Plain English Summary
Background and study aims
The aorta is the main blood vessel that comes out of the heart and rapidly distributes blood to the whole body. In some people, the aorta becomes swollen (an aneurysm) especially as it passes through the abdomen. These 'abdominal aortic aneurysms' (AAA) usually grow slowly without causing any symptoms, but they can sometimes burst or need to be fixed by an operation.
Currently aneurysms are monitored by ultrasound scanning. In this research study, we want to see if magnetic resonance imaging (MRI) might be a better way of following patients who have an aneurysm. To do this, we will use a contrast agent (Ferumoxytol) that contains tiny iron filings that are eaten up by cells (called macrophages) in the wall of the aneurysm. We can then use the MRI scanner to get a picture of your aneurysm. In a small
group of patients, we have recently shown that we can use this MRI scan to detect 'hotspots' in the wall of some aneurysms that seemed to grow more quickly than others. The aim of the current study is to confirm these findings in a larger group of patients and also to see whether MRI scanning can identify patients with aneurysms at risk of bursting or those that go on to need an operation.
Who can participate?
Patients with an AAA who are more than 40 years old can take part in the study. Women of child-bearing potential should not take part in this study.
What does the study involve?
At the start of the study, you will come to the hospital on two separate days. On the first day we will ask you about any existing or previous medical conditions that you might have, take a blood sample (about 4 teaspoonfuls 20 mLs) and check your blood pressure. You will have an MRI scan of your abdomen to look at your aneurysm. Through a drip in your arm (in a blood vessel) you will receive a drug called Buscopan which helps stop the
digestive movements in your abdomen so we can get a clear picture using the MRI scanner. If you are unable to have this drug it will not be given but the scan will go ahead. You will also have a CT scan of your abdomen at this appointment. Computed Tomography (CT) scanning uses an x-ray machine to give a detailed 3D picture. In order for the scanner to give a clear picture, you will be given an injection of a standard contrast agent into the drip in your arm. CT scanning is often used to assess your aneurysm, for example if an operation is being considered. As part of this study, you will have a CT scan when you enter the study and two years after entry into the study. This will give us detailed information about whether your aneurysm has changed in size. After both the scans, you will receive Ferumoxytol through the drip in your arm and we will monitor your blood pressure for 30
minutes after this. This visit will last about three hours.
The following day you will return to the hospital to have a further MRI scan of your abdomen to look at your aneurysm. You will need to have a drip in your arm again, as you need to have buscopan before the scan (as you did on the first day). The second visit will take about 40 minutes.
Either on day 1 or day 2 we will measure the stiffness of your arteries by recording your blood pressure from your arm and leg. This is called pulse wave analysis. For this part of the study we ask you not to eat anything and avoid caffeine (water is fine) for 4 hours before your appointment time. In addition you should avoid alcohol for 24 hours before this appointment. We will inform you before you first appointment which day this will be performed on.
A small number of patients (40) will be asked to return for a further 2 visits, one month and one year after the original visit to redo the scans with repeated doses of ferumoxytol and buscopan. You would get 2 extra MRI scans at 1 month plus ferumoxytol and buscopan and 2 extra MRI scans at 1 year plus ferumoxytol and buscopan. This will determine how repeatable the scan is. If you agree to take part in this research study, we will ask you if you
want to take part in these additional study visits at the time of consent. As you have an AAA, you will be routinely attending the hospital every 6 months for an ultrasound scan of your aneurysm so it can be monitored. This will still happen when you take part in this research study. A blood sample (about 4 tea spoons 20 mLs, which would not normally be done) will be taken. In addition pulse wave analysis will also be repeated at these 6 monthly visits. This will add about 40 minutes onto your visit. If you require surgery to treat your aneurysm during your involvement in the study, we would like to take a sample of tissue from the wall of the aneurysm after it has been repaired. This tissue would normally be discarded. The sample would be tested to assess the strength of the wall and its structure. You will be part of the study for 2 years.
What are the possible benefits and risks of participating?
By taking part in this research study it is hoped that the findings of this study will benefit other patients with aneurysms in the future. It is unlikely that you will encounter any side-effects from taking part in this study. MRI scanners do not use X-rays but instead use strong magnets which do not cause any problems for the vast majority of people, but for a small number (such as those who have a pacemaker for their heart) it is advisable to avoid having one of these scans.
