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

Hidradenitis Suppurativa Clinical Trial

— Fol-Hydra  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05531747
• Other study ID #: APHP211351
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 30, 2022
• Est. completion date: March 30, 2024

Study information

• Verified date: June 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Claire HOTZ, MD
• Phone: 33-1-49-81-37-96
• Email: claire.hotz[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: March 30, 2024
• Est. primary completion date: March 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Patient under tutorship or curatorship

• Breastfeeding or pregnant women

• Refusal to sign the consent letter

• Patients benefiting from State Medical Aid

Related Conditions & MeSH terms

• Hidradenitis
• Hidradenitis Suppurativa

Intervention

Other:
• Skin biopsy
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.
• Blood sample
42mL of blood (6 tubes of 7mL) sampled at initiation visit

Locations

Country	Name	City	State
France	Assistance Publique Hôpitaux de Paris - CHU Henri Mondor	Créteil	Val-de-marne

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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