NCT03943407

Characterization of the Toll-like Receptor 7-agonist Imiquimod 3.75% As a New Surrogate Model of Itch

• Status: Withdrawn
• Phase: N/A
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Aalborg University · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

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.

Conditions

• Itch

Interventions

Type	Name	Description
DRUG	Zyclara 3.75 % Topical Cream	The cream will be applied on 4x4 cm squared areas on the volar forearm. The cream will be left in place for 2h, 1 h or 30 min (sub-study 1) after which it will be removed. The technical and security procedures will be conducted in accordance with the manufacturer's instructions.
DRUG	Prudoxin	The anti-histamine cream Prudoxin, containing 5% doxepin hydrochloride (1 g contains 50 mg of doxepin) (Healthpoint, San Antonio, TX) will be applied on the volar forearm. Two adhesive patches 4×4 cm (1mm thick, 3M foam adhesive tape, 3M, St. Paul, MN) each with a 3.5×3.5 cm center cut out (to deposit 1.2 grams of cream) will be each placed 3 cm distal and 3 cm proximal to the center of the volar aspect of each arm. Each patch will be covered with Tegaderm I.V., an occlusive, adhesive dressing (3M), for at least 1 h and 30 minutes.
OTHER	Histamine	To deliver histamine, standard allergy skin prick test (SPT) lancets are applied. The lancets have a 1 mm shouldered tip adapt to introduce a small amount of test substance extremely locally and approximately at the dermo-epidermal junction. . A small drop of histamine dihydrochloride (1%, in saline) will be applied to a previously determined area on the volar forearm followed by a prick through the drop.
OTHER	Cowhage	Cowhage spicules are 1-2 mm in length and have diameter of 1-3 um at their tip. The active substance delivered (mucunain) has been calculated to be in the nanogram range. The insertion of cowhage spicule(s) rapidly and consistently produces itch with no or very little flare reaction. This insertion is conducted by forceps using a stereo-microscope, and 30-35 spicules are gently rubbed into a 1 cm diameter skin area.
OTHER	L-menthol	L-menthol (≥99.9%, TRPM8 agonist; (Sigma Aldrich, Broendby, Denmark) is dissolved in 96% ethanol at concentrations of 40%(w/v) L-menthol. A 1 mL aliquot is dispensed onto a 3 × 3 cm cotton pad and placed on a 6 × 6 cm sheet of medical tape. In between the cotton pad and the medical tape, a layer of parafilm will be added to avoid evaporation. This configuration was subsequently applied for 1 h.
OTHER	Trans-cinnamaldehyde (CA)	CA will be obtained from Sigma Aldrich (Brøndby, Denmark) and dissolved in 90% ethanol at a concentration of 10% (vol/vol) CA. One ml aliquot of CA is dispensed onto a 3x3 cm cotton pad and placed on a 5x5 cm sheet of medical tape. Between the cotton pad and the tape, a layer of plastic film will be added to inhibit the evaporation of the solutions. This configuration will be applied for 1 h.

Timeline

• Start date: 2019-11-01
• Primary completion: 2021-06-01
• Completion: 2022-06-01
• First posted: 2019-05-09
• Last updated: 2024-11-22

Locations

1 site across 1 country: Denmark