Chronic obstructive pulmonary disease (COPD) Respiratory
Conditions
Interventions
Intervention arm:
Patients randomised to the intervention arm will receive Trixeo Aerosphere (formoterol fumarate/glycopyrronium/budesonide - 5 micrograms/7.2 micrograms/160 micrograms pressurised inh
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Age
18 Years to 110 Years
Inclusion criteria
Inclusion criteria: 1. Clinical diagnosis of COPD 2. Not on regular treatment with inhaled corticosteroids (ICS) 3. Over 18 years of age 4. Symptomatic disease (COPD Assessment Test [CAT] score of =10) 5. FEV1 measured by spirometry <80% predicted 6. Able to demonstrate adequate inhaler technique 7. Willing to take study medications as instructed
Exclusion criteria
Exclusion criteria: 1. Subjects unable to give informed consent form 2. Pregnancy or breastfeeding 3. Patients on regular treatment with inhaled corticosteroids (ICS) 4. Very severe disease FEV1<30% 5. Patients with more than two moderate exacerbations, or one severe (requiring hospitalization) within the last year 6. Patients with significant cardiac comorbidities, arrhythmias and/or on antiplatelet treatment 7. Patients with acute worsening of COPD in the 6 weeks prior to screening resulting in treatment with oral corticosteroids or antibiotics 8. Patients with asthma, other significant comorbidities including cancer, neurological, hepatic, endocrine, renal (creatinine clearance <30 ml/min) disorders, narrow-angle glaucoma or prostatic hypertrophy 9. Patients who are taking part in interventional clinical trials 10. Patients with known hypersensitivity to budesonide, glycopyrronium or formoterol 11. For women of childbearing potential only – currently pregnant, breastfeeding, or planned pregnancy during the study or not using acceptable contraception, as judged by the investigator 12. Patients with allergy to latex 13. As a result of the medical interview, physical examination or screening investigations, the Physician Responsible considers the volunteer unfit for the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Degree of senescence in endothelial progenitors isolated from blood (endothelial colony forming cells: ECFC), measured by markers of senescence and DNA damage response, isolated from COPD patients at baseline and 12 weeks post-treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Measured at baseline and 12 weeks post-treatment: 1. Endothelial function assessed using the EndoPAT device 2. Quality of life assessed using the COPD assessment test 3. Mean arterial pressure calculated from systolic and diastolic blood pressure (BP) readings 4. Prediction algorithms for CVD (Framingham risk score risk prediction model and QRISK3- risk prediction model) 5. Blood eosinophils measured via the patients’ blood sample 6. Blood cardiovascular markers (high-sensitivity C-reactive protein, brain-natriuretic-peptide, troponin, fibrinogen, activation of the RAS system [renin to aldosterone ratio]) measured via the patients’ blood sample 7. Proteomic analysis of ECFC, serum/plasma for studying the senescence-associated secretome, isolated from the patients’ blood sample 8. miR-126-3p and other miRNA dysregulation in ECFC, isolated from the patients’ blood sample 9. Markers of senescence and DDR in treated ECFC ex-vivo in 2D culture models, isolated from the patients’ blood sample 10. Permeability and markers of senescence in treated microvessels (3D culture models) using ECFC, isolated from the patients’ blood sample 11. Spirometry: forced expiratory spirometry maneuvers for the derivation of FEV1 and FVC will be assessed using a spirometer that meets or exceeds the minimum performance recommendations of the ATS. Outcomes will be FEV1, FVC, FEV1/FVC 12. Body mass index (BMI), calculated as weight in kilos divided by height in meters squared. Height measured at the start of the study will be used for both measures. Electronic scales will be used to measure weight. 13. Breathlessness assessed using the extended version of the Medical Research Council Dyspnoea Scale (eMRC) 14. Quality of life measured using St George’s Respiratory Questionnaire (SGRQ) 15. Exacerbation history: number of exacerbations in the last year, number of times admitted to hospital with exacerbation the last year and number of times admitted to hospital with exacerbations overall will | — |
Countries
England, United Kingdom
Contacts
Public ContactKoralia Paschalaki
Outcome results
None listed