PET Imaging of Peripheral Benzodiazepine Receptors in Patients With Carotid Atherosclerosis

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00547976
First received: October 20, 2007
Last updated: April 26, 2012
Last verified: April 2012

October 20, 2007
April 26, 2012
October 2007
August 2009   (final data collection date for primary outcome measure)
Binding of [11C]PBR28 at peripheral benzodiazepine receptor [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Binding of [11C]PBR28 at peripheral benzodiazepine receptor
Complete list of historical versions of study NCT00547976 on ClinicalTrials.gov Archive Site
PET [F-18]FDG uptake [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
PET Imaging of Peripheral Benzodiazepine Receptors in Patients With Carotid Atherosclerosis
PET Imaging of Peripheral Benzodiazepine Receptors in Patients With Carotid Atherosclerosis

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
  • Atherosclerosis
  • Healthy
Drug: [C-11]PBR28
N/A
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
5
August 2009
August 2009   (final data collection date for primary outcome measure)
  • INCLUSION CRITERIA

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.

Both
18 Years to 89 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00547976
080006, 08-M-0006
Not Provided
Robert B. Innis, M.D./National Institute of Mental Health, National Institutes of Health
National Institute of Mental Health (NIMH)
Not Provided
Not Provided
National Institutes of Health Clinical Center (CC)
April 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP