Measuring response to inhaled asthma therapy using pulmonary imaging
| ISRCTN | ISRCTN18210817 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18210817 |
| ClinicalTrials.gov number | NCT04651777 |
| Secondary identifying numbers | Unique Protocol ID: ROB0046 |
- Submission date
- 15/03/2024
- Registration date
- 15/03/2024
- Last edited
- 18/03/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English Summary
Background and study aims
The purpose of this study is to evaluate the effectiveness of treatment with triple therapy (an inhaler that contains three types of asthma medications) on participants with poorly controlled asthma. The triple therapy medication contains fluticasone furoate, an inhaled corticosteroid (ICS) which reduces inflammation in the lungs; umeclidinium (UMEC), a long-acting muscarinic antagonist (LAMA), a medication which helps open up the airways; and vilanterol (VI), a long-acting beta2-adrenergic agonist (LABA) which also helps open up airways, delivered in a single daily inhalation via an Ellipta inhaler. The Investigators will evaluate lung structure and function using magnetic resonance imaging (MRI). Participants will inhale xenon gas before an MRI image of their lungs is taken. Using a special technique xenon is visible in MRI images, so this lets us see how air spreads in the lungs. In healthy lungs, the gas fills the lungs evenly, but in unhealthy lungs, the gas may fill the lungs unevenly and they will appear patchy. The patchy areas are called ventilation defects. A CT of the chest will be done to assess the structure of the lungs. The Investigators will also be using lung function testing and questionnaires to compare them to MRI ventilation defect measurements.
Who can participate?
Males and females aged 18-75 years with a clinical diagnosis of eosinophilic asthma
What does the study involve?
Vital signs will be recorded at the beginning of the visit. Lung tests and an MRI scan will be performed before and after inhaling four puffs (100 mcg each) of a bronchodilator and quietly resting for 15 minutes. Questionnaires will be completed after post-bronchodilator assessments are completed. For Visit 3, participants who choose to attend an in-person visit are to withhold their medication as described and the process for Visits 1, 2 and 4 will be followed. Participants who choose a phone call Visit 3 will be asked a series of questions regarding their breathing, asthma control and general health and they will complete questionnaires. For all participants, Visit 5 will entail a phone call check-in for adverse events. CT will be acquired at Visit 2, whilst MRI will be acquired on Visits 2, 4 and for those who prefer an in-person visit, on Visit 3.
What are the possible benefits and risks of participating?
Participants with poorly controlled disease may benefit from the treatment, including reduced asthma exacerbations, reduced use of oral corticosteroids (OCS) and improved lung function. The safety of the triple therapy has been previously demonstrated and the most common side effects were nasopharyngitis (a cold), headache and back pain.
Where is the study run from?
Robarts Research Institute, Western University (Canada)
When is the study starting and how long is it expected to run for?
August 2022 to August 2023
Who is funding the study?
GlaxoSmithKline
Who is the main contact?
