Effect of Ketamine, Amitriptyline and Their Combination on Histaminergic and Non-histaminergic Itch
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Measuring itch by computerized Visual Analog Scale Scoring
研究概览
简要总结
Chronic itch affects approximately a fifth of the global population and is associated with substantial negative consequences for the affected individuals. Furthermore, there is a lack of efficient treat-ment options for chronic itch. Topical ketamine cream has been used successfully to relieve various forms of pain, and we hypothesize that topical ketamine relieves itch through a mechanism of action comparable to that in pain relief.
The aim of this project is to evaluate the effects of ketamine both alone and in combination with amitriptyline on histaminergic and non-histaminergic itch induced by histamine and cowhage, respectively.
详细描述
The main action of ketamine, 2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone, is to antagonize the glutamate N-methyl-D-aspartate (NMDA) receptors. In the clinical setting, topical ketamine cream has been used successfully to relieve various pathogenic forms of pain. In addition to its pain-relieving effects, the cream was also reported to have itch-relieving properties in a very limited study. However, its efficacy on itch has not been established, and the mechanism of action remains uncertain. Ketamine cream is used not only by itself, but also in conjunction with other analgesics. One of these is amitriptyline, which may enhance the analgesic effects of ketamine. The aim of this human experimental study is to use the well-characterized anesthetic Ketamine, both alone and in combination with amitriptyline, as a tool to modulate different histaminergic and non-histaminergic itch modalities evoked by histamine and cowhage.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
盲法说明
The participant will be blinded about which cream is applied.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy men and women
- •18-60 years
- •Speak and understand English
排除标准
- •Pregnancy or lactation
- •Drug addiction defined as any use of cannabis, opioids, or other drugs
- •Previous or current history of neurological, dermatological, immunological, musculoskeletal, cardiac disorder or mental illnesses (psychiatric diagnosis) that may affect the results (e.g., neuropathy, muscular pain in the upper extremities, anxiety, depression, schizophrenia etc.)
- •Moles, wounds, scars, or tattoos in the area to be treated or tested
- •Current use of medications that may affect the trial such as antihistamines and pain killers.
- •Participants had known allergy/discomfort to ketamine or amitriptyline
- •Skin diseases
- •Consumption of alcohol or painkillers 24 hours before the study days and between these
- •Acute or chronic pain and itch
- •Participation in other trials within 1 week of study entry (4 weeks in the case of pharmaceutical studies)
- •Lack of ability to cooperate
研究组 & 干预措施
Cream application
This subproject will be conducted in two sessions one week apart. Each session will last approximately 3 hours. In each forearm of the participant, two 4x4 cm areas will be selected as Area of Interest (AOI). In these selected areas, the four different creams will be applied in a randomized position for 1½ hours. After the cream removal, itch will be induced using histamine in one session and cowhage in the other session (the order of histamine and cowhage will be randomized). During the application of the substances, the itch/pain elicited will be monitored for 10 minutes using a VAS (Visual analog scale). After the removal of the substances, measurements of SBP, TP, MEI, MPT, MPS, and thermal sensitivity will be conducted.
干预措施: Ketamine 0.5% (Drug)
Cream application
This subproject will be conducted in two sessions one week apart. Each session will last approximately 3 hours. In each forearm of the participant, two 4x4 cm areas will be selected as Area of Interest (AOI). In these selected areas, the four different creams will be applied in a randomized position for 1½ hours. After the cream removal, itch will be induced using histamine in one session and cowhage in the other session (the order of histamine and cowhage will be randomized). During the application of the substances, the itch/pain elicited will be monitored for 10 minutes using a VAS (Visual analog scale). After the removal of the substances, measurements of SBP, TP, MEI, MPT, MPS, and thermal sensitivity will be conducted.
