A Positron Emission Tomography Study in Healthy Male Subjects to Examine the Test-retest Reliability of the D2/3 Agonist Radiotracer [11C]PHNO
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- volume of distribution
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 盲法
- None
入排标准
- 年龄范围
- 22 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy as determined by a responsible physician
- •Male subjects between 25 and 55 years of age.
- •Male subjects must agree to use one of the contraception methods listed
- •Capable of giving written informed consent
排除标准
- •The subject has a positive pre-study drug/alcohol screen
- •The subjects is using or has used regular prescription or non-prescription drugs
- •Current or recent (within one year) gastrointestinal disease
- •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
- •Pulse rate <50 or >100 bpm OR a systolic blood pressure >140 or <100 OR a diastolic blood pressure >90 or <
- •History of long QT syndrome (personal or family) or other cardiac conduction disorder, or other clinically significant cardiac disease.
- •Any previous or current psychiatric diagnosis listed in DSM-IV Axis I or II
- •Any history of suicidal attempts, suicidal ideation or behaviour as assessed by appropriately trained study personnel.
- •History of alcohol dependence
- •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).
- •Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- •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.
- •Where participation in the study would result in donation of blood or blood products in excess of 550 mL within a 56 day period.
- •Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations with significant radiation burden
- •Family history of cancer
- •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.
- •History or presence of a neurological diagnosis
- •Presence of a cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies as assessed by a standard pre-MRI questionnaire.
- •Unwillingness or inability to follow the procedures outlined in the protocol. -
研究组 & 干预措施
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.
干预措施: [11C]PHNO (Radiation)
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.
干预措施: Aripiprazole (Drug)
结局指标
主要结局
volume of distribution
时间窗: one year
Regional volume of distribution (VT) in sub-cortical, brainstem and cerebellar regions of interest at each PET scan.
次要结局
未报告次要终点