Alpha 1-Antitrypsin Deficiency, Chronic Obstructive Pulmonary Disease
Conditions
Keywords
MRI, COPD, A1ATD
Brief summary
This study aims to use novel proton-based MRI techniques to assess lung function and structure in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD) and alpha-1-anti-trypsin deficiency (A1ATD). These novel MRI measures will be compared to matched contemporary clinical diagnostic tools, namely pulmonary function tests (PFTs) and computed tomography (CT) scans. MRI has the advantages of avoiding ionising radiation exposure (unlike CT scans) and can also provide regional measures of lung function (unlike PFTs which provide global measures of function). In addition, these MRI techniques do not require the use of any inhaled or injected contrast agents. Some patients enrolled in this study will be undergoing a lung volume reduction (LVR) procedure as part of their normal clinical care. LVR is an intervention for patients with severe lung disease and hyperinflation. It is a palliative therapy that helps to reduce lung hyperinflation through insertion of small valves in the airway or surgical removal of parts of the lung. This can lead to improvements in symptoms such as breathlessness and improve exercise tolerance due to better functioning of the lung. In this study, we will explore how lung MRI measures can be used to assess patients before and after an LVR intervention. This study will take place at the University of Nottingham in collaboration with Nottingham University Hospitals NHS Trust. The study will last for 3 years and participants will be asked to attend a screening visit (lasting up to 1 hour) and either one or two study visits (each lasting up to 3 hours).
Detailed description
This is a single centre pilot study. The research team aims to recruit adult healthy volunteers and adult patient volunteers with COPD and A1ATD. We have used similar proton-based MRI techniques in healthy volunteers and people with other lung diseases and the MRI scans have been well tolerated. All participants will be adults (both male and female) who can give informed consent and are able to undertake the study procedures. Potential participants who cannot have an MRI scan for safety reasons (e.g. have a pacemaker) will not be recruited. During study visits, all research activities will be observed by a member of the research team. During the screening visit (following consent), the following information and measures will be taken: Relevant past medical history, COPD assessment tool (questionnaire), height, weight, blood pressure and pulse oximetry. During study visits, a combination of structural and functional lung MRI scans will be performed with the participant lying in the scanner. Participants will be asked to breathe normally during scans and may also be asked to perform breathing manoeuvres such as holding their breath temporarily. The participants will be assigned unique codes, and their data will be anonymised. Participants' medical reports will only be accessed for study purposes and will be treated as confidential. The investigators will aim to use the data to plan future studies, and the data from this study may contribute to publications and presentations. Participants will not be identified in any publications arising from the research. The data obtained will be published without any identifying information.
Interventions
DIAGNOSTIC_TESTLung MRI scan
Participants will have a combination of structural and functional lung MRI scans. These scans will involve lying in a conventional MRI scanner while free breathing and may include additional breathing manoeuvres such as temporarily holding breath.
Sponsors
Nottingham University Hospitals NHS Trust
University of Nottingham
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Workstream 1 Inclusion criteria (Adult Healthy Volunteers) * Male or female aged 18 years and over * Capacity to give informed consent * Normal blood pressure (systolic BP \> 90 mmHg and diastolic BP \>50 mmHg) * Resting heart rate \> 50bpm * For women, negative urinary β-hCG at the screening and subsequent visits (where clinical uncertainty of pregnancy) * Subject able to hold breath for 10 seconds * Subject able to understand the requirements of the study and to cooperate with the study procedures * Subject has normal lung function by spirometry criteria * Smoking history of \> 10 pack years of tobacco smoking Workstream 1
Exclusion criteria
(Adult Healthy Volunteers) * Unsuitable for MRI scanning (e.g. have metal implants or pacemaker or contraindicated following questionnaire) * Subject deemed unlikely to comply with instructions during imaging * Subject not deemed fit enough to tolerate procedure * Subject deemed unsuitable by clinical investigator for other reasons * Abnormal spirometry Workstream 2 Inclusion criteria (Adults with chronic obstructive pulmonary disease) * Male or female aged 18 years and over * Capacity to give informed consent * Normal blood pressure (systolic BP \> 90 mmHg and diastolic BP \>50 mmHg) * Resting heart rate \> 50bpm * For women, negative urinary β-hCG at the screening and subsequent visits (where clinical uncertainty of pregnancy) * Subject able to hold breath for 10 seconds * Subject able to understand the requirements of the study and to cooperate with the study procedures * Diagnosis of COPD made by respiratory physician and confirmed by spirometry criteria (FEV1/FVC ratio \< 0.7) and \> 10 pack years of tobacco smoking. Workstream 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To acquire structural and functional proton-based lung MRI scans from patients with COPD and COPD due to A1ATD and produce baseline data for these groups to inform future clinical studies | 3 years | To compare functional MRI outcomes with matched clinical physiological data (e.g. pulmonary function tests) To compare structural lung images with matched conventional imaging techniques done for clinical reasons (e.g. computed tomography) of the diaphragm and lungs |
Secondary
| Measure | Time frame |
|---|---|
| To assess the ability of participants of each group to adhere to the protocols, thus informing the study design of future trials | 3 years |
| To assess any change of MR outcomes across study visits for those participants undertaking more than one MR scanning visit. | 3 years |
| To assess any change of MR outcomes across study visits for participants who undergo LVR | 3 years |
Countries
United Kingdom
Contacts
Primary ContactJonathan Philip Brooke
Backup ContactZachary Peggs
Outcome results
None listed