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

Itch Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03943407
• Other study ID #: N-20190029
• Status: Withdrawn
• Phase: N/A
• Start date: November 2019
• Est. completion date: June 2022

Study information

• Verified date: January 2021
• Source: Aalborg University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2022
• Est. primary completion date: June 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Healthy men and women

• 18-60 years

• 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

• Acute or chronic pain

• Participation in other trials within 1 week of study entry (4 weeks in the case of pharmaceutical trials)

Related Conditions & MeSH terms

• Itch

Intervention

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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Denmark	Aalborg University	Aalborg	Nordjylland

Sponsors (1)

Lead Sponsor	Collaborator
Aalborg University

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Superficial blood perfusion by by a Speckle contrast imager (FLPI, Moor Instruments, England).	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.	Change from baseline, to maximum 19 days after intervention
Primary	Trans-epidermal Water Loss (TEWL)	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.	Change from baseline, to maximum 19 days after intervention
Primary	Neurogenic Inflammatory Response and Pigmentation	treatment will be measured with a spectrometer designed for cutaneous use (ColorMeter, DSM II; Cortex Technology, Hadsund, Denmark).	Change from baseline, to maximum 19 days after intervention
Primary	Measuring Alloknesis	Alloknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).	Change from baseline, to maximum 19 days after intervention
Primary	Thermal measurements (cold and warm detection thresholds, cold and heat pain thresholds)	The tests for thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device	Change from baseline, to maximum 19 days after intervention
Primary	Measurement of Pain to Supra-threshold Heat Stimuli	The test will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device	Change from baseline, to maximum 19 days after intervention
Primary	Measurement of Mechanical Detection Thresholds, Mechanical Pain Threshold and sensitivity	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.	Change from baseline, to maximum 19 days after intervention
Secondary	Measurement of Itch rating by Computerized Visual Analog Scale Scoring	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.	Change from baseline, to maximum 19 days after intervention
Secondary	Measurement of pain rating by Computerized Visual Analog Scale Scoring	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.	Change from baseline, to maximum 19 days after intervention