Effects of Gaba-a-Agonists on Pain Mechanisms: An Experimental Study in Healthy Volunteers
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- area of hyperalgesia on the forearm
研究概览
简要总结
The investigators will use an intradermal capsaicin injection in the forearm to induce a state of localized pain. This localized pain will be measured by different means, and analysed locally and distally by so called quantitative sensory testing. The primary endpoint of measure is the difference in pain perception with and without benzodiazepines/GABA-Agonists around the injection point of capsaicin. The secondary endpoints are to measure pain modulation locally and distally by different quantitative tests as electricity, pressure pain thresholds, and ice water tests.
The investigators' hypothesis is that clobazam induces higher pain thresholds as placebo and less sedation than the control medication clonazepam.
详细描述
Background
Neuropathic and nociceptive pain are linked to plastic changes of the central nervous system. These lead to lower pain thresholds. An important component of this neuronal plasticity is a diminished inhibition-control of the neurons on the level of the spine, where an alpha-3 subunit of the glycine receptor plays an important role. Modulation of this receptor subunit with specific and non-specific GABA-Agonists produce antinociception. The new fact is, that a subunit specific medication does not induce sedation in animals. The relationship of pain modulation and Gaba-Agonists is not well studied in humans. The benzodiazepine used in pain therapy in humans is clonazepam, which induces a strong sedation, reason why it is not much used in a chronic pain setting. Clobazam is another GABA-Agonist, which is less sedative. To our knowledge its effects on pain modulation has never been studied in humans.
Objective
The aim is an analysis and description of clobazam on the central pain mechanisms. We will use well known quantitative sensory testing methods therefore.
The primary objective is to gather data about potential clinical use of clobazam in pain therapy. The secondary aim would be to do the same tests on new specific alpha-3 agonists, which are being developed by pharmaceutical industry.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •European males
- •18-55 years old
- •non smoking status or less than 10 cigarettes per day
- •no disease
- •Exclusion Criteria
- •any medication
- •any drug abuse
- •diseases of any type
排除标准
- 未提供
研究组 & 干预措施
1
干预措施: clobazam (Drug)
1
干预措施: clonazepam (Drug)
1
干预措施: tolterodine (Drug)
2
干预措施: clobazam (Drug)
2
干预措施: clonazepam (Drug)
2
干预措施: tolterodine (Drug)
3
干预措施: clobazam (Drug)
3
干预措施: clonazepam (Drug)
3
干预措施: tolterodine (Drug)
结局指标
主要结局
area of hyperalgesia on the forearm
时间窗: 11.2010
次要结局
- Diffuse noxious inhibition control(11.2010)
- Pressure cuff algometry(11.2010)
- pressure pain(11.2010)
- electrical stimulation-temporal summation(11.2010)
- psychomotor testing(11.2010)
- Pharmacokinetic study: plasmatic concentration measured in regular intervals with blood samples, starting at time zero and ending at time plus 24h after drug administration.(11.2010)
- Pharmacodynamic study: Measurement of pharmacodynamic behaviour of our 3 tested substances in relation to sedation score.(11.2010)
- Pharmacogenetic study: Measurement of subtype cytochrome P450 CYP3A4 and CYP2C19 by metabolites of midazolam and omeprazol. Genotyping of cytochrome P450 CYP3A4 and CYP 2C19.(11.2010)