Characterization of the Cytokine Profile and the Microbiome in Darier's Disease (DARKINBIOT)

December 5, 2024 updated by: University Hospital, Toulouse

Characterization of the Cytokine Profile and the Microbiome in Darier's Disease: Towards New Therapeutic Perspectives.

Darier disease is a rare genetic skin disease caused by mutations in the ATP2A2 gene. Clinically, patients present with inflammatory and keratotic papules, sometimes erosive and oozing, predominating in seborrheic areas and folds. The lesions are very visible, causing itching and pain and a significant impairment of quality of life. Complications such as superinfections of the skin (bacterial and viral) are very common and sometimes severe. Therapeutically, treatments are mainly symptomatic and often of limited effectiveness, particularly on inflammation and pruritus. The main objective of this clinical study is to compare the microbiota of the epidermis of patients with Darier disease in non-lesional areas versus lesional areas , making it possible to identify bacteria/clusters of bacteria, but also to analyze the metabolic pathways of the microbiota associated with the microbial signature, until now not described. The secondary objectives envisaged are to study the correlation between this microbiotic profile and both the clinical characteristics of patients and the cytokine profile. The research will be performed on 40 patients aged 18 or over, suffering from moderate to severe Darier Disease. For each patient, several samples will be collected including biopsies, blood sample, swabbing and tape-stripping, on lesional and non-lesional areas.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

A study carried out in 75 patients showed the presence of Staphylococcus aureus in lesional skin in 68% of cases, this percentage being correlated with the affected surface and the severity of the disease. Histologically, there is a characteristic appearance of acantholytic dyskeratosis and the underlying dermis is the site of inflammation. On the physiopathological level, the mutations cause disturbances in calcium metabolism, causing a loss of cell adhesion and a disruption of keratinocyte differentiation. The mechanisms leading to inflammatory skin lesions and frequent superinfections are poorly understood and could be the consequence of the abnormality of the skin barrier, causing disturbances in the cytokine profile and the microbiota.

This has been shown in hereditary ichthyoses, another group of diseases with keratinization disorders, in which microbiota abnormalities and a TH17 cytokine profile have been demonstrated.

In Darier disease, a study published in 2023 also showed the presence of a TH17 profile in 6 patients.

In 2 patients, clinical improvement was also noted when using biotherapy targeting interleukin 17 or 23. Also in 2023, Amar et al. studied the skin microbiota of 14 patients and showed the presence of Staphylococcus aureus and Staphylococcus warneri in the inflammatory areas, the abundance of which correlated with the severity of the disease.

Our study will provide additional data to this recent work, by highlighting differential cytokine and microbiota signatures between the two skin areas studied, in order to validate our hypothesis of the involvement of cytokines and the microbiota in chronic skin inflammation.

Study Type

Interventional

Enrollment (Estimated)

40

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 Contact

Study Contact Backup

Study Locations

  • France
    • Centre Hospitalier Universitaire de Toulouse
      • Toulouse, Centre Hospitalier Universitaire de Toulouse, France, 31059
        • Recruiting
        • University Hospital of Toulouse
        • Contact:
          • Juliette MAZEREEUW-HAUTIER
        • Contact:

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients aged 18 or over,
  • MD (clinical diagnosis),
  • MD moderate to severe,
  • Person affiliated or beneficiary of a social security scheme,
  • Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research).

Exclusion Criteria:

  • Other inflammatory dermatological diseases : atopic dermatitis, psoriasis and lichen planus,
  • Skin superinfection (clinical diagnosis),
  • Treatment with a biotherapy, in progress or in the 12 weeks preceding inclusion,
  • Treatment with oral retinoids introduced in the 6 months preceding inclusion,
  • Application of tacrolimus to the areas or to more than 30% of the body surface,
  • Application of topical corticosteroids to the areas or to more than 30% of the body surface, within 2 weeks preceding inclusion,
  • Oral corticosteroid therapy in the 2 weeks preceding inclusion,
  • Application of topical retinoids to the areas in the 2 weeks prior to inclusion,
  • Oral and/or topical antibiotic therapy in the 2 weeks preceding inclusion,
  • Local antiseptic in the 2 weeks preceding inclusion,
  • Local keratolytics on areas within 5 days preceding inclusion.

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: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: investigation : biopsy and blood extraction
Procedure: skin biopsies and blood extraction

Two 5 mm skin biopsies: lesional area and non-lesional area, on the trunk.

  • One blood sample (20 ml) to extract the plasma.
  • 15 successive tape-strippings in a lesional area.
  • Scans with two swabs: lesional area (preferably the trunk, 5 cm x 5 cm area) and non-lesional area.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of microbiotic profiles (genomes of microorganisms) in lesional and non-lesional areas.
Time Frame: day 1
Shotgun Metagenome Sequencing is used to learn what genomes are present in the sample
day 1

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterization qualitatively and quantitatively, at the epidermis level, the cytokine profile of patients (lesional skin, non-lesional skin)
Time Frame: Day 1
This is a proteomic analysis of the cells of the sample
Day 1
Correlation between the microbiotic profile observed on the epidermis (lesional skin) and the clinical characteristics of patients
Time Frame: Day 1
Analysis of the symptoms of the patient and observation of the microbiotic profile to observe if microbiotic profile corresponds to clinical symptoms.
Day 1
Comparison of the cytokine profile in the lesional area vs. non-lesional area, from the dermis (from a biopsy) of patients.
Time Frame: Day 1
Analysis of the cytokines in each biopsy
Day 1

Collaborators and Investigators

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

Sponsor

University Hospital, Toulouse

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France

Investigators

  • Principal Investigator: Juliette Mazereeuw-hautier, MD, University Hospital of Toulouse

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 4, 2024

Primary Completion (Estimated)

September 25, 2025

Study Completion (Estimated)

September 25, 2025

Study Registration Dates

First Submitted

August 26, 2024

First Submitted That Met QC Criteria

September 24, 2024

First Posted (Actual)

September 26, 2024

Study Record Updates

Last Update Posted (Estimated)

December 11, 2024

Last Update Submitted That Met QC Criteria

December 5, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC31/22/0509

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

product manufactured in and exported from the U.S.

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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