LYell SYndrome MEsenchymal Stromal Cells Treatment (LYSYME)
Primary Purpose
Epidermal Necrolysis, Lyell Syndrome, Toxic Epidermal Necrolysis
Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Adipose derived stromal cells intravenously injected
Sponsored by
About this trial
This is an interventional treatment trial for Epidermal Necrolysis focused on measuring Epidermal necrolysis, Lyell syndrome, toxic epidermal necrolysis, Overlap syndrome, Mesenchymal stromal cells, Adipose derived stromal cells
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Adipose derived stromal cells intravenously injected
Arm Description
Outcomes
Primary Outcome Measures
Safety : Observation of at least one adverse effect
Efficacy : Rate of complete or almost complete reepithelialisation
Secondary Outcome Measures
Rate of observed and predicted death by the SCORTEN
Duration of hospitalisation according to our historical cohort related to BSA involved
Duration of hospitalisation according to our historical cohort related to onset of the disease
Duration of hospitalisation according to our historical cohort related to SCORTEN
Duration of each mucous membranes healing ie.(buccal, nasal, genital, eyes)
Rate of sepsis
Rate of intensive care transfer
Rate of sequelae
Th1/Th2 immune response in the peripheral blood of the patients
Evaluation of expression profile of Th1/Th2 associated chemokines and anti-inflammatory chemokines in the peripheral blood
Epidermal chimerism study on healed skin biopsy
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.
Full Information
NCT ID
NCT04711200
First Posted
November 30, 2020
Last Updated
May 2, 2022
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT04711200
Brief Title
LYell SYndrome MEsenchymal Stromal Cells Treatment
Acronym
LYSYME
Official Title
Mesenchymal Stromal Cells Treatment in Lyell Syndrome: A Pilot Phase 1-2 Open Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2022 (Anticipated)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
September 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epidermal Necrolysis, Lyell Syndrome, Toxic Epidermal Necrolysis, Overlap Syndrome, Mesenchymal Stromal Cells, Adipose Derived Stromal Cells
Keywords
Epidermal necrolysis, Lyell syndrome, toxic epidermal necrolysis, Overlap syndrome, Mesenchymal stromal cells, Adipose derived stromal cells
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Adipose derived stromal cells intravenously injected
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Adipose derived stromal cells intravenously injected
Intervention Description
2×10^6/kg of Adipose derived stromal cells A single injection at D0 (performed maximum three days post-admission).
Primary Outcome Measure Information:
Title
Safety : Observation of at least one adverse effect
Time Frame
Day 10
Title
Efficacy : Rate of complete or almost complete reepithelialisation
Time Frame
Day 7 after infusion
Secondary Outcome Measure Information:
Title
Rate of observed and predicted death by the SCORTEN
Time Frame
at one month
Title
Duration of hospitalisation according to our historical cohort related to BSA involved
Time Frame
Month 12
Title
Duration of hospitalisation according to our historical cohort related to onset of the disease
Time Frame
Month 12
Title
Duration of hospitalisation according to our historical cohort related to SCORTEN
Time Frame
Month 12
Title
Duration of each mucous membranes healing ie.(buccal, nasal, genital, eyes)
Time Frame
at Month 12
Title
Rate of sepsis
Time Frame
at Month 12
Title
Rate of intensive care transfer
Time Frame
at Month 12
Title
Rate of sequelae
Time Frame
at Month 12
Title
Th1/Th2 immune response in the peripheral blood of the patients
Time Frame
after injection at Day 0, Day 10, Month 1
Title
Evaluation of expression profile of Th1/Th2 associated chemokines and anti-inflammatory chemokines in the peripheral blood
Time Frame
after injection at Day 0, Day 10, Month 1.
Title
Epidermal chimerism study on healed skin biopsy
Time Frame
at 1 month
Title
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.
Time Frame
at Day 5, Day 10 and Day15
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Saskia Oro, MD
Phone
0149812536
Ext
+33
Email
saskia.oro@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Myriem Carrrier, MSc
Phone
0144841752
Email
myriem.carrier@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Saskia Oro, MD
Organizational Affiliation
saskia.oro@aphp.fr
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
17805350
Citation
Mockenhaupt M, Viboud C, Dunant A, Naldi L, Halevy S, Bouwes Bavinck JN, Sidoroff A, Schneck J, Roujeau JC, Flahault A. Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol. 2008 Jan;128(1):35-44. doi: 10.1038/sj.jid.5701033. Epub 2007 Sep 6.
Results Reference
background
PubMed Identifier
27317286
Citation
Creamer D, Walsh SA, Dziewulski P, Exton LS, Lee HY, Dart JK, Setterfield J, Bunker CB, Ardern-Jones MR, Watson KM, Wong GA, Philippidou M, Vercueil A, Martin RV, Williams G, Shah M, Brown D, Williams P, Mohd Mustapa MF, Smith CH. U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016. Br J Dermatol. 2016 Jun;174(6):1194-227. doi: 10.1111/bjd.14530. No abstract available.
Results Reference
background
PubMed Identifier
21367635
Citation
Roux S, Leotot J, Chevallier N, Bierling P, Rouard H. [Mesenchymal stromal cells: Biological properties and clinical prospects]. Transfus Clin Biol. 2011 Feb;18(1):1-12. doi: 10.1016/j.tracli.2011.01.001. Epub 2011 Mar 1. French.
Results Reference
background
PubMed Identifier
19780713
Citation
Chung HM, Won CH, Sung JH. Responses of adipose-derived stem cells during hypoxia: enhanced skin-regenerative potential. Expert Opin Biol Ther. 2009 Dec;9(12):1499-508. doi: 10.1517/14712590903307362.
Results Reference
background
PubMed Identifier
28476287
Citation
Duong TA, Valeyrie-Allanore L, Wolkenstein P, Chosidow O. Severe cutaneous adverse reactions to drugs. Lancet. 2017 Oct 28;390(10106):1996-2011. doi: 10.1016/S0140-6736(16)30378-6. Epub 2017 May 2. Erratum In: Lancet. 2017 Oct 28;390(10106):1948.
Results Reference
result
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LYell SYndrome MEsenchymal Stromal Cells Treatment
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