A Placebo-controlled, Single-blind, Cross-over, Randomised, fMRI Study Comparing Cue-induced Brain Activation Patterns After a Single Oral Dose of GSK598809 or Placebo in Abstinent Alcoholic Subjects
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- BOLD signal changes in the relevant brain areas following presentation of visual alcohol-related vs neutral, non-alcohol related cues.
研究概览
简要总结
This study will compare the effects of GSK598809 and placebo in alcohol dependent volunteers. A placebo is a pill with no drug in it (i.e. dummy drug) but it is made to look exactly like the real drug.
Subjects will be given one dose of GSK598809 during one visit and placebo during the other visit. These dosing visits will be at least 1 week apart. The study is randomised, which means that a computer programme will decide by chance (like tossing a coin), the order in which subjects will receive GSK598809 or the placebo, or in other words, whether they will receive GSK598809 or placebo first.
The study is blinded, which means the subjects will not know whether they are receiving study drug or placebo first and neither will the doctors at the institute. If necessary for reasons of safety, the study staff can find out exactly what the subject has received.
The study will last for approximately 4 weeks but could be up to 6 weeks, depending on length of time between screening and dosing. From screening the subjects will be alcohol-abstinent, they may be put on medication for treatment of withdrawal symptoms and then will have at least 7 days without any medication before beginning the study medication. During the study the subjects will be inpatients at the Central Institute of Mental Health. All subjects will be required to fill out questionnaires, perform behavioural tasks and undergo MRI and functional MRI (fMRI) scans.
详细描述
This is a randomised, placebo controlled, cross-over, single-blind study of the effects of GSK598809 (175 mg, single dose) on multiple pharmacodynamic measures assessed by fMRI and rating scales. In one period subjects will receive GSK598809 and in the other, placebo.
Investigator, subject and all staff at site involved with the study will remain blinded throughout the study. The GSK team will be unblinded to the randomisation code. GSK has classed this as a single blind study however as both investigator and subject are blinded it is referred to as double blind in the study design.
Twenty four recently detoxified and not currently on medication, alcohol-dependent subjects on a specialised addiction ward will be the study group. These subjects will be recruited into this study while participating in a intramural treatment program, outside of the protocol. Subjects will remain in the unit for the duration of the study.
Alcohol-dependent subjects who enter the institutes' treatment program will be screened between 28 and 15 days prior to the first dose of the study medication according to the eligibility criteria. Subjects who satisfy the inclusion and exclusion criteria will be entered into the study. Along with the study procedures described within this protocol, subjects will participate in the institutes standardized inpatient behavioral addiction treatment program outside of the protocol.
Alcohol-dependent participants have to fulfil diagnostic criteria of alcohol dependence as detailed in the eligibility criteria. The severity of alcoholism will be assessed with the Alcohol Dependence Scale and the amount of lifetime alcohol intake will be measured with Lifetime Drinking History.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Alcohol dependent for at least 2 years.
- •Willing to use appropriate contraception method.
- •Weight less than 120 kg.
- •BMI within the range 18.5 - 33 kg/m2.
排除标准
- •Heavy smokers (more than 25 cigarettes per day).
- •Liver cirrhosis.
- •Pregnant or breast feeding female.
- •Psychiatric disorder.
- •Substance dependence or abuse other than alcoholism and nicotine dependence.
- •Medical illness.
- •ECG abnormality (personal or family history).
- •Sudden unexplained death or syncope in first degree relative.
研究组 & 干预措施
Placebo
Placebo to match GSK598809.
干预措施: GSK598809 (Drug)
结局指标
主要结局
BOLD signal changes in the relevant brain areas following presentation of visual alcohol-related vs neutral, non-alcohol related cues.
时间窗: 1.5h (± 0.5h) after each dose (2 doses)
BOLD signal changes in the same brain structures and circuits as above during a Monetary Incentive Delay task.
时间窗: 1.5h (± 0.5h) after each dose (2 doses)
次要结局
- Pair-wise correlation of BOLD signal changes in different image voxels and between selected brain structures during the alcohol-related cue paradigm and the Monetary Incentive Delay task, and in the brain resting state.(1.5h (± 0.5h) after each dose (2 doses))
- Spontaneously reported adverse events, laboratory values, cardiovascular variables (blood pressure, heart rate, and ECG variables), temperature, respiratory rate, serum prolactin concentrations, TSH, testosterone, LH and FSH.(Throughout study.)
- Pharmacokinetic parameters of GSK598809 and its metabolite GSK685249: AUC (0-∞), Cmax, tmax, t½.(Pre-dose to 48h post dose.)
- Subjective craving in response to alcohol-related cues measured with the Alcohol Urge Questionnaire (AUQ) and the Obsessive Compulsive Drinking Scale (OCDS).(Screening and pre-scan.)