Human Cold Pain - a Single-group, Randomized, Placebo-controlled, Adaptive, Factorial Crossover Trial
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- AUC Pain3°C
研究概览
简要总结
Animal studies suggest that the transient receptor potential ion channels TRPM8 and TRPA1 are cold sensors and that sodium channels Nav1.8 and Nav1.7 are essential for detecting pain induced by cold temperatures. This study aims to validate these findings in humans.
详细描述
It is essential for human survival to be able to perceive potentially harmful cold. The perception of slight cooling in animals depends on the ion channel TRPM8, but this may represent a largely separate mechanism from painful cold. In mice, TRPM8 and TRPA1 appear to be involved, but also the sodium channels Nav1.7 and Nav1.8, through their temperature-dependent function. These receptors might be redundant, so that failure of individual receptors only leads to no or only a partial reduction in the detection of cold.
Since results obtained in animals do not always translate to humans, the investigators want to clarify whether TRPM8, TRPA1, Nav1.7 and Nav1.8 are involved in the perception of cold pain in humans.
In order to induce cold pain experimentally, an increasingly cooled solution (down to 3°C) is injected into the skin, and the inhibitors for the mentioned targets are added individually and in combination.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 18 and 70 years
- •Full legal capacity
- •To ensure an equal number of each sex in the study population, only volunteers of one sex will be included as soon as the number of subjects with the other sex has reached half of the calculated sample size.
排除标准
- •Participant of another study, ongoing or within the last 4 weeks
- •Medication intake (except contraception) or drug abuse
- •Female subjects: Positive pregnancy test or breastfeeding
- •Body temperature above 38°C, diagnostically verified
- •Known allergic diseases, in particular asthmatic disorders and skin diseases
- •Sensory deficit, skin disease or hematoma of unknown origin in physical examination of the test site
研究组 & 干预措施
Room temperature injection
Pain induced by intradermal injection of fluid with room temperature.
干预措施: Room temperature (Other)
Cold temperature injection 1
Pain induced by intradermal injection of increasingly cold fluid down to 3°C.
干预措施: Cold temperature (Other)
Cold temperature injection with lidocain
Pain induced by intradermal injection of increasingly cold fluid down to 3°C including lidocain (unspecific sodium channel blocker).
干预措施: Cold temperature (Other)
Cold temperature injection with lidocain
Pain induced by intradermal injection of increasingly cold fluid down to 3°C including lidocain (unspecific sodium channel blocker).
干预措施: Lidocain (Drug)
Cold temperature injection 2
Pain induced by intradermal injection of increasingly cold fluid down to 3°C.
干预措施: Cold temperature (Other)
Cold temperature injection with PF-05105679
Pain induced by intradermal injection of increasingly cold fluid down to 3°C including PF-05105679 (specific TRPM8 antagonist).
干预措施: Cold temperature (Other)
Cold temperature injection with PF-05105679
Pain induced by intradermal injection of increasingly cold fluid down to 3°C including PF-05105679 (specific TRPM8 antagonist).
干预措施: PF-05105679 (Drug)
Cold temperature injection with A-967079
Pain induced by intradermal injection of increasingly cold fluid down to 3°C including A-967079 (specific TRPA1 antagonist).
干预措施: Cold temperature (Other)
Cold temperature injection with A-967079
Pain induced by intradermal injection of increasingly cold fluid down to 3°C including A-967079 (specific TRPA1 antagonist).
干预措施: A967079 (Drug)
Cold temperature injection with PF-05089771
Pain induced by intradermal injection of increasingly cold fluid down to 3°C including PF-05089771 (specific Nav1.7 antagonist).
干预措施: Cold temperature (Other)
Cold temperature injection with PF-05089771
Pain induced by intradermal injection of increasingly cold fluid down to 3°C including PF-05089771 (specific Nav1.7 antagonist).
干预措施: PF-05089771 (Drug)
Cold temperature injection with PF-06305591
Pain induced by intradermal injection of increasingly cold fluid down to 3°C including PF-06305591 (specific Nav1.8 antagonist).
干预措施: Cold temperature (Other)
Cold temperature injection with PF-06305591
Pain induced by intradermal injection of increasingly cold fluid down to 3°C including PF-06305591 (specific Nav1.8 antagonist).
干预措施: PF-06305591 (Drug)
Cold temperature injection with PF-05105679, A-967079, PF-05089771, PF-06305591
Pain induced by intradermal injection of increasingly cold fluid down to 3°C including PF-05105679 (TRPM8)-, A-967079 (TRPA1)-, PF-05089771 (Nav1.7)-, PF-06305591 (Nav1.8)- antagonist.
干预措施: Cold temperature (Other)
Cold temperature injection with PF-05105679, A-967079, PF-05089771, PF-06305591
Pain induced by intradermal injection of increasingly cold fluid down to 3°C including PF-05105679 (TRPM8)-, A-967079 (TRPA1)-, PF-05089771 (Nav1.7)-, PF-06305591 (Nav1.8)- antagonist.
干预措施: PF-05105679 (Drug)
Cold temperature injection with PF-05105679, A-967079, PF-05089771, PF-06305591
Pain induced by intradermal injection of increasingly cold fluid down to 3°C including PF-05105679 (TRPM8)-, A-967079 (TRPA1)-, PF-05089771 (Nav1.7)-, PF-06305591 (Nav1.8)- antagonist.
干预措施: A967079 (Drug)
Cold temperature injection with PF-05105679, A-967079, PF-05089771, PF-06305591
Pain induced by intradermal injection of increasingly cold fluid down to 3°C including PF-05105679 (TRPM8)-, A-967079 (TRPA1)-, PF-05089771 (Nav1.7)-, PF-06305591 (Nav1.8)- antagonist.
干预措施: PF-05089771 (Drug)
Cold temperature injection with PF-05105679, A-967079, PF-05089771, PF-06305591
Pain induced by intradermal injection of increasingly cold fluid down to 3°C including PF-05105679 (TRPM8)-, A-967079 (TRPA1)-, PF-05089771 (Nav1.7)-, PF-06305591 (Nav1.8)- antagonist.
干预措施: PF-06305591 (Drug)
结局指标
主要结局
AUC Pain3°C
时间窗: Through study completion, on average 90 minutes.
The primary outcome variable is the area under the curve (AUC) of pain ratings over a limited duration of the infusion period, i.e. from 120-150 seconds (last 30 seconds of the cold stimulus).
次要结局
- AUC Pain(Through study completion, on average 90 minutes.)
研究者
Stefan Heber
Principal Investigator
Medical University of Vienna