GABAergic Modulation in Pain Transmission in Human: Effect of the GABAA Agonist Clobazam on Peripheral and Central Sensitisation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Determination of the impact of clobazam on the change in the area of secondary hyperalgesia (in cm2) mapped with a Von Frey filament (256mN).
研究概览
简要总结
In animal, the GABAergic system modulates central sensitisation, which is a key phenomenon in pain processing. The development of GABAA agonists targeting the subunits of the GABAA receptor implicated in nociception, but not the subunit implicated in sedation is attractive as it opens new perspectives of testing the role of GABAergic modulation of pain processing in human volunteers. The purpose of this subproject is to test the effect of the specific α2 and α3 agonist but sparing α1 effect TPA023 on a human model of peripheral and central sensitisation and to correlate its pharmacodynamic effect with the pharmacokinetic of the compound.
The results would contribute to clarify the potential role of these α2/α3 agonist but sparing α1drugs in clinical pain conditions.
详细描述
Objectives:
- To assess the effect of the GABAA agonist clobazam on central sensitisation (change in the size of the area of secondary hyperalgesia) in healthy volunteers.
- To assess the effect of the GABAA agonist clobazam on peripheral sensitisation.
- To assess the effect of the GABAA agonist clobazam on sedation.
- To correlate the pharmacokinetic of clobazam to its effect (PK-PD modelling)
- To describe the role of the polymorphisms of CYP450 2C19 in the pharmacokinetic and dynamic of clobazam.
Methodology :
phase II , exploratory, three arms randomised placebo-controlled, double blind cross-over study in healthy volunteers
Number of patients : 25
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male subject, age between 18 and 60 year old
- •Caucasian
- •Type 3 skin phototype
- •Non smoker or moderate smoker (< 10 cigarettes/day)
- •No clinically abnormal findings on history and/or on physical examination
- •Presence of an area of secondary hyperalgesia after UVB irradiation
排除标准
- •Any concomitant illness
- •Current or past history of drug and alcohol abuse or current intake of more than 3 glasses of alcohol a day or more than 21 glasses of alcohol per week
- •Psychotropic drug intake during the last month
- •Sun allergy or any skin disease
- •Current and regular intake of any drugs that might affect nociception Paracetamol, or NSAIDS with a short half lives are permitted but should be stopped at least 48 h before the UVB session
研究组 & 干预措施
clobazam
干预措施: clobazam (Drug)
clonazepam
干预措施: Clonazepam (Drug)
tolterodine
干预措施: Tolterodine (Drug)
结局指标
主要结局
Determination of the impact of clobazam on the change in the area of secondary hyperalgesia (in cm2) mapped with a Von Frey filament (256mN).
时间窗: 3 single days spaced out with at least two weeks wash-out periods
次要结局
- Change in the pain threshold (heat (°C) static mechanical (g) and dynamic mechanical (Numerical rating scale NAS) in the area of secondary hyperalgesia(3 single days spaced out with at least two weeks wash-out periods)
- Change in the pain threshold (heat (°C ) static mechanical (g) and dynamic mechanical (NAS)) in the area of primary hyperalgesia(3 single days spaced out with at least two weeks wash-out periods)
- Change in Nociceptive Flexion Reflex(3 single days spaced out with at least two weeks wash-out periods)
- Change in the latency and in the area under the pain intensity/time curve in cold pressor test(3 single days spaced out with at least two weeks wash-out periods)
- Change in mean target saccades peak velocity, target saccades acceleration and deceleration, in saccade latency (msec), in saccadic accuracy, in smooth pursuit lead time and in the number of saccadic intrusions in the smooth pursuit.(3 single days spaced out with at least two weeks wash-out periods)
- Change in the total number and in the correct number of symbols drawn in the DDST challenge.(3 single days spaced out with at least two weeks wash-out periods)
- Time concentration curve evaluation: blood samples at 0,5, 1, 2, 4, 6, 8,12, and at 24 hours post-dose(3 single days spaced out with at least two weeks wash-out periods)
- Pharmacokinetic/ pharmacodynamic modelling.(3 single days spaced out with at least two weeks wash-out periods)
研究者
Jules Desmeules
MD
University Hospital, Geneva