AtherosclerosisMICANCT01674257
Metabolic Imaging in Carotid Atherosclerosis
An observational study of Atherosclerosis and Stroke, run by University of Edinburgh at 1 site in United Kingdom.
Trial summary
Hardening of the arteries (atherosclerosis) is a common disorder that causes heart attacks and strokes. PET CT and contrast-enhanced MRI scans are two new ways of assessing atherosclerosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atherosclerosis, Stroke
- What is being tested?
- USPIO (ferumoxytol)-enhanced MRI scan, 18f-Fluoride PET/CT scan and 18F-Flurodeoxyglucose PET/CT scan
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 26 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 Oct 2012to 31 Jul 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients referred for carotid endarterectomy for symptomatic carotid artery stenosis.
Who may be able to join
- Patients with carotid stenosis due to undergo carotid endarterectomy.
Who cannot join
- Patients with new stroke and a modified Rankin score >3
- Chronic Kidney Disease with eGFR of <30 mL/min/1.73m2
- Pregnant women
- Poorly controlled diabetes mellitus (HbA1c > 8.5%) or diabetes mellitus requiring insulin
- Prior ipsilateral carotid intervention
- Prior neck irradiation
Show all 14Show fewer
- Inability to tolerate the supine position
- Participation in the study would result in delay to surgery
- Psychiatric illness/social situations that would limit compliance with study requirements
- Specific contraindications to MRI (e.g. pacemaker)
- History of allergic reaction attributed to ferumoxytol or similar
- Known or suspected iron overload (genetic haemochromatosis or history of multiple transfusions)
- History of allergic reaction attributed to 18F-FDG or 18F-NaF or similar
- History of allergic reaction to iodine or iodine-based contrast media
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Clinical Research Imaging Centre
Edinburgh, EH16 4TJ
About this study
Official title: An Investigation of the Role of 18F-Sodium Fluoride and 18F-Flurodeoxyglucose PET CT and USPIO Enhanced MRI in Imaging Carotid Artery Inflammation and Mineralization.
Hardening of the arteries (atherosclerosis) is a common disorder that causes heart attacks and strokes. PET CT and contrast-enhanced MRI scans are two new ways of assessing atherosclerosis. The investigators propose to perform PET CT and MRI scans on patients with hardening of the neck arteries due to undergo surgery to remove the hardened areas. The investigators will then be able to compare the hot spots found on these scans with what the investigators can see in the removed specimens under the microscope in the laboratory. This will give investigators insight into the value of PET CT and MRI as tools for assessing atherosclerosis. It will also provide the investigators with new information relating to the underlying processes that give rise to atherosclerosis and will pave the way for the future development of new treatments.
Read the detailed description
Hardening of the arteries (atherosclerosis) is a very common health problem that can lead to fatal or disabling heart attacks and strokes. On many levels, it remains an incompletely understood illness.
Until relatively recently, the only way of assessing the severity of, or risk posed by, atherosclerosis was to measure the degree to which it narrowed a particular blood vessel. This method only tells part of the story; he investigators now know that frequently the 'culprit area' of atherosclerosis that causes the heart attack or stroke does not necessarily result in narrowing of the blood vessel - i.e. if the investigators only measure narrowness the investigators will miss lots of 'bad' atherosclerosis. As such, there is a pressing need to identify more sophisticated techniques of assessing the disease in order that people who are at higher risk of heart attack or stroke can be identified early and offered appropriate preventative treatment.
Techniques that provide this extra information could also significantly shorten the time it takes to get new treatments and drugs to market by providing a faster and more cost-effective way of assessing these treatments early in their development. Furthermore, in exploring new techniques that reflect more accurately what is going on within atherosclerosis in the body, deeper insight into the condition will be gained. This will in turn lead to the development of new treatments.
PET/CT scans and USPIO (a kind of tracer) enhanced MRI scans are two such techniques that demonstrate particular promise. These scanning methods not only provide more information about the composition and architecture of the atherosclerosis but can provide data about the processes (at the chemical and cellular level) that underlie the disease.
Inflammation and calcification (deposits of calcium) are two biological processes that are known to be very important in the genesis of atherosclerosis. PET/CT and USPIO enhanced MRI can detect these processes.
Most strokes and mini-strokes are caused by a narrowing in the neck artery. If a patient with mini-stroke or stroke has a narrowing (atherosclerosis) in their carotid artery they are normally offered an operation to remove the atherosclerosis (endarterectomy), the piece of atherosclerosis is then normally discarded. This scenario affords a perfect opportunity to explore new scanning techniques.
