A PET Study in Healthy Volunteers
Study Details
Study Description
Brief Summary
This will be an open label, non-randomised [11C]PHNO PET study using healthy male volunteers. Each volunteer will undergo 4 [11C]PHNO PET scans to allow for further characterisation of this radioligand and examine the effects of [11C]PHNO mass carry-over and displaceable binding in the brain. This study aims to obtain data from 6 evaluable subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 1 |
Detailed Description
A test-retest (TRT) investigation of [11C]PHNO in human is required to further characterise [11C]PHNO. [11C] PHNO possesses very high affinity for the D3 receptor, and therefore most clinical studies are conducted at D3 occupancies >10%. As [11C]PHNO kinetics in the target brain regions are moderately slow, considerable mass carry over may be present on a 2nd PET scan conducted on the same day. In addition there appears to be a significant displaceable binding component in the cerebellum, which, if not accounted for, will lead to a bias in the quantification of specific [11C]PHNO binding. The aim of this study is therefore to examine the effects of [11C]PHNO mass carry-over and displaceable binding in the cerebellum, on the quantification of [11C]PHNO PET data.
This will be an open label, non-randomised [11C]PHNO PET study using healthy volunteers. Each volunteer will undergo 4 [11C]PHNO PET scans:
1st and 2nd scans; TRT on the same day with a minimal gap between [11C]PHNO injections to examine the effects of PHNO mass carry over, 3rd scan >1 week later to determine the "true" TRT variability and a 4th scan will follow a 15mg dose of aripiprazole (a D2/D3 compound which allows the highest clinically acceptable blockade of central D2/D3 receptors) and will examine the amount of displaceable binding in the cerebellum, a proposed reference tissue for [11C]PHNO.
The scan data will be quantified as regional volumes of distribution (VT).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: no treatment Aripiprazole is a D2/D3 antagonist registered in the UK for use in the treatment of schizophrenia. It allows the highest clinically acceptable blockade of central D2/D3 receptors and will allow us to examine the amount of displaceable binding in the brain - a proposed reference tissue for [11C]PHNO. |
Radiation: [11C]PHNO
examine the effects of [11C]PHNO mass carry-over and displaceable binding
Drug: Aripiprazole
A 4th scan will follow a 15mg dose of aripiprazole (a D2/D3 compound which allows the highest clinically acceptable blockade of central D2/D3 receptors)
|
Outcome Measures
Primary Outcome Measures
- volume of distribution [one year]
Regional volume of distribution (VT) in sub-cortical, brainstem and cerebellar regions of interest at each PET scan.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Healthy as determined by a responsible physician
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Male subjects between 25 and 55 years of age.
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Male subjects must agree to use one of the contraception methods listed
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Capable of giving written informed consent
Exclusion Criteria:
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The subject has a positive pre-study drug/alcohol screen
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The subjects is using or has used regular prescription or non-prescription drugs
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Current or recent (within one year) gastrointestinal disease
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A screening ECG with a QTc value of >450msec and/or a PR interval outside the range 120 to 200msec or an ECG that is not suitable for QT measurements
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Pulse rate <50 or >100 bpm OR a systolic blood pressure >140 or <100 OR a diastolic blood pressure >90 or <60.
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History of long QT syndrome (personal or family) or other cardiac conduction disorder, or other clinically significant cardiac disease.
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Any previous or current psychiatric diagnosis listed in DSM-IV Axis I or II
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Any history of suicidal attempts, suicidal ideation or behaviour as assessed by appropriately trained study personnel.
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History of alcohol dependence
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The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
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Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
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History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
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Where participation in the study would result in donation of blood or blood products in excess of 550 mL within a 56 day period.
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Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations with significant radiation burden
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Family history of cancer
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History of claustrophobia or subjects feeling that he will be unable to lie still on his back in the PET camera for a period of ~2 hours at a time.
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History or presence of a neurological diagnosis
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Presence of a cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies as assessed by a standard pre-MRI questionnaire.
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Unwillingness or inability to follow the procedures outlined in the protocol. -
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | London | United Kingdom | W12 ONN |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 113549