Grace Parraga, PhD, gparraga@uwo.ca
Contact information
Public, Scientific, Principal Investigator
Robarts Research Institute
Room 5135
1151 Richmond Street North
London
N6A 5B7
Canada
| Phone | +1 (0)519 931 5265 |
|---|---|
| lungimaging@uwo.ca |
Study information
| Study design | Single-center open-label single-arm pilot study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Laboratory, University/medical school/dental school |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | Evaluation of triple therapy using magnetic resonance imaging in asthma (ETHA) |
| Study acronym | ETHA |
| Study hypothesis | The objective was to quantify small-airways dysfunction using 129Xe MRI ventilation-defect-percent (VDP) before and after 6-weeks ICS/LABA with long-acting muscarinic antagonist (LAMA) and evaluate potential responses with respect to type 2 inflammation. |
| Ethics approval(s) |
Approved 06/07/2022, Western University Health Science Research Ethics Board (Office of Human Research Ethics Room 5150, Support Services Building, Western University, 1151 Richmond Street North, London, N8G 1G9, Canada; +1 (0)519 661 3036; ethics@uwo.ca), ref: 118122 |
| Condition | Step 4 or 5 asthma according to Global Initiative for Asthma (GINA) |
| Intervention | Participants stop previous ICS/LABA medication on the day prior to the first of three visits, before treatment initiation (week 0; Visit 1, V1). At V1, blood is drawn for complete blood count and chest CT, FeNO, ACQ-6, Asthma Quality-of-Life Questionnaire (AQLQ) and St George’s Respiratory Questionnaire (SGRQ) are completed. Spirometry, plethysmography, airwave-oscillometry and 129Xe MRI are performed before (pre-bronchodilator; pre-BD) and 15 minutes after (post-bronchodilator; post-BD) inhalation of 4 × 100μg Novo-Salbutamol Hydrofluoroalkane (Teva Novopharm Ltd., Toronto, ON, Canada) using an AeroChamber (Trudell Medical International, London, ON, Canada). After being trained on the use of a proprietary multi-dose dry powder inhaler (ELLIPTA), participants will inhale the first dose of FF/UMEC/VI (200/62.5/25 µg) at the study centre, under observation, with instructions to continue once every morning until Visit 2 (V2, 6 weeks ± 5 days after V1) or Visit 3 (V3, 12 weeks ± 5 days after V2). All measurements acquired at V1 are repeated on V2 and V3, except for blood work and CT. Study doses are provided on V1 and again on V2 for those participants who decided to continue to V3. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Dose response |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Fluticasone-furoate/umeclidinium/vilanterol 200/62.5/25 μg (FF/UMEC/VI) (Trelegy) |
| Primary outcome measure | Ventilation defect percent (VDP) measured using 129Xe MRI at V2 |
| Secondary outcome measures | 1. Change in FeNO levels measured using the FeNO device between baseline and visit 2 2. Change in forced expiration volume in one second measured using spirometry between baseline and visit 2 3. Change in forced vital capacity measured using spirometry between baseline and visit 2 4. Change in residual volume measured using plethysmography between baseline and visit 2 5. Change in total lung capacity measured using plethysmography between baseline and visit 2 6. Change in oscillometry measurements of small-airway resistance (R5-19) measured using the forced oscillation technique between baseline and visit 2 7. Change in lung clearance index (LCI) measured using multiple breath nitrogen washout between baseline and visit 2 8. Change in asthma control measured using the ACQ-6 questionnaire between baseline and visit 2 |
| Overall study start date | 08/08/2022 |
| Overall study end date | 25/08/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 75 Years |
| Sex | Both |
| Target number of participants | 32 |
| Total final enrolment | 31 |
| Participant inclusion criteria | 1. Participant understands study procedures and is willing to participate in the study as indicated by the participant's signature 2. Provision of written, informed consent prior to any study-specific procedures 3. Males and females with a clinical diagnosis of eosinophilic asthma (based on FENO ≥40ppb, blood eosinophilia ≥200 cells/μl at screening) aged 18 to 70 years, inclusively, at the time of Visit 1 (enrolment), under the care of a respirologist 4. FEV1 ≥35 and ≤80% predicted 5. Participant is a current non-smoker and non-vaper, having not smoked tobacco or cannabis, pipe or cigar or vaped any product for at least 12 months prior to the study with a tobacco smoking history of no more than 1 pack-year (i.e. 1 pack per day for 1 year). 