The investigators propose to explore the feasibility and value of using PET/CT (using 18F-FDG and 18F-NaF - two tracers known to highlight inflammation and calcification) and USPIO enhanced MRI to assess atherosclerosis. The investigators will do this by scanning patients who have just had a mini-stroke or minor stroke and are due to undergo endarterectomy. The investigators will then be able to define what is going on at the level of the genes and the cells that causes 'hot spots' on CT/PET and MRI.
- Conditions
- Atherosclerosis, Stroke
- Being tested
- USPIO (ferumoxytol)-enhanced MRI scan, 18f-Fluoride PET/CT scan, 18F-Flurodeoxyglucose PET/CT scan
- Keywords
- Atherosclerosis, Stroke, Positron-emission tomography, Ferumoxytol, Magnetic resonance imaging, Genetics, Calcification, Inflammation, Flurodeoxyglucose F18, Radiopharmaceuticals
- Medical subject headings
- Atherosclerosis, Stroke, Calcinosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
USPIO (ferumoxytol)-enhanced MRI scanOther
Two separate MRI scans will form this intervention. A baseline scan followed by an infusion of USPIO (ferumoxytol), followed by another MRI scan.
18f-Fluoride PET/CT scanRadiation
18F-Flurodeoxyglucose PET/CT scanRadiation
| Study group | Role | What they receive |
|---|---|---|
| Carotid Endarterectomy | Patients due to undergo carotid endarterectomy for symptomatic carotid artery stenosis will undergo an 18F-Fluoride PET/CT, an 18F-Flurodeoxyglucose PET/CT and a USPIO (ferumoxytol)-enhanced MRI scan (2 MRI scans). Receives: Other: USPIO (ferumoxytol)-enhanced MRI scan; Radiation: 18f-Fluoride PET/CT scan; Radiation: 18F-Flurodeoxyglucose PET/CT scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Standardized Uptake Value (SUV) for 18F-Fluoride of the ipsilateral carotid artery
The mean and maximum SUV (using 18F-NaF) of the ipsilateral carotid artery will be calculated and compared to its contra lateral partner. The SUV is a validated quantitative assessment of PET radiotracer uptake.
Measured: 1-2 days after PET/CT scan
Secondary outcomes (8)
The SUV of 18F-Flurodeoxyglucose on PET/CT of the ipsilateral carotid artery
The mean and maximum SUV (using 18F-Flurodeoxyglucose) of the ipsilateral carotid artery will be calculated and compared to its contra lateral partner.
Measured: 1-2 days after PET/CT scan
A correlation between the ipsilateral carotid SUV of 18F-Flurodeoxyglucose and tissue markers of inflammation and apoptosis.
Sections of excised atheroma that demonstrate uptake of 18F-Flurodeoxyglucose will be subjected to histological examination. A variety of immunohistochemical markers of inflammation and apoptosis will be quantitatively assessed for correlation with the degree of radioligand uptake. Tissue showing no radioligand uptake will be used as control.
Measured: Approximately 1 month after PET/CT scan
A correlation between ipsilateral carotid SUV of 18F-Fluoride and the gene expression characteristics of excised plaque.
Sections of excised atheroma that demonstrate uptake of 18F-Fluoride will be subjected to gene expression profiling. Sections of plaque that do not show uptake will be used as controls. The resulting data will be analyzed to explore the variation in gene expression between subjects and between areas of differing radioligand uptake. Genes of particular interest (either identified during expression profiling or selected beforehand) will be further studied using quantitative PCR.
Measured: Approximately 1 month after the PET/CT scan
A correlation between the ipsilateral carotid SUV of 18F-Fluoride and tissue markers of apoptosis and calcification.
Sections of excised atheroma that demonstrate uptake of 18F-Fluoride will be subjected to histological examination. A variety of immunohistochemical markers of calcification and apoptosis will be quantitatively assessed for correlation with the degree of radioligand uptake. Tissue showing no radioligand uptake will be used as control.
Measured: Approximately 1 month after the PET/CT scan
The presence or absence of USPIO (ultra-small superparamagnetic particles of iron oxide) uptake on MRI (magnetic resonance image) within the ipsilateral carotid artery compared to its contralateral partner.
USPIOs are known to accumulate within activated macrophages in inflamed atheroma. This causes a demonstrable drop in T2* signal on MR.
