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| Sponsored by: |
National Institute of Mental Health (NIMH) |
|---|---|
| Information provided by: | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00547976 |
Purpose
Inflammation in the vascular wall is important in atherosclerosis and the blockage of the artery. The peripheral benzodiazepine receptor is involved in inflammation and in this protocol we will attempt to take pictures, using PET camera, of inflammation in patients with atherosclerosis and compare those of healthy people.
| Condition | Intervention | Phase |
|---|---|---|
|
Atherosclerosis Healthy |
Drug: [C-11]PBR28 |
Phase I Phase II |
| Study Type: | Interventional |
| Study Design: | Diagnostic, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Pharmacokinetics Study |
| Official Title: | PET Imaging of Peripheral Benzodiazepine Receptors in Patients With Carotid Atherosclerosis |
| Estimated Enrollment: | 60 |
| Study Start Date: | October 2007 |
Objective
Inflammation in the vascular wall plays an important role in the pathophysiology of atherosclerosis, including development of plaque, plaque destabilization and rupture. Clinical and basic scientific data demonstrate the importance of peripheral white blood cells in this process. Therefore, a noninvasive method to detect inflammatory activity in atherosclerosis may be of great value to help determine prognosis, direct therapy and perhaps assess novel therapies for stabilization of atherosclerotic plaque.
The peripheral benzodiazepine receptor (PBR) is distinct from central benzodiazepine receptors associated with GABAA receptors and has been associated with immune function. PBR is expressed in macrophages, therefore, they may be a clinically useful marker to detect inflammation. Our preliminary autoradiographic data demonstrate specific PBR binding in carotid atherosclerosis samples. Though PBR has been imaged in vivo with positron emission tomography (PET) using [(11)C]1-(2-chlorophenyl-N-methylpropyl)-3-isoquinoline carboxamide (PK11195), we developed a new ligand, [(11)C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine (PBR28) that shows greater specific signal than [(11)C]PK11195 in non-human primates.
The objective of this protocol is to assess the utility of [(11)C]PBR28 PET to detect inflammation in unstable atherosclerosis plaques and large vessels with inflammation.
Study population
Twenty patients with carotid atherosclerosis, 20 patients with large vessel vasculitis including Takayasu's and Giant Cell arteritis, and 20 age-matched healthy subjects will have one PET scan.
Design
A [(11)C]PBR28 PET scan and a [18 F] fluorodeoxyglucose (FDG) PET scan will be performed in patients with carotid atherosclerosis. If the patient has endarterectomy after the PET scan, endarterectomy samples will be evaluated by in vitro autoradiography using [3H]PK 11195 and immunohistological staining with macrophage markers. Patients with large vessel vasculitis and healthy subjects will also have a [(11)C]PBR28 PET scan [18 F]FDG PET scan.
Outcome measures
Binding of [(11)C]PBR28 in atherosclerotic lesions, aortic arch and its branches will be compared with the binding in the contralateral carotid artery and those in healthy subjects. Binding of [(11)C]PBR28 will also be compared with accumulation of [18 F]FDG in each region. In addition, if the patients with atherosclerosis have endarterectomy, the binding in the atherosclerotic lesions will be compared with immunohistological staining of macrophage markers.
Eligibility| Ages Eligible for Study: | 18 Years to 89 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Age 18 - 89
Ability to provide written informed consent
EXCLUSION CRITERIA
Severe systemic disease based on history, physical examination or laboratory tests that would prevent participation in the study
Prior participation in other research protocols in the last year such that radiation exposure would exceed the annual guideline of RSC
Pregnancy and breast feeding
Claustrophobia
Inability to lie flat for a few hours for the PET scans
Medically unstable
The blood glucose level is greater than 150 mg/dL after fasting
Any other condition which in the opinion of the PI would prevent satisfactory participation in and completion of the study.
Contacts and Locations| Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
| Contact: TTY | 1-866-411-1010 |
| United States, Maryland | |
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
More Information
| Responsible Party: | National Institutes of Health ( Robert B. Innis, M.D./National Institute of Mental Health ) |
| Study ID Numbers: | 080006, 08-M-0006 |
| Study First Received: | October 20, 2007 |
| Last Updated: | January 23, 2009 |
| ClinicalTrials.gov Identifier: | NCT00547976 History of Changes |
| Health Authority: | United States: Federal Government |
|
Inflammation Unstable Plaque Macrophage Thrombosis |
Autoradiography Atherosclerosis Vasculitis |
|
Arterial Occlusive Diseases Atherosclerosis Vasculitis Vascular Diseases Central Nervous System Diseases Healthy |
Arteriosclerosis Brain Diseases Carotid Artery Diseases Cerebrovascular Disorders Thrombosis Inflammation |
|
Arterial Occlusive Diseases Atherosclerosis Nervous System Diseases Vascular Diseases Central Nervous System Diseases |
Cardiovascular Diseases Arteriosclerosis Brain Diseases Carotid Artery Diseases Cerebrovascular Disorders |
