VISION: Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography

Sponsor

University of Cambridge (Other)

Overall Status

Completed

CT.gov ID

NCT02021188

Collaborator

(none)

Enrollment

Location

Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This VISION study aims to investigate the role of inflammation in atherosclerosis using 68Ga- DOTATATE PET, and to validate 68Ga-DOTATATE PET imaging for the detection and quantification of vascular inflammation in the aorta, coronary and carotid arteries. This study will test the hypothesis that in subjects undergoing carotid endarterectomy for symptomatic plaques, there will be a positive correlation between carotid artery 68Ga-DOTATATE PET signal and the underlying degree of carotid inflammation measured by immunohistochemical analysis.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis Stroke Transient Ischemic Attack Chronic Stable Angina Acute Coronary Syndrome

Detailed Description

Clinical events in atherosclerosis are largely driven by inflammation. Molecular imaging of atherosclerosis can potentially identify high-risk lesions, help guide treatment and illuminate the underlying biology of the disease. 18F-fluorodeoxyglucose (18F-FDG) PET is the gold-standard nuclear molecular imaging technique with well-established roles in atherosclerosis imaging. However, the arterial 18F-FDG signal is non-specific, although it is related to increased macrophage activity with contributions from hypoxia and angiogenesis. Coronary artery imaging with 18F-FDG is particularly difficult, mainly due to high background myocardial cell 18F-FDG uptake, which obscures interpretation of the coronary signal. Efforts to suppress myocardial 18F-FDG uptake with dietary manipulation are challenging for patients and have limited efficacy.

PET tracers currently used in cancer imaging, such as 68Ga-DOTATATE, are potentially more specific for inflammation and also lack myocardial muscle uptake. 68Ga-DOTATATE might therefore be better suited than 18F-FDG for imaging inflammation, particularly within the coronary arteries. The VISION study is a prospective, observational study designed to investigate the biology of plaque inflammation in atherosclerosis, using PET imaging with the somatostatin receptor ligand 68Ga-DOTATATE. 50 subjects with atherosclerosis will undergo sequential PET/CT imaging with 68Ga-DOTATATE and 18F-FDG, along with contrast angiography of the carotid and coronary arteries. Autoradiography and immunohistochemistry of excised carotid plaques will be used to validate the imaging data. If successful, 68Ga-DOTATATE imaging will offer a cheaper, more specific non-invasive measure of inflammation than 18F- FDG, particularly in the coronary arteries. This opens up the possibility of better risk stratification for patients with atherosclerosis and could provide a non-invasive platform to test the effects of novel anti-atherosclerosis drugs.

Study Design

Study Type:

Observational

Actual Enrollment :

42 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

The Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography Study

Study Start Date :

Aug 1, 2014

Actual Primary Completion Date :

Aug 1, 2016

Actual Study Completion Date :

Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Carotid artery disease Participants with symptomatic or asymptomatic carotid artery plaques
Coronary artery disease Participants with stable coronary artery disease or recent acute coronary syndrome

Outcome Measures

Primary Outcome Measures

Correlation of 68Ga-DOTATATE PET signal to carotid plaque inflammation [Baseline]
This primary outcome measure is correlation between carotid artery 68Ga-DOTATATE PET signal (TBR) and the underlying degree of carotid inflammation, measured by CD68 immunohistochemistry, in patients undergoing carotid endarterectomy.

Secondary Outcome Measures

Comparison of 68Ga-DOTATATE signal between symptomatic and asymptomatic carotid plaques [Baseline (<1 month from event)]
Correlation of carotid artery and coronary artery 68Ga-DOTATATE uptake [Baseline]
Correlation of Framingham Cardiovascular Risk Scores to arterial 68Ga-DOTATATE uptake [Baseline]
Correlation between carotid artery 68Ga-DOTATATE autoradiographic signal and degree of carotid inflammation, measured by CD68 immunohistochemistry [Baseline]
Comparison of myocardial 68Ga-DOTATATE and 18F-FDG uptake [Baseline (2 scans within 1 week)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥40 years of age
Can provide written, fully informed consent
Have had a transient ischemic attack (TIA) or stroke within the preceding four weeks due to carotid artery atherosclerosis; or have ≥30% carotid artery or epicardial coronary artery stenosis

Exclusion Criteria:

Renal impairment (eGFR<30mls/min)
History of contrast nephropathy
Atrial fibrillation
Any condition, in the opinion of the investigator, which prevents the participant from lying flat during scanning
Women of childbearing potential
Inability to provide written informed consent
Haemorrhagic stroke within 3 months of study entry
Total occlusion of a culprit carotid artery
Any medical condition, vital sign or laboratory value that, in the opinion of the investigator, makes the subject ineligible for inclusion