干预措施: Amitriptyline (Drug)
Cream application
This subproject will be conducted in two sessions one week apart. Each session will last approximately 3 hours. In each forearm of the participant, two 4x4 cm areas will be selected as Area of Interest (AOI). In these selected areas, the four different creams will be applied in a randomized position for 1½ hours. After the cream removal, itch will be induced using histamine in one session and cowhage in the other session (the order of histamine and cowhage will be randomized). During the application of the substances, the itch/pain elicited will be monitored for 10 minutes using a VAS (Visual analog scale). After the removal of the substances, measurements of SBP, TP, MEI, MPT, MPS, and thermal sensitivity will be conducted.
干预措施: ketamine + amitriptyline (Drug)
Cream application
This subproject will be conducted in two sessions one week apart. Each session will last approximately 3 hours. In each forearm of the participant, two 4x4 cm areas will be selected as Area of Interest (AOI). In these selected areas, the four different creams will be applied in a randomized position for 1½ hours. After the cream removal, itch will be induced using histamine in one session and cowhage in the other session (the order of histamine and cowhage will be randomized). During the application of the substances, the itch/pain elicited will be monitored for 10 minutes using a VAS (Visual analog scale). After the removal of the substances, measurements of SBP, TP, MEI, MPT, MPS, and thermal sensitivity will be conducted.
干预措施: Vehicle (Other)
Cream application
This subproject will be conducted in two sessions one week apart. Each session will last approximately 3 hours. In each forearm of the participant, two 4x4 cm areas will be selected as Area of Interest (AOI). In these selected areas, the four different creams will be applied in a randomized position for 1½ hours. After the cream removal, itch will be induced using histamine in one session and cowhage in the other session (the order of histamine and cowhage will be randomized). During the application of the substances, the itch/pain elicited will be monitored for 10 minutes using a VAS (Visual analog scale). After the removal of the substances, measurements of SBP, TP, MEI, MPT, MPS, and thermal sensitivity will be conducted.
干预措施: Histamine (Other)
Cream application
This subproject will be conducted in two sessions one week apart. Each session will last approximately 3 hours. In each forearm of the participant, two 4x4 cm areas will be selected as Area of Interest (AOI). In these selected areas, the four different creams will be applied in a randomized position for 1½ hours. After the cream removal, itch will be induced using histamine in one session and cowhage in the other session (the order of histamine and cowhage will be randomized). During the application of the substances, the itch/pain elicited will be monitored for 10 minutes using a VAS (Visual analog scale). After the removal of the substances, measurements of SBP, TP, MEI, MPT, MPS, and thermal sensitivity will be conducted.
干预措施: Cowhage (Other)
结局指标
主要结局
Measuring itch by computerized Visual Analog Scale Scoring
时间窗: Immediately after the intervention
We will ask the subjects to rate the sensation of itch on a 100 mm VAS scale ranging from 0 to 100 where 0 indicates "no itch" and 100 indicates "worst itch imaginable".
Measuring pain by computerized Visual Analog Scale Scoring
时间窗: Immediately after the intervention
We will ask the subjects to rate the sensation of pain on a 100 mm VAS scale ranging from 0 to 100 where 0 indicates "no pain" and 100 indicates "worst pain imaginable".
次要结局
- Superficial blood perfusion(Immediately after the intervention)
- Touch Pleasantness(Immediately after the intervention)
- Mechanically evoked itch (MEI), intensity approach(Immediately after the intervention)
- Mechanically evoked itch, spatial approach(Immediately after the intervention)
- Mechanical Pain Thresholds (MPT)(Immediately after the intervention)
- Mechanical Pain Sensitivity (MPS), intensity approach(Immediately after the intervention)
- Mechanical Pain Sensitivity (MPS), spatial approach(Immediately after the intervention)
- Cold Detection Thresholds (CDT)(Immediately after the intervention)
- Warm Detection Thresholds (WDT)(Immediately after the intervention)
- Cold Pain Thresholds (CPT)(Immediately after the intervention)
- Heat Pain Thresholds (HPT)(Immediately after the intervention)
- Pain to Supra-threshold Heat Stimuli (STHS)(Immediately after the intervention)
研究者
Silvia Lo Vecchio
Assistant Professor
Aalborg University