Adipose Derived Stromal Cells, Epidermal Necrolysis, Lyell Syndrome, Mesenchymal Stromal Cells, Overlap Syndrome, Toxic Epidermal Necrolysis
Conditions
Keywords
Epidermal necrolysis, Lyell syndrome, toxic epidermal necrolysis, Overlap syndrome, Mesenchymal stromal cells, Adipose derived stromal cells
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.
Interventions
DRUGAdipose derived stromal cells intravenously injected
2×10\^6/kg of Adipose derived stromal cells A single injection at D0 (performed maximum three days post-admission).
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients ≥ 18 and ≤ 75 years-old * Admission ≤ 10 days after the index date (date of the first symptoms of the disease) * 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) * Who, after the nature of the study has been explained to them or a support person (if applicable), and prior to any protocol specific procedures being performed, have given written consent according to local regulatory requirements * 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 * Detection of Coronavirus SARS CoV-2 RNA on admission (positive RT-PCR), if performed in the usual care * 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety : Observation of at least one adverse effect | Day 10 |
| Efficacy : Rate of complete or almost complete reepithelialisation | Day 7 after infusion |
Secondary
| Measure | Time frame |
|---|---|
| Duration of hospitalisation according to our historical cohort related to onset of the disease | Month 12 |
| Duration of hospitalisation according to our historical cohort related to SCORTEN | Month 12 |
| Duration of each mucous membranes healing ie.(buccal, nasal, genital, eyes) | at Month 12 |
| Rate of sepsis | at Month 12 |
| Rate of intensive care transfer | at Month 12 |
| Rate of observed and predicted death by the SCORTEN | at one month |
| Th1/Th2 immune response in the peripheral blood of the patients | after injection at Day 0, Day 10, Month 1 |
| 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 |
| 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 |
| Rate of sequelae | at Month 12 |
| Duration of hospitalisation according to our historical cohort related to BSA involved | Month 12 |
Countries
France
Contacts
Primary ContactSaskia Oro, MD
Backup ContactCharline Menanteau, MSc
Outcome results
None listed