The objective of this project is to assess the applicability of [11C]GMOM for in vivo imaging of the NMDA receptor.
ID
Source
Brief title
Condition
- Other condition
- Neurological disorders NEC
- Schizophrenia and other psychotic disorders
Synonym
Health condition
onderzoek heeft in de toekomst betrekking op bovenstaande aandoeningen, maar wordt uitgevoerd bij gezonde controles
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objectives:
i) To examine the regional brain uptake and its metabolites of [11C]GMOM in
healthy volunteers.
ii) To examine the specific binding potential of [11C]GMOM in the brain in
healthy volunteers before and after ketamine displacement
iii) To assess the whole body biodistribution and to determine the dosimetry of
[11C]GMOM in healthy volunteers.
Secondary outcome
not applicable
Background summary
Alterations in NMDA receptor function have been implicated in the
pathophysiology of several neurological and neuropsychiatric disorders, such as
schizophrenia and Alzheimer*s disease. In vivo imaging of the NMDA receptor
would be a valuable tool to assess the role of NMDA receptor availability in
the pathophysiology of neurological and neuropsychiatric disorders. [11C]GMOM
has excellent preclinical characteristics for this purpose and is suitable for
evaluation in human subjects.
Study objective
The objective of this project is to assess the applicability of [11C]GMOM for
in vivo imaging of the NMDA receptor.
Study design
This is an open study. The study consists of three substudies with three groups
of healthy subjects according to the three objectives. Both men and women are
allowed to participate in this study with the age range from 18 to 40 years
old. The first group (N=4, regional brain uptake and metabolites substudy)
will receive a dose of 370 Mega Becquerel (MBq) [11C]GMOM. If a signal in the
brain can be identified, the specific binding of [11C]GMOM in the brain will be
assessed in a second group of healthy volunteers (N=6) before and after
intravenous administration of S-ketamine (0.3 mg/kg).
The final group (N=4, biodistribution and dosimetry substudy) will receive a
standard dose of 370 MBq of [11C]GMOM to assess the whole body biodistribution
and to determine the effective dose of [11C]GMOM.
However, since first the expiration time of [11C]GMOM will be assessed, the
study will start with only three subjects from the first group. After scanning
these participants, permission will be asked from the medical ethical committee
of the VU University Medical Center to include more participants in the study
(see protocol section 3).
Study burden and risks
The benefit of this study is its contribution to the development of a novel
NMDA PET tracer. At present, there is no well validated NMDA receptor PET
radioligand available. This would provide a powerful means to examine NMDA
receptor aetiology in various patient groups with neurological and psychiatric
diseases, such as Alzheimer*s disease and schizophrenia. In addition, a novel
NMDA tracer will create the possibility for imaging-guided therapy.
Furthermore, a novel PET radiotracer that can target the NMDA receptor can
assess the mechanisms of drugs, which will be of high interest for the
development of novel pharmaceuticals. Risks associated with participation in
this study are related to radiation exposure, idiosyncratic reaction to the
tracer, placement of intra-venous and arterial catheters, blood sampling,
discomfort during scanning, and adverse events in response to ketamine
administration (only group 2 will receive ketamine, see also protocol section
8.2.3 and protocol section 10.3).
Hugo de Grootstraat 9
Utrecht 3581XR
NL
Hugo de Grootstraat 9
Utrecht 3581XR
NL
Listed location countries
Age
Inclusion criteria
- Men and women;
- Age between 18-40 years;
- Good physical health evaluated by medical history, physical (including neurological) examination and screening laboratory tests (Haemoglobin (Hb) must be 8 mmol \ litre at the time of the screening for males and 7 mmol \ litre for females);
- Weight 50 kg;
- Never mentally ill according to Research Diagnostic Criteria (RDC);
- A negative pregnancy test must be obtained for all females within 48 hours before starting the PET scan;- Normal MRI scan as evaluated by a neuroradiologist;
- Written informed consent of the subject;
Exclusion criteria
- (History of) Any psychiatric or neurological disorder (DSM-IV criteria);
- Coronary heart disease;
- (History of) Alcohol and/or drug abuse (DSM-IV criteria);
- Any clinical significant abnormality of any clinical laboratory test, including drug screening;
- Any condition that may interfere with MRI scanning, e.g. metal objects in or around the body or claustrophobia;
- Blood donation or substantial blood loss within 3 months before the PET scan;
- Intake of investigational medication within 30 days prior to the start of this study;
- Pregnancy;
- Smoking;
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-001521-27-NL |
| CCMO | NL37858.029.12 |