Metabolic Imaging in Carotid Atherosclerosis (MICA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by University of Edinburgh
Sponsor:
Collaborators:
NHS Lothian
British Heart Foundation
Information provided by (Responsible Party):
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT01674257
First received: August 23, 2012
Last updated: March 5, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention
Atherosclerosis
Stroke
Other: USPIO (ferumoxytol)-enhanced MRI scan
Radiation: 18f-Fluoride PET/CT scan
Radiation: 18F-Flurodeoxyglucose PET/CT scan

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
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.

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • The Standardized Uptake Value (SUV) for 18F-Fluoride of the ipsilateral carotid artery [ Time Frame: 1-2 days after PET/CT scan ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • The SUV of 18F-Flurodeoxyglucose on PET/CT of the ipsilateral carotid artery [ Time Frame: 1-2 days after PET/CT scan ] [ Designated as safety issue: No ]
    The mean and maximum SUV (using 18F-Flurodeoxyglucose) of the ipsilateral carotid artery will be calculated and compared to its contra lateral partner.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    USPIOs are known to accumulate within activated macrophages in inflamed atheroma. This causes a demonstrable drop in T2* signal on MR.

  • A correlation between the ipsilateral carotid USPIO uptake and tissue markers of inflammation and apoptosis. [ Time Frame: 1 month after MRI scan ] [ Designated as safety issue: No ]
    Sections of excised atheroma will be co-stained for USPIO and a variety of immunohistochemical markers of inflammation and apoptosis.

  • A correlation between the ipsilateral carotid USPIO uptake and gene expression characteristics of excised atheroma. [ Time Frame: 1 month after the MRI scan ] [ Designated as safety issue: No ]
    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.

  • The ipsilateral carotid radioactivity, arterial blood radioactivity and whole blood fluoride concentration measured over time [ Time Frame: During the 18F PET/CT scan ] [ Designated as safety issue: No ]
    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.


Biospecimen Retention:   Samples With DNA

Blood and excised carotid atheroma


Estimated Enrollment: 60
Study Start Date: January 2013
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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).
Other: 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.
Radiation: 18f-Fluoride PET/CT scan Radiation: 18F-Flurodeoxyglucose PET/CT scan

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients referred for carotid endarterectomy for symptomatic carotid artery stenosis.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01674257

Contacts
Contact: Alex T Vesey, MB/ChB 00447795634522 avesey@staffmail.ed.ac.uk
Contact: David E Newby, DSc D.E.Newby@ed.ac.uk

Locations
United Kingdom
Clinical Research Imaging Centre Recruiting
Edinburgh, United Kingdom, EH16 4TJ
Contact: Alex T Vesey, MB/ChB    00447795634522    avesey@staffmail.ed.ac.uk   
Principal Investigator: Alex T Vesey, MB/ChB         
Sponsors and Collaborators
University of Edinburgh
NHS Lothian
British Heart Foundation
Investigators
Principal Investigator: David E Newby, DSc University of Edinburgh
  More Information

No publications provided

Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT01674257     History of Changes
Other Study ID Numbers: MICA-V1.3, PG/12/8/29371
Study First Received: August 23, 2012
Last Updated: March 5, 2013
Health Authority: United Kingdom: National Health Service

Keywords provided by University of Edinburgh:
Atherosclerosis
Stroke
Positron-emission tomography
Ferumoxytol
Magnetic resonance imaging
Genetics
Calcification
Inflammation
Flurodeoxyglucose F18
Radiopharmaceuticals

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Arterial Occlusive Diseases
Cardiovascular Diseases
Vascular Diseases
Ferrosoferric Oxide
Fluorides
Cariostatic Agents
Hematinics
Hematologic Agents
Parenteral Nutrition Solutions
Pharmaceutical Solutions
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014