Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Pulmonary Function, COPD, 129-Xenon, Magnetic Resonance Imaging
Brief summary
The goal of this study is to study how 12-weeks daily (and optional 48-weeks) single inhaler triple therapy (fluticasone furoate (FF)-an inhaled corticosteroid; umeclidinium (UMEC)-a long-acting muscarinic antagonist; vilanterol (VI)-a long-acting β2-adrenergic agonist) works to treat adults with COPD. The investigators will compare the effects of this medication on adults with COPD who are at low risk of a flare-up and adults with COPD who are at high risk of a flare-up. The main questions it aims to answer are: * Does FF/UMEC/VI improve ventilation defect percent as measured on 129-Xenon MRI in adults with moderate-severe COPD * Evaluate the relationships between the ventilation defect percent and lung function test results Participants will: * Take the inhaler FF/UMEC/VI once daily for 12-weeks (optional 48-weeks) * visit Robarts 2 times (with optional 3rd visit) for tests and imaging
Detailed description
This study will evaluate 60 COPD patients age 50-85 (equal numbers males and females) with persistent, moderate-severe dyspnea, poor health status and either: 1) low risk of exacerbation (n=30) or moderate-high risk of exacerbation (n=30). Two visits at baseline and 12-weeks are proposed with an optional visit at 48-weeks to assess longitudinal effects of therapy. At all study visits participants will have vital signs recorded and undergo pre- and post-bronchodilator spirometry, plethysmography, oscillometry, pre-bronchodilator forced exhaled nitric oxide (FeNO) and post-bronchodilator diffusing capacity of the lungs for carbon monoxide (DLco). Participants will undergo pre- and post-bronchodilator 129-Xe MRI and post-bronchodilator chest computed tomography (CT). Participants will complete St. George's Respiratory Questionnaire (SGRQ), Modified Medical Research Council (mMRC), COPD Assessment Test (CAT), Borg rating of perceived exertion questionnaire will be completed before and after the six-minute walk test (6MWT). Participants will have a blood draw for complete blood count (CBC).
Interventions
DRUGfluticasone furoate(FF)/umeclidinium (UMEC)/vilanterol(VI) (100/62.5/25) mcg
The investigational drug is a single Ellipta inhaler containing 100 ug fluticasone furoate(inhaled corticosteroid), 62.5 ug umeclidinium(long-acting muscarinic antagonist) and 25 ug vilanterol(long-acting β2-adrenergic agonist). The drug is delivered in an Ellipta inhaler in a single dose once daily.
Sponsors
Western University, Canada
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
single arm, open-label study
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* patient understands study procedures and is willing to participate in the study as indicated by the patient's signature * provision of written, informed consent prior to any study specific procedures * males and females 50-85 years of age * stable COPD, currently on dual therapy LAMA/LABA or ICS/LABA or initial maintenance therapy for at least 3 months * mMRC score ≥2 and/or CAT score ≥10 * Low risk subgroup: participant has experienced ≤1 exacerbation in the past year and no hospitalizations for COPD High risk subgroup: participant has experienced ≥2 exacerbations in the past year * Female of childbearing potential (after menarche) must ensure that they are using an effective form of birth control for at least 2 months prior to each imaging visit. Examples of effective birth control include: 1. True sexual abstinence 2. A vasectomized sexual partner 3. Implanon® 4. Female sterilization by tubal occlusion 5. Effective intrauterine device (IUD)/levonogestrel intrauterine system (IUS) 6. Depo-Provera™ injections 7. Oral contraceptive 8. Evra Patch™ 9. Nuvaring™ * Female permanently sterile due to: 1) documented hysterectomy, 2) documented bilateral salpingectomy, and 3) documented bilateral oophorectomy * Postmenopausal female: defined as female with no menses for 12 months without an alternative medical cause * Females of childbearing potential (after menarche) must agree to use a highly effective form of birth control, as defined above, from enrollment, throughout the study duration, and 8 weeks after last dose of study drug, with negative urine pregnancy test taken within 24 hr of any planned CT examination at Visit-1 through Visit 3 * Male participants who are sexually active with a woman who can still have children, must agree to use a double barrier method of contraception (male condom with diaphragm or male condom with cervical cap) from the first dose of the study drug until 8 weeks after last dose
Exclusion criteria
* Patient has an implanted mechanically, electrically, or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants) (at the discretion of the MRI Technologist) * In the investigator's opinion, participant suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI or CT, such as severe claustrophobia * Participants who are pregnant, breastfeeding or have a positive pregnancy test at initial screening visit * Participant is unable to perform spirometry or plethysmography maneuvers * Participant is unable to perform MRI and CT breath-hold maneuvers * Participant has an unstable cardiovascular, gastro-intestinal, hepatic, renal, neurologic, metabolic or psychiatric disease * Participation in any clinical trial of an investigational agent or procedure within three months prior to screening or during the study * Known history of allergy or reaction to the study drug formulation * Participant has a blood pressure of \>150 mmHg systolic or \>95 mmHg diastolic on more than 2 measurements done \>5 minutes apart at Visit-1 * Participants with a recently (\<2 months) documented diagnosis of asthma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure the effect of FF/UMEC/VI therapy on VDP | 12-weeks and optional 48-weeks | Measured using 129-xenon MRI ventilation defect percent |
| Measure the effect of FF/UMEC/VI on FEV1 | at 12-weeks and optional 48-weeks | Measured by the forced expiratory volume at 1 second |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the relationship between MRI VDP and lung function | 12-weeks and optional 48-weeks | measured using MRI ventilation defect percent and forced expiratory volume at 1 second |
| Evaluate the relationship between MRI VDP and SGRQ score | 12-weeks and optional 48-weeks | measured using 129-xenon MRI ventilation defect percent and St. George's Respiratory Questionnaire score |
| Evaluate the relationship between MRI VDP and CAT score | 12-weeks and optional 48-weeks | Measured using 129-xenon MRI ventilation defect percent and COPD Assessment Test score |
| Evaluate the relationship between MRI VDP and mMRC score | 12-weeks and optional 48-weeks | Measured using 129-xenon MRI ventilation defect percent and modified Medical Research Council questionnaire score |
| Evaluate the relationship between MRI VDP and 6MWD | 12-weeks and optional 48-weeks | Measured using 129-xenon MRI ventilation defect percent and six-minute walk distance. |
| Evaluate and compare potential differences in MRI VDP response among patients with low- and high-risk of exacerbation. | 12-weeks and optional 48-weeks | Measured using 129-xenon MRI ventilation defect percent and comparing exacerbation rates across patients with low- and high-risk of exacerbation. |
| Evaluate the relationship between MRI VDP and blood inflammatory markers | 12-weeks and optional 48-weeks | Measured using 129-xenon MRI ventilation defect percent and blood eosinophil count |
| Evaluate the relationship between MRI VDP and CT measurements | 12-weeks and optional 48-weeks | Measured using 129-xenon MRI ventilation defect percent and CT mucus-score |
| Evaluate change in VDP as a predictor of annualized exacerbation rate | 12-weeks and optional 48-weeks | Measured using change in 129-xenon MRI ventilation defect percent with annualized exacerbation rate as reported by the participant |
| Evaluate the relationship between MRI VDP and lung volume | 12-weeks and optional 48-weeks | Measured using MRI ventilation defect percent and forced vital capacity |
Countries
Canada
Contacts
CONTACTGrace E Parraga, PhD
CONTACTAngela Wilson, RRT
PRINCIPAL_INVESTIGATORGrace Parraga, PhD
Robarts Research Institute, The University of Western Ontario
Outcome results
None listed