6. Women of childbearing potential (after menarche) must use a highly effective form of birth control (confirmed by the investigator or designee) A highly effective form of birth control includes true sexual abstinence, a vasectomized sexual partner, Implanon®, female sterilization by tubal occlusion, any effective intrauterine device (IUD)/levonorgestrel intrauterine system (IUS), Depo-ProveraTM injections, oral contraceptive and Erva PatchTM or NuvaringTM 7. Women of childbearing potential (after menarche) must agree to use a highly effective form of birth control, as defined above, from enrolment, throughout the study duration, and 8 weeks after the last dose of the study drug, with negative pregnancy test result at Visit 1 8. Male participants who are sexually active must agree to use a double barrier method of contraception (condom with spermicide) from the first dose of the study drug until 8 weeks after the last dose 9. Participant has documented treatment with a stable dose of low to medium dose inhaled corticosteroids (defined as >250 and ≤500 mcg fluticasone proprionate/day or equivalent or, >400 to ≤800 mcg Budesonide/day for at least 6 months prior to enrolment long-acting β2-agonist (LABA) for at least 6 months prior to enrolment 10. Participant has blood eosinophils ≥ 200 cells/μl or FENO ≥25ppb at Visit 1 for all participants except for those with previous biologic therapy without washout who will be required to washout prior to screening. 11. Participant has ACQ-6 ≥ 1.5 at visit 1 12. Participant has a history of poorly controlled asthma (i.e. ≥2 exacerbations in the past 24 months) |
| Participant exclusion criteria | 1. Participant is, in the opinion of the investigator, mentally or legally incapacitated, preventing informed consent from being obtained, or cannot read or understand written material 2. Participant has clinically important pulmonary disease other than asthma (e.g. active lung infection, chronic obstructive pulmonary disease, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha-1 antitrypsin deficiency and primary ciliary dyskinesia) or been diagnosed with pulmonary or systemic disease other than asthma that is associated with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome), except for those atopic conditions that can be associated with asthma (e.g. allergic rhinitis, sinusitis with or without polyposis, eczema, and eosinophilic esophagitis) 3. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Qualified Investigator and/or could affect the safety of the participant throughout the study, influence the findings of the study or their interpretations, or impede the participant's ability to complete the entire duration of the study, as assessed by the Qualified Investigator. 4. Known history of allergy or reaction to the study drug formulation 5. Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date of informed consent 6. Clinically significant asthma exacerbation, defined as a change from baseline deemed clinically relevant in the opinion of the Qualified investigator, including those requiring the use of OCS, or an increase in maintenance dosage of OCS within 30 days prior to the date of informed consent. Participants with an exacerbation after providing informed consent but prior to treatment start will be excluded from the study 7. Receipt of immunoglobulin or blood products within 30 days prior to the date of informed consent 8. Receipt of live attenuated vaccines 30 days prior to the date of enrolment 9. Previously randomized in any FF/UMEC/VI 200/62.5/25ug study 10. Planned surgical procedure during the conduct of the study 11. Concurrent enrolment in another clinical trial 12. Participant has history of alcohol or drug abuse within 12 months prior to the date of informed consent 13. Participant is a female who is ≤8 weeks post-partum or breast feeding an infant 14. Participant is pregnant, or intends to become pregnant during the time course of the study 15. Participant is unable to perform MRI breath-hold maneuver 16. Participant is unable to perform spirometry maneuver 17. Participant is hospitalized or has had a major surgical procedure, major trauma requiring medical attention, or significant illness requiring medical attention within 4 weeks of Visit 1 18. 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 19. In the opinion of the investigator, participant suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI, such as severe claustrophobia 20. Participant has 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. |
| Recruitment start date | 08/08/2022 |
| Recruitment end date | 19/07/2023 |
Locations
Countries of recruitment
- Canada
Study participating centre
1151 Richmond Street North
London
N6A 5B7
Canada
Sponsor information
University/education
1151 Richmond Street North
London
N6A 5B7
Canada
| Phone | +1 (0)519 931 5265 |
|---|---|
| gparraga@uwo.ca |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- GlaxoSmithKline plc., GSK plc., GSK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/08/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated and/or analyzed during the current study will be available upon request from Dr Grace Parraga (gparraga@uwo.ca). Data is anonymized; written informed consent was provided by all participants; data will be available starting today for 5 years; all research data are available except for age and sex. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 11 | 08/07/2022 | 15/03/2024 | No | No |
| Basic results | 18/03/2024 | No | No |
Additional files
Editorial Notes
18/03/2024: The basic results have been uploaded as an additional file.
15/03/2024: Study's existence confirmed by the Western University Health Science Research Ethics Board.
