Characterization of the Toll-like Receptor 7-agonist Imiquimod 3.75% As a New Surrogate Model of Itch
- Conditions
- Itch
- Interventions
- Other: HistamineOther: L-mentholOther: CowhageOther: Trans-cinnamaldehyde (CA)
- Registration Number
- NCT03943407
- Lead Sponsor
- Aalborg University
- Brief Summary
The aim of this research project is to design a new model of human itch by application of Zyclara cream. Further, the aim is to characterize the model and to verify if the mechanism of action of imiquimod follows the histaminergic or non-histaminergic pathway by using the anti-histamine drug doxepin. The last goal is to evaluate the interaction between the activation of TLR7 receptor and the activation of TRPA1 and TRPM8 receptors, which are two of the most important receptors involved in the transduction of noxious stimuli, and to evaluate to which extent these three channel populations functionally overlap.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- Healthy men and women
- 18-60 years
- Speak and understand English
- Pregnancy or lactation
- Drug addiction defined as any use of cannabis, opioids or other drugs
- Previous or current neurologic, musculoskeletal or mental illnesses
- Lack of ability to cooperate
- Current use of medications that may affect the trial
- Skin diseases
- Consumption of alcohol or painkillers 24 hours before the study days and between these
- Acute or chronic pain
- Participation in other trials within 1 week of study entry (4 weeks in the case of pharmaceutical trials)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Zyclara/vehicle Zyclara 3.75 % Topical Cream All subjects will be treated with Zyclara cream (Imiquimod 3.75%) and vehicle. Zyclara/Histamine/Cowage Cowhage All subjects will be treated with Zyclara cream, vehicle cream, histamine and cowhage Zyclara/Doxepin Zyclara 3.75 % Topical Cream All subjects will be treated with the topical antihistamine cream (Prudoxin, containing 5% doxepin hydrochloride, Healthpoint, San Antonio, TX) or a placebo cream. After removal, subjects will be treated with Zyclara cream Zyclara/Histamine/Cowage Zyclara 3.75 % Topical Cream All subjects will be treated with Zyclara cream, vehicle cream, histamine and cowhage Zyclara/Histamine/Cowage Histamine All subjects will be treated with Zyclara cream, vehicle cream, histamine and cowhage Zyclara/L-menthol/trans-cinnamaldehyde Zyclara 3.75 % Topical Cream All subjects will be treated with Zyclara cream (Imiquimod 3.75%) and vehicle. After removal, subjects will be treated with L/menthol and trans-cinnamaldehyde Zyclara/L-menthol/trans-cinnamaldehyde Trans-cinnamaldehyde (CA) All subjects will be treated with Zyclara cream (Imiquimod 3.75%) and vehicle. After removal, subjects will be treated with L/menthol and trans-cinnamaldehyde Zyclara/L-menthol/trans-cinnamaldehyde L-menthol All subjects will be treated with Zyclara cream (Imiquimod 3.75%) and vehicle. After removal, subjects will be treated with L/menthol and trans-cinnamaldehyde Zyclara/Doxepin Prudoxin All subjects will be treated with the topical antihistamine cream (Prudoxin, containing 5% doxepin hydrochloride, Healthpoint, San Antonio, TX) or a placebo cream. After removal, subjects will be treated with Zyclara cream
- Primary Outcome Measures
Name Time Method Superficial blood perfusion by by a Speckle contrast imager (FLPI, Moor Instruments, England). Change from baseline, to maximum 19 days after intervention Two pictures will be taken: one with the sensor placed approximately 35 cm above the induction area and one with the sensor placed approximately 20 cm above the induction area.
Trans-epidermal Water Loss (TEWL) Change from baseline, to maximum 19 days after intervention a 2x2 cm hollow probe with two small humidity gauges and two thermometers is placed lightly on the skin for 10-25 seconds. These establish a precise humidity gradient in a 2 cm vicinity of the skin, representative for the point-loss of water though the epidermis.
Neurogenic Inflammatory Response and Pigmentation Change from baseline, to maximum 19 days after intervention treatment will be measured with a spectrometer designed for cutaneous use (ColorMeter, DSM II; Cortex Technology, Hadsund, Denmark).
Measuring Alloknesis Change from baseline, to maximum 19 days after intervention Alloknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).
Thermal measurements (cold and warm detection thresholds, cold and heat pain thresholds) Change from baseline, to maximum 19 days after intervention The tests for thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Measurement of Pain to Supra-threshold Heat Stimuli Change from baseline, to maximum 19 days after intervention The test will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Measurement of Mechanical Detection Thresholds, Mechanical Pain Threshold and sensitivity Change from baseline, to maximum 19 days after intervention These tests are conducted using a set of 20 different von Frey hairs (North Coast Medical, Gilroy, CA) with exerted forces ranging from .008g to 300g.
- Secondary Outcome Measures
Name Time Method Measurement of Itch rating by Computerized Visual Analog Scale Scoring Change from baseline, to maximum 19 days after intervention We will ask the subjects to rate the sensation of itch on a VAS scale ranging from 0 to 10 where 0 indicates "no itch" and 10 indicates "worst itch imaginable"to 10 where 0 indicates "no itch" and 10 indicates "worst itch imaginable" and similarly for sensations of stinging/pricking and burning, both of which are frequently associated with the sensation of itch or pain.
Measurement of pain rating by Computerized Visual Analog Scale Scoring Change from baseline, to maximum 19 days after intervention the subjects will be asked to rate the sensation of pain on a VAS scale ranging from 0 to 10 where "0" is no pain and "10" is the worst pain.
Trial Locations
- Locations (1)
Aalborg University
🇩🇰Aalborg, Nordjylland, Denmark