Normal Binding of R-[11C]PK11195 in Human Subjects - Full Text View

Sponsored by:	VU University Medical Center
Information provided by:	VU University Medical Center
ClinicalTrials.gov Identifier:	NCT00205595

Purpose

This is a study using Positron Emission Tomography (PET) to study the normal distribution of the PET ligand (R)-[11C]PK11195. This ligand will be used to study inflammation in the brain in several brain disorders like Alzheimer's disease and traumatic brain injury.

Condition	Intervention	Phase
Normal Aging	Device: Positron Emission Tomography	Phase I

Drug Information available for: PK 11195

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Diagnostic, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics Study
Official Title:	The Distribution and Quantification of Specific Binding of the Positron Emission Tomography Tracer R)-[11C]PK11195 in Normal Human Subjects

Further study details as provided by VU University Medical Center:

Primary Outcome Measures:

specific binding of tracer depending on age

Secondary Outcome Measures:

tracer kinetic method

Estimated Enrollment:	40
Study Start Date:	February 2001
Estimated Study Completion Date:	January 2007

Detailed Description:

At the University Hospital Vrije Universiteit the PET ligand PK11195 labeled with carbon-11, (R)-[11C]PK11195, will be used to study microglia activation in-vivo in patients with traumatic brain damage, Alzheimer disease, multiple sclerosis and neuritis optica, disorders with unknown pathophysiology and treatment difficulties.

PK11195 (1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl)-3 isoquinolinecarboxamide) is a highly specific ligand for the peripheral benzodiazepine-binding site, which is particularly abundant on cells of the mononuclear macrophage line (Myers et al., 1991). In normal human brain, the peripheral-type benzodiazepine receptor ligand PK11195 exhibits low to minimal binding primarily associated with the choroid plexus, ependymal linings and glial cells. However, following neuronal damage, the cells involved in the ensuing gliosis, microglia, show a marked increase in expression of these sites (Stephenson et al., 1995;Conway et al., 1998).

PK11195 labeled with carbon-11 is a PET ligand to peripheral type benzodiazepine receptors which has already been used in patients with stroke (Ramsay et al., 1992), Rasmussen's encephalitis (Banati et al., 1999), multiple sclerosis (Banati et al., 1997) and facial nerve lesions (Myers et al., 1999). However, no tracer kinetic model for quantification has been fully validated for(R)-[11C]PK11195. In order to use (R)-[11C]PK11195 for PET-imaging of microglia activation and to use it in the longitudinal monitoring of disease progression, baseline levels of ligand uptake in a healthy control population are required. This study aims to measure (R)-[11C]PK11195 uptake in normal brain in different age groups and to develop methods for quantification of specific binding of (R)-[11C]PK11195. Because (R)-[11C]PK11195 uptake depends on regional bloodflow, each (R)-[11C]PK11195 scan will be preceded by a cerebral bloodflow scan with H215O.

OBJECTIVES

Determine the distribution of (R)-[11C]PK11195 in normal brain
Develop methods for quantification of specific binding of (R)-[11C]PK11195
Determine the metabolic profile of (R)-[11C]PK11195 in healthy volunteers

DESIGN OF THE STUDY Forty healthy subjects will be recruited, 20 males and 20 females. This is an open study. The study consists of one PET scan, which will be performed at the Department of Nuclear Medicine & PET research of the VU University Medical Centre.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Male and female subjects
Good physical and mental Health which will be evaluated with medical history, a physical examination and screening laboratory tests (see appendix 1).
Age between 18 and 40 years (20 subjects) and between 40 and 80 years (20 subjects).
Mini Mental State score >27
Body Mass Index (B.M.I.) between 20 -25.
Written informed consent of the subject.
Hb must be >8 mmol \ liter at the time of the screening.

Exclusion Criteria:

Previous neurotrauma with loss of consciousness
Any clinical significant abnormality of any clinical laboratory test, including drug screening, or ECG abnormality.
History of hypertension
Any subject who has received any investigational medication within 30 days prior to the start of this study, or who is scheduled to receive an investigational drug.
History of psychiatric or neurological illness
History of psychiatric or neurological illness in first-degree relatives
History of alcohol and/or drug abuse (DSM-IV criteria)
Current use of any medication
Blood donation within 3 months before the scan day
Claustrophobia
Metal objects in or around the body (braces, pacemaker, metal fragments);

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00205595

Locations

Netherlands
VU University Medical Centre
Amsterdam, Netherlands, 1081 HV

Sponsors and Collaborators

VU University Medical Center

Investigators

Principal Investigator:

Bart van Berckel, MD; PhD

VUmc Medical Centre

More Information

Study ID Numbers:	2001/001, no other ID's
Study First Received:	September 12, 2005
Last Updated:	July 3, 2008
ClinicalTrials.gov Identifier:	NCT00205595
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by VU University Medical Center:

microglia
PET
PK11195

Study placed in the following topic categories:

PK 11195

Additional relevant MeSH terms:

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009