Effects of an Anti-TRPM8 in the Atopic Dermatitis Pruritus

Not Applicable

Completed

• Conditions: Atopic Dermatitis
• Interventions: Other: No adding menthoxypropanediol to the biopsy; Other: Adding menthoxypropanediol to the biopsy

• Registration Number: NCT03610386
• Lead Sponsor: University Hospital, Brest

Brief Summary

The aim of the study is to analyse the effect of the menthoxypropanediol, a derivative of menthol, on the pruritus of atopic dermatitis (ex vivo study).

Detailed Description

AD is a fairly common pathology whose prevalence in Western Europe and the United States is estimated at 10 to 15% in children and 4 to 7% in adults. This frequency has been steadily increasing for several decades. However, while the prevalence is increasing rapidly in emerging countries, a plateau has been observed for a few years in the industrialized countries with a maximum of 20% reached in Northern Europe.

The predominant symptom of AD is pruritus. It has a strong impact on the lives of patients both physically, psychologically and socially, which causes stress and sleep disorders. Because of this pruritus, sleep disturbances but also the displaying character of the disease, the quality of life of patients and their families is very often altered.

The pathophysiology of this chronic pathology and associated pruritus is complex and incompletely understood and current treatments are unfortunately only symptomatic.

Many receptors (TRPA1, TRPV1, PAR2 ...), molecules (neuromediators, neuropeptides, histamine ...) and secreted cytokines (IL-2, -4, -13 and -31, TSLP) are involved in the induction and mediation of chronic pruritus. Their role in pruritus associated with AD begins to be understood. Among them, the TRPM 8 has a particular interest. Indeed, this receptor belongs to the superfamily of the "potential transient receptor (TRP)" whose members are known to play a major role in sensory perceptions, including the perception of pruritus. TRPM8 is a thermoreceptor, activated by cold (T \<28 ° C) or compounds such as menthol or derivatives, or eucalyptus and the beneficial action of menthol in the soothing of pruritus makes the TRPM8 receptor an attractive therapeutic target for treatment of pruritus in AD. Its role has never been studied in this context.

This project aims to study the role of TRPM8 in the pathophysiology of pruritus in AD in an in vitro model. Biopsies of atopic dermatitis patients (2/patient in pruritic skin lesion) will be put in culture and submit to topical application of menthoxypropanediol. The effect of this molecule on receptors involved in pruritus pathway will be assay (immunohistochemistry, QPCR).

Study Timeline

• Study First Submitted: 2018-06-12
• Study First Submitted QC: 2018-07-31
• Study First Posted: 2018-08-01
• Study Start: 2018-11-21
• Primary Completion: 2019-01-29
• Study Completion: 2019-01-29
• Status Verified: 2021-12
• Last Update Submitted: 2021-12-10
• Last Update Posted: 2021-12-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Patients over 18 years of age with atopic dermatitis.
• AND presenting active itchy lesions,
• Patients with no systemic and / or topical treatment for AD or pruritus.
• Patients who gave their written consent

Exclusion Criteria

• Patients with a physical or psychological disability to sign the consent.
• Patients not supported by social security.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	No adding menthoxypropanediol to the biopsy	Two biopsies of skin (4 mm diameter each) will be taken under local anesthetic in the service of dermatology of Brest CHRU. They will be situated in a pruritic lesion area little or not visible (inside of the arm, the back ...).One of two biopsies will be left in culture for 24 hours and then the biopsy will be cut in half: half will be used for immunohistochemical analyzes, the second half for transcriptomic analyzes .
Treatment with menthoxypropanediol	Adding menthoxypropanediol to the biopsy	Two biopsies of skin (4 mm diameter each) will be taken under local anesthetic in the service of dermatology of Brest CHRU. Thy will be situated in a pruritic lesion area little or not visible (inside of the arm, the back ...).One of two biopsies will be left in culture for 24 hours. Then the menthoxypropanediol (200 µM) will be applied topically on this explant and left for 6 hours. Then the biopsy will be cut in half: half will be used for immunohistochemical analyzes, the second half for transcriptomic analyzes.

Primary Outcome Measures

Name	Time	Method
Mitigation of pruritus markers after topical application of menthoxypropanediol on AD skin biopsies : proteins expression analysis	ONE DAY	For proteins expression analysis, Immunostaining of specific receptors and proteins will be made on skin sections of AD skin biopsy. Photos will be realized with an "Axiocam" camera and analyzed by "Axiovision" software. Staining intensity of each will be evaluated in well-defined reference areas by quantitative (immuno-)histomorphometry by using ImageJ software. Relative intensity of each receptor or protein of AD patient biopsy treated or not by menthoxypropanediol will be compared to each other and compared also to healthy skin.
Mitigation of pruritus markers after topical application of menthoxypropanediol on AD skin biopsies : transcriptomic analysis	ONE DAY	For transcriptomic analysis, RNA from AD skin biopsies will be extracted and QPCR analysis will be performed. Variation of receptor and proteins expression with and without menthoxypropanediol treatment will be realized on AD skin and also compared to healthy skin.

Trial Locations

Locations (1)

CHU Brest; 🇫🇷 Brest, France