Clinical trial NCT04966221: Functional and Structural Lung Imaging in Chronic Obstructive Pulmonary Disease
Official title: Functional and Structural Lung Imaging in Chronic Obstructive Pulmonary Disease
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Obstructive Pulmonary Disease
Alpha 1-Antitrypsin Deficiency
Keywords: MRI
COPD
A1ATD
Lead sponsor: University of Nottingham
Sponsor class: OTHER
Collaborators: name: Nottingham University Hospitals NHS Trust
First posted: 2021-07-19
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will include up to 25 participants in each of the three workstreams:

Workstream 1 - Adult healthy volunteers Workstream 2 - Adults with chronic obstructive pulmonary disease Workstream 3 - Adults with COPD due to alpha-1-antitrypsin deficiency - 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.

Eligibility 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 Exclusion criteria (Adults with chronic obstructive pulmonary disease)

* Unsuitable for MRI scanning (e.g. have metal implants or pacemaker or contraindicated following questionnaire)
* Acute illness considered to be of sufficient severity to prevent safe MRI scanning. In this instance, the subject will be invited to be rescreened \> 4 weeks later.
* 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

Workstream 3 Inclusion criteria (Adults with COPD due to alpha-1-antitrypsin deficiency - A1ATD)

* 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 A1ATD (PiZZ or PiZ-) and either evidence of emphysema on a previous clinical CT scan or evidence of airways obstruction

Workstream 3 Exclusion criteria (Adults with COPD due to alpha-1-antitrypsin deficiency - A1ATD)

* Unsuitable for MRI scanning (e.g. have metal implants or pacemaker or contraindicated following questionnaire)
* Acute illness considered to be of sufficient severity to prevent safe MRI scanning. In this case, the subject will be rescreened \>4 weeks later
* 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

Primary outcomes:
measure: 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
timeFrame: 3 years
Secondary outcomes:
measure: To assess the ability of participants of each group to adhere to the protocols, thus informing the study design of future trials
timeFrame: 3 years
measure: To assess any change of MR outcomes across study visits for those participants undertaking more than one MR scanning visit.
timeFrame: 3 years
measure: To assess any change of MR outcomes across study visits for participants who undergo LVR
timeFrame: 3 years
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Sir Peter Mansfield Imaging Centre, University of Nottingham
state: Nottinghamshire
Study officials:
affiliation: The University of Nottingham
name: Jonathan Philip Brooke
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Nottingham
name: Zachary Peggs
role: PRINCIPAL_INVESTIGATOR
References: