Effects of an Anti-TRPM8 in the Atopic Dermatitis Pruritus (DA-TRPM8)

December 10, 2021 updated by: University Hospital, Brest

In Vitro Study Of the Effects of the Menthoxypropanediol, an Anti-TRPM8, in the Atopic Dermatitis Pruritus

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Brest, France
        • Chu Brest

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Control
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 .
Other: 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 the two biopsies will not receive menthoxypropanediol.
Experimental: Treatment with menthoxypropanediol
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.
Other: 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 the two biopsies will receive menthoxypropanediol topically.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mitigation of pruritus markers after topical application of menthoxypropanediol on AD skin biopsies : proteins expression analysis
Time Frame: 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.
ONE DAY
Mitigation of pruritus markers after topical application of menthoxypropanediol on AD skin biopsies : transcriptomic analysis
Time Frame: 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.
ONE DAY

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Brest

Collaborators

Beiersdorf

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 21, 2018

Primary Completion (Actual)

January 29, 2019

Study Completion (Actual)

January 29, 2019

Study Registration Dates

First Submitted

June 12, 2018

First Submitted That Met QC Criteria

July 31, 2018

First Posted (Actual)

August 1, 2018

Study Record Updates

Last Update Posted (Actual)

December 28, 2021

Last Update Submitted That Met QC Criteria

December 10, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DA-TRPM8 (29BRC18.0077)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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