Effects of High-concentration Topical Capsaicin on Histaminergic and Non-histaminergic Itch

Study Overview
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Brief Summary
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The purpose of this project is to investigate the effect of capsaicin-induced neurogenic inflammation with three different intensities on itch subsequently induced by histamine and cowhage. The hypothesis is that capsaicin-induced pre-established neurogenic inflammation significantly increases susceptibility to itch provocations with cowhage and histamine.

Official Title
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The Role of Pre-established Skin Inflammation on the Susceptibility to Histamine and Cowhage-induced Itch in Healthy Humans

Conditions
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Pruritus

Intervention / Treatment
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* Drug: Capsaicin 24 Hours
* Drug: Capsaicin 1 Hour
* Other: Qutenza Demo Patch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men and women 18-60 years Caucasian descent Speak and understand English Exclusion Criteria: 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 Moles or tattoos in the area to be irradiated Exposure of the irradiated area to UV radiation (e.g., sun) 48 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cowhage<br>Cowhage is used to induce non-histaminergic itch on the volar forearm at the locations treated with Capsaicin 24 Hours, Capsaicin 1 Hours and Qutenza Demo Patch. | Drug: Capsaicin 24 Hours<br>* Dermal patches for transdermal application of Capsaicin, applied for 24 hours<br>* Other names: Qutenza;Drug: Capsaicin 1 Hour<br>* Dermal patches for transdermal application of Capsaicin, applied for 1 hour<br>* Other names: Qutenza;Other: Qutenza Demo Patch<br>* Dermal patches mimicking active Qutenza patches. Used as control in comparison of Capsaicin efficacy. Applied for 24 hours.<br>* Other names: Qutenza Demo;|
| Other: Histamine<br>Histamine is used to induce histaminergic itch on the volar forearm at the locations treated with Capsaicin 24 Hours, Capsaicin 1 Hour and Qutenza Demo Patch. | Drug: Capsaicin 24 Hours<br>* Dermal patches for transdermal application of Capsaicin, applied for 24 hours<br>* Other names: Qutenza;Drug: Capsaicin 1 Hour<br>* Dermal patches for transdermal application of Capsaicin, applied for 1 hour<br>* Other names: Qutenza;Other: Qutenza Demo Patch<br>* Dermal patches mimicking active Qutenza patches. Used as control in comparison of Capsaicin efficacy. Applied for 24 hours.<br>* Other names: Qutenza Demo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Itch intensity | Rating of the perceived itch intensity on a visual analogue scale (VAS) App (Aalborg University) as displayed on a tablet computer with a sample rate of 1 Hz. | Assessed continuously at 0-10 minutes following itch provocation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurogenic inflammation | Neurogenic inflammation in the treated area is assessed using full-field laser perfusion imaging (FLPI) | Assessed 11 minutes after itch provocation | 
| Changes in sensitivity to touch-evoked itch | Three von Frey filaments are applied to the test area before and after itch provocation. Subjects report three NRS scores ('0-10', 'No itch-Worst imaginable itch') for itch induced by von Frey stimulation. Change is calculated by subtracting baseline mean from post-provocation mean NRS scores. | Assessed before, and at 12-15 minutes following itch provocation | 
| Wheal size | Histamine wheal size is assessed by measuring the longest diameter of the wheal with a ruler, followed by measuring the orthogonal diameter. The mean of these diameters will represent the wheal size in diameter, reported in mm. | Assessed at 10 minutes following itch provocation | 
| Pain intensity | Rating of the perceived pain intensity on a visual analogue scale (VAS) App (Aalborg University) as displayed on a tablet computer with a sample rate of 1 Hz. | Assessed continuously at 0-10 minutes following itch provocation | 
| Pain during capsaicin application | Peak and average numerical rating scale (NRS) scores ('0-10, 'no pain-worst imaginable pain') are reported by subjects for each patch. | 24 hours after first application of capsaicin patch |