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

Hidradenitis Suppurativa Clinical Trial

Official title:

ex Vivo Study of the Inflammatory Response Associated With Hidradenitis Suppurativa

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02833909
• Other study ID #: PO14129
• Status: Completed
• Phase: N/A
• First received: July 4, 2016
• Last updated: July 15, 2016
• Start date: March 2015
• Est. completion date: March 2016

Study information

• Verified date: July 2016
• Source: CHU de Reims
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Hidradenitis
• Hidradenitis Suppurativa

Intervention

Other:
• surgery

Locations

Country	Name	City	State
France	Chu Reims	France	Reims

Sponsors (1)

Lead Sponsor	Collaborator
CHU de Reims

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	cytokine quantification (IL1-ß) by ELISA		up to 4 days	No
Primary	cytokine quantification (IL-10) by ELISA		up to 4 days	No
Primary	cytokines quantification (IL-13) by ELISA		up to 4 days	No
Primary	cytokines quantification (IL-18) by ELISA		up to 4 days	No
Primary	cytokines quantification (CXCL10) by ELISA		up to 4 days	No
Primary	cytokines quantification (TNFa) by ELISA		up to 4 days	No
Primary	cytokines quantification (TGFß) by ELISA		up to 4 days	No