Measured: 1-2 days after MRI scan
A correlation between the ipsilateral carotid USPIO uptake and tissue markers of inflammation and apoptosis.
Sections of excised atheroma will be co-stained for USPIO and a variety of immunohistochemical markers of inflammation and apoptosis.
Measured: 1 month after MRI scan
A correlation between the ipsilateral carotid USPIO uptake and gene expression characteristics of excised atheroma.
Sections of excised atheroma that demonstrate uptake of USPIO will be subjected to gene expression profiling. Sections of plaque that do not show uptake will be used as controls. The resulting data will be analyzed to explore the variation in gene expression between subjects and between areas of differing USPIO uptake. Genes of particular interest (either identified during expression profiling or selected beforehand) will be further studied using quantitative PCR.
Measured: 1 month after the MRI scan
The ipsilateral carotid radioactivity, arterial blood radioactivity and whole blood fluoride concentration measured over time
The kinetics of 18F-Fluoride in atherosclerosis have not yet been defined. Using data from the PET scanner in list mode and regular arterial and venous blood sampling in 20 patients (a subset of the total) we will define a model describing the radiopharmacokinetics of 18F-Fluoride in carotid atheroma.
Measured: During the 18F PET/CT scan
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2012 (estimated)
- Study start10 Oct 2012
- Primary completion30 Jun 2014
- Study completion31 Jul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian, British Heart Foundation
- Responsible party
- Sponsor
- Investigators
- David E Newby, DSc, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01674257
- Sponsor's protocol ID
- MICA-V1.3
- Other IDs
- PG/12/8/29371
- Acronym
- MICA
- Status last verified
- Apr 2024
- First submitted
- 23 Aug 2012
- Last updated
- 2 May 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigation of the Role of 18F-Sodium Fluoride and 18F-Flurodeoxyglucose PET CT and USPIO Enhanced MRI in Imaging Carotid Artery Inflammation and Mineralization.
- ClinicalTrials.gov ID
- NCT01674257
- Acronym / sponsor ID
- MICA / MICA-V1.3
- Conditions
- Atherosclerosis, Stroke
- Keywords
- Atherosclerosis, Stroke, Positron-emission tomography, Ferumoxytol, Magnetic resonance imaging, Genetics, Calcification, Inflammation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian, British Heart Foundation
- Study start
- 10 Oct 2012 (actual)
- Primary completion
- 30 Jun 2014 (actual)
- Study completion
- 31 Jul 2015 (actual)
- First posted
- 28 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hardening of the arteries (atherosclerosis) is a common disorder that causes heart attacks and strokes. PET CT and contrast-enhanced MRI scans are two new ways of assessing atherosclerosis. The investigators propose to perform PET CT and MRI scans on patients with hardening of the neck arteries due to undergo surgery to remove the hardened areas. The investigators will then be able to compare the hot spots found on these scans with what the investigators can see in the removed specimens under the microscope in the laboratory. This will give investigators insight into the value of PET CT and MRI as tools for assessing atherosclerosis. It will also provide the investigators with new information relating to the underlying processes that give rise to atherosclerosis and will pave the way for the future development of new treatments.
Detailed description
Hardening of the arteries (atherosclerosis) is a very common health problem that can lead to fatal or disabling heart attacks and strokes. On many levels, it remains an incompletely understood illness.
Until relatively recently, the only way of assessing the severity of, or risk posed by, atherosclerosis was to measure the degree to which it narrowed a particular blood vessel. This method only tells part of the story; he investigators now know that frequently the 'culprit area' of atherosclerosis that causes the heart attack or stroke does not necessarily result in narrowing of the blood vessel - i.e. if the investigators only measure narrowness the investigators will miss lots of 'bad' atherosclerosis. As such, there is a pressing need to identify more sophisticated techniques of assessing the disease in order that people who are at higher risk of heart attack or stroke can be identified early and offered appropriate preventative treatment.
Techniques that provide this extra information could also significantly shorten the time it takes to get new treatments and drugs to market by providing a faster and more cost-effective way of assessing these treatments early in their development. Furthermore, in exploring new techniques that reflect more accurately what is going on within atherosclerosis in the body, deeper insight into the condition will be gained. This will in turn lead to the development of new treatments.
PET/CT scans and USPIO (a kind of tracer) enhanced MRI scans are two such techniques that demonstrate particular promise. These scanning methods not only provide more information about the composition and architecture of the atherosclerosis but can provide data about the processes (at the chemical and cellular level) that underlie the disease.
