Mesenchymal Stromal Cells Treatment in Lyell Syndrome: A Pilot Phase 1-2 Open Trial
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Efficacy : Rate of complete or almost complete reepithelialisation
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Adipose derived stromal cells intravenously injected
干预措施: Adipose derived stromal cells intravenously injected (Drug)
结局指标
主要结局
Efficacy : Rate of complete or almost complete reepithelialisation
时间窗: Day 7 after infusion
Safety : Observation of at least one adverse effect
时间窗: Day 10
次要结局
- 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)