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
  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 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: PET Imaging of Peripheral Benzodiazepine Receptors in Patients With Carotid Atherosclerosis

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Binding of [11C]PBR28 at peripheral benzodiazepine receptor [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PET [F-18]FDG uptake [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: October 2007
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: [C-11]PBR28
    N/A
Detailed Description:

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:   No
Criteria
  • 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.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00547976

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Suburban Hospital
Bethesda, Maryland, United States, 20814
Sponsors and Collaborators
  More Information

Publications:
Responsible Party: Robert B. Innis, M.D./National Institute of Mental Health, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00547976     History of Changes
Other Study ID Numbers: 080006, 08-M-0006
Study First Received: October 20, 2007
Last Updated: April 26, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Inflammation
Unstable Plaque
Macrophage
Thrombosis
Autoradiography
Atherosclerosis
Vasculitis

Additional relevant MeSH terms:
Atherosclerosis
Arteriosclerosis
Carotid Artery Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on October 19, 2014