug: Roflumilast	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2015

Actual Primary Completion Date :

Aug 31, 2017

Actual Study Completion Date :

Aug 31, 2017

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Changes in Airway volume (iVaw) [At baseline and after 3 months of treatment]
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.
Changes in Airway resistance (iRaw) [At baseline and after 3 months of treatment]
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.
Changes in Lobe volumes (iVlobes) [At baseline and after 3 months of treatment]
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.
Changes in Air trapping [At baseline and after 3 months of treatment]
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.
Changes in Internal Lobar Airflow Distribution [At baseline and after 3 months of treatment]
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.
Low Attenuation or Emphysema Score [At baseline and after 3 months of treatment]
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.
Changes in Blood Vessel Density [At baseline and after 3 months of treatment]
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.
Changes in Airway Wall Thickness [3 months]
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.
Aerosol deposition concentrations [At baseline and after 3 months of treatment]
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.

Secondary Outcome Measures

Changes in Spirometry [At baseline and after 3 months of treatment]
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)
Changes in Body plethysmography [At baseline and after 3 months of treatment]
Body plethysmography is a composite outcome measure consisting of the following parameters: Residual Volume (RV) TLC FRC Airway resistance (Raw)
Changes in Diffusion capacity [At baseline and after 3 months of treatment]
Diffusion capacity is a composite outcome measure consisting of the following parameters: carbon monoxide transfer factor (TCO) Alveolar volume (VA)
Changes in 6MWT [At baseline and after 3 months of treatment]
Exercise capacity: distance walked in 6 minutes (m), oxygen saturation measurement will be performed during the test
Changes in Patient Related Outcome (PRO) [At baseline and after 3 months of treatment]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)