Darier DiseaseDARKINBIOTNCT06614777
Characterization of the Cytokine Profile and the Microbiome in Darier's Disease
A study testing skin biopsies and blood extraction in people with Darier Disease, run by University Hospital, Toulouse at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Darier Disease
- What is being tested?
- skin biopsies and blood extraction
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteFrance
- Study dates
- 4 Nov 2024to 25 Sep 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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,
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
University Hospital of Toulouse
Toulouse, Centre Hospitalier Universitaire de Toulouse, 31059
Nadege ALGANS, 0561777204, algans.n@chu-toulouse.fr
Juliette MAZEREEUW-HAUTIER
About this study
Official title: 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.
Read the 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.
- Conditions
- Darier Disease
- Being tested
- skin biopsies and blood extraction
- Keywords
- Darier disease, cytokine profil,, microbiome, proteomic analysis, targeting therapy
- Medical subject headings
- Darier Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
skin biopsies and blood extractionProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| investigation : biopsy and blood extraction | Experimental | Not described Receives: Procedure: skin biopsies and blood extraction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of microbiotic profiles (genomes of microorganisms) in lesional and non-lesional areas.
Shotgun Metagenome Sequencing is used to learn what genomes are present in the sample
Measured: day 1
Secondary outcomes (3)
Characterization qualitatively and quantitatively, at the epidermis level, the cytokine profile of patients (lesional skin, non-lesional skin)
This is a proteomic analysis of the cells of the sample
Measured: Day 1
Correlation between the microbiotic profile observed on the epidermis (lesional skin) and the clinical characteristics of patients
Analysis of the symptoms of the patient and observation of the microbiotic profile to observe if microbiotic profile corresponds to clinical symptoms.
Measured: Day 1
Comparison of the cytokine profile in the lesional area vs. non-lesional area, from the dermis (from a biopsy) of patients.
Analysis of the cytokines in each biopsy
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2024
- Study start4 Nov 2024
- Primary completion25 Sep 2025 (estimated)
- Study completion25 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Darier DiseaseStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Interventional study, exploratory, prospective, descriptive, bicentric.
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Juliette Mazereeuw-hautier, MD, Principal investigator, University Hospital of Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06614777
- Sponsor's protocol ID
- RC31/22/0509
- Acronym
- DARKINBIOT
- Status last verified
- Dec 2024
- First submitted
- 26 Aug 2024
- Last updated
- 11 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of the Cytokine Profile and the Microbiome in Darier's Disease: Towards New Therapeutic Perspectives.
- ClinicalTrials.gov ID
- NCT06614777
- Acronym / sponsor ID
- DARKINBIOT / RC31/22/0509
- Conditions
- Darier Disease
- Keywords
- Darier disease, cytokine profil,, microbiome, proteomic analysis, targeting therapy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France
- Study start
- 4 Nov 2024 (actual)
- Primary completion
- 25 Sep 2025 (estimated)
- Study completion
- 25 Sep 2025 (estimated)
- First posted
- 26 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Interventional study, exploratory, prospective, descriptive, bicentric.
| Arm | Type | Receives |
|---|---|---|
| investigation : biopsy and blood extraction | Experimental | Procedure: skin biopsies and blood extraction |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (11 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| skin biopsies and blood extractionTwo 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. | Procedure or surgery | investigation : biopsy and blood extraction |
Primary outcome
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
3 secondary outcomes
Characterization qualitatively and quantitatively, at the epidermis level, the cytokine profile of patients (lesional skin, non-lesional skin)
Time frame: Day 1
Correlation between the microbiotic profile observed on the epidermis (lesional skin) and the clinical characteristics of patients
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2024.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Juliette Mazereeuw-hautier, MD principal investigator
University Hospital of Toulouse
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing skin biopsies and blood extraction in people with Darier Disease, run by University Hospital, Toulouse at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nadège ALGANS, PM (0561777204, algans.n@chu-toulouse.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of microbiotic profiles (genomes of microorganisms) in lesional and non-lesional areas. (time frame: day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2024.