A CT scan is a routine medical procedure and it is possible that you would require CT scans to assess your AAA even if you were not part of this trial. The scan itself is associated with very few side effects. The most important potential side effect, as with any x-ray scan, is the use of radiation. The amount of radiation used during the scan varies but is around 2 to 3 times the amount that you would normally receive in a year from background natural
sources of radiation, such as from rocks in the Earths crust. The lifetime risk of developing cancer from the x-rays involved in the CT scan is very small.
Before giving you the CT contrast agent, we will check the function of your kidneys and ask if you have any known allergies to this contrast agent. If there are any concerns regarding either of these two factors, you will not be given the contrast agent. Ferumoxytol is routinely used to treat people who have low levels of iron in their blood. The iron filings are absorbed into the bodys general iron stores. Whilst most people do not have any symptoms when receiving the contrast agent, a small minority of people experience mild side-effects. These are uncommon (affecting between 1 to 3 in every 100 patients) and include; nausea, vomiting, abdominal or chest pain, dizziness, low blood pressure, headache, shortness of breath, cough, skin rash or itch, swelling of the ankles and muscle cramps. As with any medication, serious side effects such as severe allergies are possible but are extremely rare. We will monitor your blood pressure 30 minutes after you are given the Ferumoxytol.
Most people do not have any symptoms when receiving buscopan, however a minority of people experience mild side effects. These are very uncommon (affecting 1 in 1000) and include; dry mouth, a fast heart rate, a skin rash or itch, constipation. As with any medication, serious side effects, such as severe allergies can happen but are rare. There is a possibility that the scans performed in this study could reveal an incidental health problem that you or your doctor is unaware of. If this were to happen we would discuss this with you and your doctor, and arrange appropriate further tests and treatments as
necessary. This may be viewed as a positive thing but it must be remembered that this could affect your insurance policies. You should also understand that there may be other conditions that do not show up on this kind of scan.
Where is the study run from?
The study is being run by the University of Edinburgh and will be taking place in Edinburgh, Glasgow and Forth Valley.
When is the study starting and how long is it expected to run for?
The study will run for 4 years between September 2012 and September 2016. Recruitment will take 1.5 years and each patient will be followed up for 2 years.
Who is funding the study?
The study is being funded by a grant from the Medical Research Council.
Who is the main contact?
Prof. David Newby
Prof David Newby
University of Edinburgh
Centre for Cardiovascular Science
51 Little France Crescent
+44 (0)131 242 6515
Magnetic Resonance Imaging using ultrasmall supermagnetic particles of iron oxide in patients under surveillance for abdominal aortic aneurysms to predict rupture or surgical repair
Ruptured Abdominal Aortic Aneurysms (AAA) is the thirteenth commonest cause of death in the United Kingdom and accounts for 6,800 deaths each year in England and Wales. Population screening halves the mortality associated with AAA, and has led to the establishment of national screening and surveillance programmes. However, AAA surveillance is complex because of the non-linearity and unpredictability of expansion rates. Although the best predictor of aneurysm expansion is the aneurysm diameter, up to one fifth of ruptured AAA are less than 55 mm in diameter, and many patients present with diameters considerably greater than 55 mm without prior symptoms or rupture. There is therefore a major unmet clinical need to predict aneurysm growth and rupture more accurately so that surgeons can better target preventative potentially life-saving surgery. We have developed a novel magnetic resonance imaging method that is based upon the known biological processes underlying aneurysm expansion and rupture. For the first time, this study proposes to assess this novel approach to identify aneurysms that are likely to expand more rapidly and potentially rupture. This technique would provide potentially important additional information to the current simplistic gold-standard of ultrasound measurement of aneurysm diameter.
The Primary Objective of the study is to determine whether mural uptake of ultrasmall supermagnetic particles of iron oxide (USPIO) provides incremental risk prediction in addition to standard risk markers such as aneurysm diameter, smoking and blood pressure.
The secondary objectives is for patients under surveillance for abdominal aortic aneurysms, to determine whether mural uptake of USPIO:
1. Correlates with the rate of aneurysm expansion
2. Occurs more commonly in patients who progress to surgery or whose aneurysm subsequently ruptures
3. Co-localises with, or relates to, areas of biomechanical stress
4. Occurs in a reproducible manner
We will investigate other inter-related mechanisms associated with aneurysm growth. We will specifically explore the added value of biomechanical stress modeling as we suspect co-localisation of both USPIO uptake and areas of high mechanical stress could act synergistically and cause more marked aneurysm growth. We will also examine correlates with other blood biomarkers including regulators of extracellular matrix turnover (such as matrix metalloproteinases and tissue inhibitors of metalloproteinases) and vascular inflammation (such as C-reactive protein and interleukin-6).
