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

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.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Biological: Skin biopsies; Biological: Blood sample

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31400
    • Service de Dermatologie - Hôpital Larrey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 : 20 subjects with plaque psoriasis; Intervention: skin biopsies and blood sample	Biological: Skin biopsies; 3 biopsies on lesion skin (and one more for the first fifteen subjects in group 1); Biological: Blood sample; One blood sample for the group 1 only.
Experimental: Group 2 : 10 subjects with atopic dermatitis; Intervention: skin biopsies	Biological: Skin biopsies; 3 biopsies on lesion skin (and one more for the first fifteen subjects in group 1)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression of Cav1.4 calcium channels in Th17 lymphocytes	Immunohistochemistry (IHC) and in situ hybridation (HIS)	Baseline

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Pierre Fabre Dermo Cosmetique
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; Centre National de la Recherche Scientifique, France
• Investigators: Principal Investigator: Paul CARL, Pr., Service de Dermatologie - Hôpital Larrey

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2016
• Primary Completion (Actual): November 13, 2017
• Study Completion (Actual): November 13, 2017

Study Registration Dates

• First Submitted: July 1, 2020
• First Submitted That Met QC Criteria: July 6, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Actual): July 14, 2020
• Last Update Submitted That Met QC Criteria: July 10, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Th17; Lymphocyte; Cav1.4; Channel
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: CaPSO17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No