The Influence of Extracorporeal Photopheresis on Skin Sclerosis - an Exploratory Clinical Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Modified Rodnan Skin score
研究概览
简要总结
Extracorporeal photopheresis (ECP), also known as extracorporeal photoimmunotherapy or photochemotherapy, is a leukapheresis-based therapy that has been in clinical use for over three decades after receiving FDA approval in 1988. Extracorporeal photopheresis was initially used for the treatment of T-cell lymphoma. Since its introduction, indications for initiating ECP were continuously extended to the treatment of Graft-versus-Host Disease (GvHD), systemic sclerosis, and in the field of solid organ transplantation. There is also evidence supporting the use of ECP in generalized morphea, a form of scleroderma limited to the skin, and in eosinophilic fasciitis, which is a rare, localized fibrosing disorder of the fascia.
Concluding the results of the published studies, there is evidence that ECP has a positive effect on fibrosing disorders of the skin. Furthermore, in clinical practice, it has been observed that patients with systemic sclerosis, who undergo ECP treatment, show improvement of the skin lesions or a deceleration in the formation progress of such lesions during the therapy. Same findings can be observed in patients with sclerotic skin lesions of the skin, for example in the context of a GvHD.
There are no clinical studies so far that describe these processes using objective measuring methods. Furthermore, the mechanism of action of ECP in systemic sclerosis and other fibrosing disorders with skin manifestations, has not yet been conclusively clarified. Serological markers for monitoring the progress of the therapy and determining the prognosis are also missing. Thus, a consensus regarding the frequency and duration of ECP for the therapy of systemic scleroderma or sclerotic diseases has not yet been reached.
This study aims at evaluating the influence of Extracorporeal Photopheresis on the quality and functionality of sclerotic skin lesions assessed by several objective methods. Furthermore, potential biomarkers, which are being investigated in current studies, are to be determined in order to evaluate the influence of ECP on those biomarkers and better understand the mechanism of action of ECP on systemic sclerosis and fibrosing disorders involving the skin.
详细描述
Background and Rationale:
Extracorporeal photopheresis:
In this immunomodulatory therapy, the apheresis leukocytes of the patients are irradiated with ultraviolet (UV) A in the presence of a photosensitizing agent, 8-methoxypsoralen prior to reinfusion to the patient. The mechanism of action of ECP has not yet been conclusively clarified. However, it has been shown that ECP modulates dendritic cells, modifies the cytokine profile and stimulates several T cell subpopulations, in particular regulatory T cells (Treg). The accumulated experience shows ECP to be well tolerated, with no clinically significant side effects and no long-term complications. Extracorporeal photopheresis is available as first-line as well as second-line therapy and can be combined with systemic drug therapies.
Scleroderma and ECP:
Scleroderma comprises a spectrum of autoimmune fibrosing disorders characterized by vascular alterations, fibrosis, and subsequent atrophy of the skin, subcutaneous tissue and muscles. Depending on the form of the disease, internal organs may also be affected in various degrees (e.g. alimentary tract, lungs, heart, kidney, central nervous system). It is usually classified into systemic sclerosis (generalized scleroderma) and morphea (localized scleroderma), distinguished by visceral involvement in the generalized form and disease limited to the skin and subcutaneous tissue in the localized form. Prognosis depends mainly on renal, cardiac and pulmonary manifestations.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Systemic sclerosis, morphea, sclerodermiform GvHD or eosinophilic fasciitis, with duration less than 5 years.
- •Ability and willingness to both understand and carry out the study requirements
排除标准
- •Participation in another study, currently or in the previous four weeks.
结局指标
主要结局
Modified Rodnan Skin score
时间窗: Week 24 ± 2
The skin thickening is being assessed by palpation of the skin in 17 areas of the body using a 0-3 scale, where 0 = normal, 1 = mild thickness, 2 = moderate thickness and 3 = severe thickness (total score=51).
次要结局
- Change in percentage counts of Th1, Th2, Th17 and Treg cells after ECP cycle.(Week 24 ± 2)
- Transepidermal water loss (TEWL) at control skin area(Week 12 ± 2)
- Stratum corneum hydration (SCH) at control skin area(Week 12 ± 2)
- Skin surface sebum level at lesional skin area(Week 24 ± 2)
- Serum levels of CXCL4.(Week 24 ± 2)
- Acute change in serum levels of CXCL4.(Week 24 ± 2)
- Skin thickness at lesional skin area(Week 24 ± 2)
- Serum levels of proinflammatory factors Interleukin 4 (IL-4), Interleukin 9 (IL-9), Interleukin 33 (IL-33) and Transforming growth factor beta (TGF-beta).(Week 8 ± 2)
- Serum levels of Platelet factor 4 (CXCL4).(Week 8 ± 2)
- Skin thickness at control skin area(Week 24 ± 2)
- Skin firmness at control skin area(Week 24 ± 2)
- Acute change in serum levels of proinflammatory factors IL-4, IL-9, IL-33 and TGF-beta.(Week 24 ± 2)
- Percentage counts of T helper type 1 (Th1), T helper type 2 (Th2), T helper type 17 (Th17) and Treg cells.(Week 8 ± 2)
- TEWL at lesional skin area(Week 24 ± 2)
- TEWL at control skin area(Week 24 ± 2)
- SCH at lesional skin area(Week 24 ± 2)
- SCH at control skin area(Week 24 ± 2)
- Skin firmness at lesional skin area(Week 24 ± 2)
- Skin surface sebum level at control skin area(Week 24 ± 2)
- Acute change in serum levels of Platelet factor 4 (CXCL4).(Week 8 ± 2)
- Change in serum levels of proinflammatory factors IL-4, IL-9, IL-33 and TGF-beta after ECP cycle.(Week 24 ± 2)
- Serum levels of proinflammatory factors IL-4, IL-9, IL-33 and TGF-beta.(Week 24 ± 2)
- Change in serum levels of proinflammatory factors IL-4, IL-9, IL-33 and TGF-beta after ECP cycle(Week 16 ± 2)
- Change in serum levels of CXCL after ECP cycle.(Week 24 ± 2)
- Acute change in percentage counts of Th1, Th2, Th17 and Treg cells(Week 8 ± 2)
- Percentage counts of Th1, Th2, Th17 and Treg cells.(Week 24 ± 2)
- Change in serum levels of CXCL4 after ECP cycle.(Week 16 ± 2)
- Acute change in percentage counts of Th1, Th2, Th17 and Treg cells.(Week 24 ± 2)
研究者
Ulrike Blume-Peytavi, MD
Prof. Dr. Ulrike Blume-Peytavi
Charite University, Berlin, Germany