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

NCT ID: NCT03943407

Last Updated: 2024-11-22

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-01
• Study Completion Date: 2022-06-30

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.

Conditions

Itch

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Zyclara/vehicle

All subjects will be treated with Zyclara cream (Imiquimod 3.75%) and vehicle.

Group Type: EXPERIMENTAL

Zyclara 3.75 % Topical Cream

Intervention Type: DRUG

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.

Zyclara/Doxepin

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

Group Type: EXPERIMENTAL

Zyclara 3.75 % Topical Cream

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Zyclara/Histamine/Cowage

All subjects will be treated with Zyclara cream, vehicle cream, histamine and cowhage

Group Type: EXPERIMENTAL

Zyclara 3.75 % Topical Cream

Intervention Type: DRUG

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.

Histamine

Intervention Type: OTHER

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

Intervention Type: OTHER

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.

Zyclara/L-menthol/trans-cinnamaldehyde

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

Group Type: EXPERIMENTAL

Zyclara 3.75 % Topical Cream

Intervention Type: DRUG

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.

L-menthol

Intervention Type: OTHER

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)

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: OTHER

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Aalborg University

OTHER

Sponsor Role: lead

Responsible Party

Silvia Lo Vecchio

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Aalborg University

Aalborg, North Denmark, Denmark

Countries

Denmark

Other Identifiers

N-20190029

Identifier Type: -

Identifier Source: org_study_id