East of Scotland Ethics Research Service REC 1 (EoSRES REC 1), 28/08/2012, REC ref: 12/ES/0068
Prospective observational cohort study
Primary study design
Secondary study design
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Abdominal Aortic Aneurysm
All patients will have a full formal and standardized clinical assessment at the first study visit that will include history, examination, documentation of cardiovascular risk factor profile (smoking status, family history, hypertension, hyperlipidaemia, diabetes mellitus) and concomitant medications (antihypertensive medication, etc). This assessment will be updated at each clinic attendance (standard clinical care is 6 monthly appointments).
Blood pressure, pulse wave analysis and velocity will be performed at the first and last study visit. In Edinburgh, patients will undergo these investigations at each 6 monthly appointment.
Pulse wave velocity involves the blood flow in the artery in the neck and the artery in the groin being checked using a noninvasive probe and the distance between the 2 sites recorded. Pulse wave analysis involves the blood flow in the artery in the arm being assessed, again with a noninvasive probe.
Blood samples (20 mL on each visit) will be collected at the first and last study visits. Patients recruited from Edinburgh will have blood samples collected every 6 months for analysis of markers of inflammation in the blood.
Ultrasound of the abdominal aorta
Patients will undergo 6month ultrasound imaging as part of standard care for the surveillance programme to measure the maximal anteroposterior diameter of the aneurysm.
Computed tomography (CT) of the abdominal aorta:
CT scans will occur at the first study visit and at 24 months. In cases where study participants undergo emergency repair of a ruptured abdominal aortic aneurysm then a CT scan may not be performed.
Magnetic resonance imaging (MRI) of the abdominal aorta
Magnetic resonance imaging will be conducted and Ferumoxytol administered at the first study visit. 24-36 hours after administration of Ferumoxytol a repeat MRI scan will be performed. The MRI scanning protocol will be completed prior to the procedure.
Analysis of tissue from the abdominal aortic wall
Patients recruited in Edinburgh who undergo elective repair of their abdominal aortic aneurysm will have tissue sampled from the discarded part of the aneurysm. This tissue will be stored and analysed for mechanical testing and then discarded in accordance with the human tissue act.
Duration of appointments
The first study visit is expected to take 34 hours. 6 monthly appointments for ultrasound scans are part of routine clinical care. The final CT scan at 2 years will take 30 minutes.
Patients will be recruited over an 18month period and followed up for 24 months.
Primary outcome measures
The composite of aneurysm rupture or aortic aneurysm repair
Secondary outcome measures
1. The rate of aneurysm rupture
2. The rate of surgical repair of the aneurysm
3. Aneurysm growth rate
4. All-cause and aneurysm-related mortality
5. We will conduct exploratory analyses examining the interactions between mural USPIO uptake, biomechanical stress, clinical risk factors and serum biomarkers of extracellular matrix turnover and inflammation.
Clinicians involved directly with patient surveillance and care will be blinded to the magnetic resonance imaging findings of mural USPIO uptake.
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Abdominal aortic aneurysms measuring ≥40 mm in anteroposterior diameter on ultrasound scanning
2. Age ≥40 years. Patients with abdominal aortic aneurysms less than 40 years may have a connective tissue disorder and a different aetiology to their disease
Target number of participants
Participant exclusion criteria
1. Patients expected to, or already received, imminent elective or emergency surgical or endovascular repair
2. Contraindication to magnetic resonance imaging scanning identified from magnetic resonance imaging safety questionnaire
3. Patients refusing or unable to give informed consent
4. Woman with child-bearing potential and who are breastfeeding will not be enrolled into the trial (woman who have experienced menarche, are pre-menopausal, have not been sterilised or who are currently pregnant)
5. Intercurrent illness including patients with a systemic inflammatory disorder or underlying malignancy (life expectancy < 2 years)
6. Renal dysfunction (eGFR ≤30 mL/min/1.73m2)
8. Contraindication to ferumoxytol (evidence of known iron overload, hemochromatosis, known hypersensitivity to ferumoxytol or its components or anaemia not caused by iron deficiency)
9. Contraindication to Iodine
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
University of Edinburgh
University of Edinburgh / NHS Lothian (UK)
Academic and Clinical Central Office for Research and Development (ACCORD)
Research & Development Management Suite
The Queen's Medical Research Institute
47 Little France Crescent
+44 (0)131 242 9262
Efficacy and Mechanism Evaluation Programme (MRC UK) ref: 11/20/03
NIHR Efficacy and Mechanism Evaluation programme, EME
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting