Replicative Stress in Hair Follicle Stem Cells and Pathogeny of Hidradenitis Suppurativa

NCT05531747 | Recruiting

• 1 other identifier: APHP211351
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Hidradenitis Suppurativa is a recurrent chronic inflammatory follicular occlusive disease affecting hair follicles. HS is notoriously difficult and challenging to treat with a high morbidity impact and could be classified as an unmet medical need with no efficient therapeutic options. Objective: Investigators previously showed that Outer Root Sheath Cells (ORS) isolated from hair follicle of HS patients (HS-ORS) have a pro-inflammatory phenotype and secrete spontaneously IP-10 and RANTES. To identify the mechanisms involved in the pro-inflammatory phenotype of HS-ORS, investigators performed a transcriptomic analysis in healthy and HS patients. This revealed: (i) an IFN signature, (i) a dysregulation of genes involved in cell proliferation and differentiation, and (iii) an upregulation of DNA damage response and cell cycle G2/M checkpoint pathways in HS-ORS. These findings support the notion that, in HS patients, a perturbation of HF-SC homeostasis leading to an increased proliferation induces a replicative stress and an accumulation of cytoplasmic ssDNA, stimulating IFN synthesis through IFI16-STING pathway. Interestingly, replicative stress in ORS were present in some but not all patients with Hidradenitis Suppurativa. The goal of study is to determine replicative stress in ORS in a large cohort of HS patients. Method Patients will be enrolled in the Mondor Dermatology department, during routine care. A dermatologist will check all inclusion and exclusion criteria with the technical support of a research technician of the Henri Mondor Clinical Investigation Center. Medical history, clinical data, comorbidities and concomitant therapies will be prospectively recorded in a dedicated case report form. Skin biopsies will be performed in perilesional zone rich in hair follicles. mRNA will be extracted from freshly isolated hair follicle cells and some slides will be prepared and stored at -80°C to perform immunohistochemistry analysis on freshly isolated hair follicle cells. PBMC and serum will be collected. All these biological samples will allow us to quantify the replicative stress in HS-ORS of each patient, and to quantify several cytokine of interest : IFN de type 1, IL-17, IL-6, TNF-α, IL-10 This study will allow investigators to evaluate the rate of patients with replicative stress in hair follicle stem cells in Hidradenitis Suppurativa. The investigator will also determine whether HF-SC replication stress correlates with clinical characteristics and/or with clinical course and/or comorbidities.

Conditions

Hidradenitis Suppurativa

Keywords

cytokine; inflammation; replicative stress; Hidradenitis Suppurativa

Outcome Measures

Primary Outcomes (1)

• Replicative stress in hair follicle stem cells in Hidradenitis Suppurativa

  Evaluation of the rate of patients with replicative stress in hair follicle stem cells in Hidradenitis Suppurativa

  The primary outcome will be evaluated at baseline

Study Arms (1)

Physiopathologic exploration

EXPERIMENTAL

A non randomised study with one arm, addind experimental acts to standard of care (skin biopsy and biological sample ) in order to explore Hidradenitis Suppurativa physiopathology

Other: Skin biopsy; Other: Blood sample

Interventions

Skin biopsy OTHER

A maximum of 2 superficial skin biopsies (epidermis/dermis), allowing 10 hair follicles to be obtained, at the edge of the affected area, in healthy territory (excluding the face and folds but not excluding the pubic region), at initiation visit.

Physiopathologic exploration

Blood sample OTHER

42mL of blood (6 tubes of 7mL) sampled at initiation visit

Physiopathologic exploration

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients referred to the consultation of dermatology of Henri Mondor Hospital
• Diagnosis of Hidradenitis Suppurativa
• Age\> 18 y.o.
• Affiliation to a social security system

You may not qualify if:

• Patient under tutorship or curatorship
• Breastfeeding or pregnant women
• Refusal to sign the consent letter
• Patients benefiting from State Medical Aid

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Assistance Publique Hôpitaux de Paris - CHU Henri Mondor

Créteil, Val-de-marne, 94010, France

RECRUITING

MeSH Terms

Conditions

Hidradenitis Suppurativa; Inflammation

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Skin Diseases, Bacterial; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Skin Diseases, Infectious; Suppuration; Skin Diseases; Skin and Connective Tissue Diseases; Hidradenitis; Sweat Gland Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Claire HOTZ, MD

CONTACT

33-1-49-81-37-96; claire.hotz@aphp.fr

Philippe Le Corvoisier, MD PhD

CONTACT

33-1-49-81-37-96; philippe.lecorvoisier@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: Biological assays will be performed by technician blinded from patients clinical status
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2022
• First Posted: September 8, 2022
• Study Start: June 13, 2022
• Primary Completion (Estimated): June 13, 2029
• Study Completion (Estimated): December 13, 2029
• Last Updated: February 6, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)