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Activation of a Cutaneous Inflammasome in the Skin of Hidradenitis Suppurativa Patients

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02833909
First Posted: July 14, 2016
Last Update Posted: July 18, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
CHU de Reims
  Purpose

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.


Condition Intervention
Hidradenitis Suppurativa Other: surgery

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: ex Vivo Study of the Inflammatory Response Associated With Hidradenitis Suppurativa

Resource links provided by NLM:


Further study details as provided by CHU de Reims:

Primary Outcome Measures:
  • cytokine quantification (IL1-β) by ELISA [ Time Frame: up to 4 days ]
  • cytokine quantification (IL-10) by ELISA [ Time Frame: up to 4 days ]
  • cytokines quantification (IL-13) by ELISA [ Time Frame: up to 4 days ]
  • cytokines quantification (IL-18) by ELISA [ Time Frame: up to 4 days ]
  • cytokines quantification (CXCL10) by ELISA [ Time Frame: up to 4 days ]
  • cytokines quantification (TNFα) by ELISA [ Time Frame: up to 4 days ]
  • cytokines quantification (TGFβ) by ELISA [ Time Frame: up to 4 days ]

Estimated Enrollment: 20
Study Start Date: March 2015
Study Completion Date: March 2016
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HS Other: surgery
Experimental: Controls Other: surgery

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.
  Eligibility

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02833909


Locations
France
Chu Reims
France, Reims, France, 51092
Sponsors and Collaborators
CHU de Reims
  More Information

Responsible Party: CHU de Reims
ClinicalTrials.gov Identifier: NCT02833909     History of Changes
Other Study ID Numbers: PO14129
First Submitted: July 4, 2016
First Posted: July 14, 2016
Last Update Posted: July 18, 2016
Last Verified: July 2016

Additional relevant MeSH terms:
Hidradenitis
Hidradenitis Suppurativa
Sweat Gland Diseases
Skin Diseases
Skin Diseases, Bacterial
Bacterial Infections
Skin Diseases, Infectious
Infection
Suppuration