Pleiotropic Role of TRPV1 in Psoriasis Inflammation

NCT04848194 | Completed

• 1 other identifier: 29BRC21.0013
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Widely expressed in the sensory nerve endings of the skin, Transient Receptor Potential Vanilloid 1 (TRPV1) is a receptor that plays an important role in the perception of pain and pruritus but also in skin inflammation, primarily by inducing the local release of several neuropeptides. Although the mechanisms by which TRPV1-sensitizing inflammatory mediators in damaged skin have received considerable attention, the role of TRPV1 in psoriasis has so far been little explored. However, two studies have reported that ablation of sensory nerves expressing TRPV1 reduced psoriasiform skin inflammation, demonstrating the neuronal contribution to inflammation in psoriasis. However, the expression of TRPV1 is not limited to neurons alone. TRPV1 is also expressed by epidermal keratinocytes and skin microvessels. For example, in 2018, transcriptomic analysis of psoriatic patient skins (by definition devoid of neuron nuclei) revealed that TRPV1 expression was increased in the skin of psoriatic patients suffering from itching (pruritus). Regarding human keratinocytes, it is recognized that the activation of TRPV1 present on their surface induces the release of pro-inflammatory factors such as cyclooxygenase-2. In addition, the investigators have demonstrated that TRPV1 has a pivotal role in the keratinocyte production of inflammatory mediators, which is mediated by the protease-activated receptor-2 (PAR-2). However, the role of vascular TRPV1 in inflammation is not described. The investigators hypothesize that in addition to neuronal TRPV1, non-neuronal TRPV1 receptors of non-neuronal cells (keratinocytes and endothelial cells) may be involved in the vicious circle of the inflammatory process characteristic of psoriasis. Putting TRPV1 at the center of the deregulation of the homeostatic balance including epithelial, neuronal and vascular inflammation in psoriasis is totally innovative.

Conditions

Inflammation; Skin; Psoriasis

Keywords

psoriasis; TRVP1

Outcome Measures

Primary Outcomes (1)

• Role of TRPV1 receptors expressed by sensory neurons and non-neuronal cells (keratinocytes and endothelial cells) in the inflammatory process characteristic of psoriasis.

  Density of intra-epidermal nerve fibers expressing the TRPV1 receptor

  1 day

Secondary Outcomes (5)

• Density changes of intra-epidermal nerve fibers expressing neuropeptides

  1 day

• Changes in endothelial cell density between an injured and an uninjured area of the same patient

  1 day

• Changes in endothelial cell density between an injured and an uninjured area of the same patient

  1 day

• Changes in endothelial cell density between an injured and an uninjured area of the same patient

  1 day

• Changes in the density of keratinocytes and their contacts with nerve fibers

  1 day

Study Arms (1)

All patients

OTHER

All patients with psoriasis recruted by dermatological departement.

Procedure: skin biopsy and blood sampling

Interventions

skin biopsy and blood sampling PROCEDURE

* 4 skin biopsies outside the face under local anesthesia: 2 in damaged zone, 2 in non-damage zone. * A blood sample

All patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients over 18 years old with psoriasis, with or without itching (pruritus).
• Presence of lesional and non lesional zones, in unexposed areas and surface area (outside the face and folds) large enough to allow the biopsies to be performed
• Patients who have given written consent

You may not qualify if:

• Patients with physical or psychological incapacity to sign consent
• Patients not covered by the Social Security system
• Patients with topical treatments for psoriasis,
• Patients with systemic treatments for psoriasis,
• Patients allergic to lidocaine
• Patients over the age of majority who are subject to legal protection or who are unable to give consent
• Patients deprived of liberty by a judicial or administrative decision
• Pregnant women, parturients and breastfeeding mothers

Sponsors & Collaborators

• University Hospital, Brest: lead

Study Sites (1)

TALAGAS

Brest, 29200, France

Location

MeSH Terms

Conditions

Dermatitis; Psoriasis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Papulosquamous

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2021
• First Posted: April 19, 2021
• Study Start: December 22, 2021
• Primary Completion: January 24, 2024
• Study Completion: January 24, 2024
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available beginning three years and ending fifteen years following the final study report completion
• Access Criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement.

Locations

FR (1)