Characterization and Functionality of Calcium Channels Cav1.4 of Th17 Lymphocytes in Human With Psoriasis

Not Applicable

Completed

• Conditions: Psoriasis
• Interventions: Biological: Skin biopsies; Biological: Blood sample

• Registration Number: NCT04459780
• Lead Sponsor: Pierre Fabre Dermo Cosmetique

Brief Summary

It's clearly known that lymphocyte activation in particular Th17 response, plays a major role in the development of plaque psoriasis. New therapies targeting this pathway are showing great clinical efficacy in patients with moderate to severe plaque psoriasis.

Pioneering observations have shown that the expression of Cav1.4 channels in Th17 lymphocytes and they're functional role is supported by the inhibition of IL-17 production by a pharmacological inhibitor of Cav1 channels that is effective in a mouse model of Psoriasis.

This data strongly suggest that the Cav1.4 channel, via its involvement in the signalling responsible for the production of Th17 cytokines represents an interesting therapeutic target in Psoriasis.

The aim of the study is to explore biological functions related to the activation of the Cav1.4 pathway in Psoriasis.

Detailed Description

* Evaluate the expression of Cav1.4 calcium channels by Th17 lymphocytes from plaque psoriasis.

* To assess:

* The role of Cav1.4 channels on the activation of Th17 lymphocytes

* The transcriptomic signature relating to the signalling channel Cav1.4

* The epigenetic signature, in particular changes in overall methylation and specific promoter methylation

Study Timeline

• Study Start: 2016-10-25
• Primary Completion: 2017-11-13
• Study Completion: 2017-11-13
• Status Verified: 2020-07
• Study First Submitted: 2020-07-01
• Study First Submitted QC: 2020-07-06
• Study First Posted: 2020-07-07
• Last Update Submitted: 2020-07-10
• Last Update Posted: 2020-07-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 40

Inclusion Criteria

• Group 1 : Subject with plaque psoriasis (diagnosis confirmed by dermatologist) with a plaque IGA score ≥ 3
• Group 2 : Subject with atopic dermatitis according to the UK Working party criteria with an IGA plaque score ≥3

Exlusion Criteria:

• Group 1 : Other chronic inflammatory dermatosis than plaque psoriasis at the sites to be sampled
• Group 2 : Other chronic inflammatory dermatosis than Atopic Dermatitis at the sites to be sampled
• For both groups: Ongoing treatment with calcium channel blockers
• For both groups: Any current topical treatment on the biopsied or systemic plaque for psoriasis or AD (including phototherapy)

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 : 20 subjects with plaque psoriasis	Skin biopsies	Intervention: skin biopsies and blood sample
Group 2 : 10 subjects with atopic dermatitis	Skin biopsies	Intervention: skin biopsies
Group 1 : 20 subjects with plaque psoriasis	Blood sample	Intervention: skin biopsies and blood sample

Primary Outcome Measures

Name	Time	Method
Expression of Cav1.4 calcium channels in Th17 lymphocytes	Baseline	Immunohistochemistry (IHC) and in situ hybridation (HIS)

Secondary Outcome Measures

Name	Time	Method
Role of Cav1.4 channels on the activation of Th17 lymphocytes	Baseline	Fonctional study : intracellular marquing and qPCR (with TLDA technology (TaqMan Low Density Arrrays)) and ELISA method
Transcriptomic signature relating to the signaling channel Cav1.4	Baseline	qPCR with TLDA technology (TaqMan Low Density Arrrays)
Epigenetic signature, in particular changes in overall methylation and specific promoter methylation	Baseline	Pyrosequencing

Trial Locations

Locations (1)

Service de Dermatologie - Hôpital Larrey; 🇫🇷 Toulouse, France