Inflammation and calcification (deposits of calcium) are two biological processes that are known to be very important in the genesis of atherosclerosis. PET/CT and USPIO enhanced MRI can detect these processes.
Most strokes and mini-strokes are caused by a narrowing in the neck artery. If a patient with mini-stroke or stroke has a narrowing (atherosclerosis) in their carotid artery they are normally offered an operation to remove the atherosclerosis (endarterectomy), the piece of atherosclerosis is then normally discarded. This scenario affords a perfect opportunity to explore new scanning techniques.
The investigators propose to explore the feasibility and value of using PET/CT (using 18F-FDG and 18F-NaF - two tracers known to highlight inflammation and calcification) and USPIO enhanced MRI to assess atherosclerosis. The investigators will do this by scanning patients who have just had a mini-stroke or minor stroke and are due to undergo endarterectomy. The investigators will then be able to define what is going on at the level of the genes and the cells that causes 'hot spots' on CT/PET and MRI.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Carotid Endarterectomy | – | Other: USPIO (ferumoxytol)-enhanced MRI scan, Radiation: 18f-Fluoride PET/CT scan, Radiation: 18F-Flurodeoxyglucose PET/CT scanPatients due to undergo carotid endarterectomy for symptomatic carotid artery stenosis will undergo an 18F-Fluoride PET/CT, an 18F-Flurodeoxyglucose PET/CT and a USPIO (ferumoxytol)-enhanced MRI scan (2 MRI scans). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients referred for carotid endarterectomy for symptomatic carotid artery stenosis.
Key inclusion criteria (1 listed)
- Patients with carotid stenosis due to undergo carotid endarterectomy.
Key exclusion criteria (14 listed)
- Patients with new stroke and a modified Rankin score >3
- Chronic Kidney Disease with eGFR of <30 mL/min/1.73m2
- Pregnant women
- Poorly controlled diabetes mellitus (HbA1c > 8.5%) or diabetes mellitus requiring insulin
- Prior ipsilateral carotid intervention
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| USPIO (ferumoxytol)-enhanced MRI scanTwo separate MRI scans will form this intervention. A baseline scan followed by an infusion of USPIO (ferumoxytol), followed by another MRI scan. | Other | Carotid Endarterectomy |
| 18f-Fluoride PET/CT scan | Radiation | Carotid Endarterectomy |
| 18F-Flurodeoxyglucose PET/CT scan | Radiation | Carotid Endarterectomy |
Primary outcome
The Standardized Uptake Value (SUV) for 18F-Fluoride of the ipsilateral carotid artery
Time frame: 1-2 days after PET/CT scan
The mean and maximum SUV (using 18F-NaF) of the ipsilateral carotid artery will be calculated and compared to its contra lateral partner. The SUV is a validated quantitative assessment of PET radiotracer uptake.
8 secondary outcomes
The SUV of 18F-Flurodeoxyglucose on PET/CT of the ipsilateral carotid artery
Time frame: 1-2 days after PET/CT scan
A correlation between the ipsilateral carotid SUV of 18F-Flurodeoxyglucose and tissue markers of inflammation and apoptosis.
Time frame: Approximately 1 month after PET/CT scan
A correlation between ipsilateral carotid SUV of 18F-Fluoride and the gene expression characteristics of excised plaque.
Time frame: Approximately 1 month after the PET/CT scan
A correlation between the ipsilateral carotid SUV of 18F-Fluoride and tissue markers of apoptosis and calcification.
Time frame: Approximately 1 month after the PET/CT scan
The presence or absence of USPIO (ultra-small superparamagnetic particles of iron oxide) uptake on MRI (magnetic resonance image) within the ipsilateral carotid artery compared to its contralateral partner.
Time frame: 1-2 days after MRI scan
A correlation between the ipsilateral carotid USPIO uptake and tissue markers of inflammation and apoptosis.
Time frame: 1 month after MRI scan
A correlation between the ipsilateral carotid USPIO uptake and gene expression characteristics of excised atheroma.
Time frame: 1 month after the MRI scan
The ipsilateral carotid radioactivity, arterial blood radioactivity and whole blood fluoride concentration measured over time
Time frame: During the 18F PET/CT scan
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David E Newby, DSc principal investigator
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Atherosclerosis and Stroke, run by University of Edinburgh at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Standardized Uptake Value (SUV) for 18F-Fluoride of the ipsilateral carotid artery (time frame: 1-2 days after PET/CT scan). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2024.