Metabolic Imaging in Carotid Atherosclerosis

NCT ID: NCT01674257

Last Updated: 2024-05-02

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 26 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-10-10
• Study Completion Date: 2015-07-31

Brief 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. 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.

Conditions

Atherosclerosis; Stroke

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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).

USPIO (ferumoxytol)-enhanced MRI scan

Intervention Type: OTHER

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 scan

Intervention Type: RADIATION

18F-Flurodeoxyglucose PET/CT scan

Intervention Type: RADIATION

Interventions

USPIO (ferumoxytol)-enhanced MRI scan

Two separate MRI scans will form this intervention. A baseline scan followed by an infusion of USPIO (ferumoxytol), followed by another MRI scan.

Intervention Type: OTHER

18f-Fluoride PET/CT scan

Intervention Type: RADIATION

18F-Flurodeoxyglucose PET/CT scan

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Patients with carotid stenosis due to undergo carotid endarterectomy.

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NHS Lothian

OTHER_GOV

Sponsor Role: collaborator

British Heart Foundation

OTHER

Sponsor Role: collaborator

University of Edinburgh

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David E Newby, DSc

Role: PRINCIPAL_INVESTIGATOR

University of Edinburgh

Locations

Clinical Research Imaging Centre

Edinburgh, , United Kingdom

Countries

United Kingdom

Other Identifiers

PG/12/8/29371

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

MICA-V1.3

Identifier Type: -

Identifier Source: org_study_id