- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02833909
Activation of a Cutaneous Inflammasome in the Skin of Hidradenitis Suppurativa Patients
ex Vivo Study of the Inflammatory Response Associated With Hidradenitis Suppurativa
The objective is to investigate ex vivo the inflammatory response in hidradenitis suppurativa (HS) (activation of an inflammasome, role of pro-inflammatory cytokines) in the skin of patients treated surgically for this disease.
The investigators hypothesize that Th17-derived cytokines, especially Interleukin (IL) IL-17, could serve as a relay in the inflammatory process leading to HS severity and recurrences.
Study Overview
Detailed Description
The objective is to investigate ex vivo the inflammatory response in hidradenitis suppurativa (activation of an inflammasome, role of pro-inflammatory cytokines) in the skin of patients treated surgically for this disease.
The investigators hypothesize that Th17-derived cytokines, especially IL-17, could serve as a relay in the inflammatory process leading to HS severity and recurrences.To fulfil this proposal, the investigators will aim at demonstrating and characterizing the presence of an inflammasome associated to HS disease - Hypothesis It is widely accepted that hyperkeratinisation and follicular occlusion originate infection thereof causing skin inflammation. The investigators here hypothesized that host-derived danger signals led to the release of inflammatory mediators such as IL-1β by activating an inflammasome structure.
The inflammasome is a molecular platform controlling the expression and the activation of IL-1β via different sensors. The proinflammatory cytokine IL-1β could subsequently lead to the recruitment and orientation of lymphocytes towards a Th17 subtype creating a feedback loop maintaining excessive tissue inflammation in HS.
If such a complex inflammatory process is present in HS, blocking both the bacterial-induced (IL-1 β) and the sterile-associated (IL-17) inflammation would largely improve the therapeutic benefit for HS patients.
- Experimental approach
The investigators will seek to highlight the presence of inflammasome sensors and effectors in skin explants from HS compared to control skin. For this original physiopathological study, 10 lesional skins excised from HS patients or controls (plastic surgery) after they signed informed consent as required by the ethical review board (CPP accepted on the 23-01-2015) will be investigated. HS disease severity will be based on staging according to Hurley staging. Six mm skin punches will be harvested from control explants and from both in situ and peri-lesional sites of HS skin explants. Skin samples will be handled either straight forwardly (day 0) or after a period of tissue culture of 4 days with or w/out treatments.
All experiments will be conducted as follows:
- Ex vivo skin tissue samples will be inserted in a Transwell® filter and cultured over a period of 4 days with or w/out antibiotics (Rifampicin, Clindamycin).
Both at day 0 and day 4:
- one set of skin samples will be embedded to analyze the presence of inflammasome sensors and effectors by immunohistochemistry (IHC)
- Another set will be homogenized for cytokines determination (ELISA) and cell stimulation (see below)
- Homogenized samples will be treated or not with anti-cytokine antibodies (Secukinumab vs isotype) for 4 hours before addition to keratinocytes cell line or monocyte/macrophage cell line. The influence of IL-17 and bacterial infection on inflammasome activation in these cell lines will be investigated as above described and associated with PCR technique.
Study Type
Enrollment
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Reims
-
France, Reims, France, 51092
- CHU Reims
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients with moderate to severe HS in the Dermatology department of Reims CHU, and eligible for surgery
- Patients accepting to participate to the study (signed consent)
- Patients affiliated to a certain social scheme
- Controls with plastic surgery but without HS, affiliated to a certain social scheme and accepting to participate
Exclusion Criteria:
- Patients <18yo
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: HS
|
|
Experimental: Controls
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
cytokine quantification (IL1-β) by ELISA
Time Frame: up to 4 days
|
up to 4 days
|
cytokine quantification (IL-10) by ELISA
Time Frame: up to 4 days
|
up to 4 days
|
cytokines quantification (IL-13) by ELISA
Time Frame: up to 4 days
|
up to 4 days
|
cytokines quantification (IL-18) by ELISA
Time Frame: up to 4 days
|
up to 4 days
|
cytokines quantification (CXCL10) by ELISA
Time Frame: up to 4 days
|
up to 4 days
|
cytokines quantification (TNFα) by ELISA
Time Frame: up to 4 days
|
up to 4 days
|
cytokines quantification (TGFβ) by ELISA
Time Frame: up to 4 days
|
up to 4 days
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PO14129
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.
Clinical Trials on Hidradenitis Suppurativa
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Yale UniversityNot yet recruitingHidradenitis Suppurativa | Hidradenitis Suppurativa, Acne Inversa | Hidradenitis Suppurativa \(HS\)United States
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Incyte CorporationRecruitingHidradenitis Suppurativa (HS)United States, Canada, Bulgaria, Italy, Spain, Germany, Poland, France, Australia, Denmark, United Kingdom
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-
Association pour la Recherche Clinique et ImmunologiqueNot yet recruitingHidradenitis Suppurativa (HS)France
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