LYell SYndrome MEsenchymal Stromal Cells Treatment

Phase 1

Not yet recruiting

• Conditions: Epidermal Necrolysis; Mesenchymal Stromal Cells; Toxic Epidermal Necrolysis; Overlap Syndrome; Lyell Syndrome; Adipose Derived Stromal Cells
• Interventions: Drug: Adipose derived stromal cells intravenously injected

• Registration Number: NCT04711200
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions (SCARs) to drugs.

To date, no curative drug has demonstrated with a good level of evidence its ability to promote SJS and TEN healing and could contribute to earlier reepithelialisation. Mesenchymal stroma cells (MSCs) therapy represents a new therapeutic approach. eg, in patients with cardiovascular diseases, neurological diseases, renal transplantation, lung diseases as acute respiratory distress syndrome.

Recently, MSCs have been proposed in both burn wound healing with a significantly decrease of the unhealed burn area and in cutaneous radiation.

Moreover, MSCs have immunomodulation properties potentially effective in refractory acute and chronic graft versus host disease (GVHD) by improving thymic function and induction of Tregs. Indeed, MSCs are able to migrate to inflamed tissues after stimulation by pro-inflammatory cytokines and to modulate the local inflammatory reactions. MSCs have also demonstrated their ability to promote tissue remodelling, angiogenesis and immunomodulation through either differentiation or secretion of several growth factors such as VEGF, basic FGF and various cytokines.

Therefore, combining their immunomodulation effect and secretion of soluble factors involved in wound repair, MSCs might be valuable as a cell therapy strategy for promoting cutaneous healing in SJS-TEN syndrome and subsequently decrease the morbi-mortality.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-11-30
• Study First Submitted QC: 2021-01-12
• Study First Posted: 2021-01-15
• Status Verified: 2022-04
• Last Update Submitted: 2022-05-02
• Last Update Posted: 2022-05-03
• Study Start: 2022-09
• Primary Completion: 2025-09
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Patients aged from 18 to 75 years-old
• Admission less than 10 days after onset of the reaction
• Patient with confirmed SJS-TEN diagnosis hospitalized in the department of Dermatology or intensive care medicine
• At least 10 % of detachable-detached body surface area at any time during the first 10 days after the index date (date of the first symptoms of the disease)
• Written consent from patient or trustworthy person or legal representant or family member
• Affiliated to a social security scheme

Exclusion Criteria

• Pregnant or breastfeeding women
• History of malignant disease within the past ten years and or presence of metastasis
• Positive serology for HIV
• Active infection for hepatitis B or C
• Decompensated cardiac failure
• Uncontrolled epilepsia
• Previous history of allogenic bone marrow transplantation
• Participation in other interventional drug research
• Patient deprived of liberty by a judicial or administrative decision or under the protection of justice
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the research protocol and follow-up schedule
• Patient under tutorship or curatorship
• Patient under psychiatric care according to art. L1121-6 CSP

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Adipose derived stromal cells intravenously injected	Adipose derived stromal cells intravenously injected	-

Primary Outcome Measures

Name	Time	Method
Efficacy : Rate of complete or almost complete reepithelialisation	Day 7 after infusion
Safety : Observation of at least one adverse effect	Day 10

Secondary Outcome Measures

Name	Time	Method
Rate of observed and predicted death by the SCORTEN	at one month
Duration of hospitalisation according to our historical cohort related to SCORTEN	Month 12
Duration of hospitalisation according to our historical cohort related to BSA involved	Month 12
Duration of hospitalisation according to our historical cohort related to onset of the disease	Month 12
Rate of sepsis	at Month 12
Duration of each mucous membranes healing ie.(buccal, nasal, genital, eyes)	at Month 12
Rate of intensive care transfer	at Month 12
Rate of sequelae	at Month 12
Evaluation of expression profile of Th1/Th2 associated chemokines and anti-inflammatory chemokines in the peripheral blood	after injection at Day 0, Day 10, Month 1.
Epidermal chimerism study on healed skin biopsy	at 1 month
Th1/Th2 immune response in the peripheral blood of the patients	after injection at Day 0, Day 10, Month 1
Cutaneous re-epithelialization rate at D5, D10 and D15 post-infusion according to the percentage of cutaneous BSA re-epithelialized in comparison to maximal cutaneous detachable-detached BSA observed.	at Day 5, Day 10 and Day15