The Effectiveness of ECP in Diffuse Cutaneous Systemic Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Change in skin thickness measured by modified Rodnan Skin Score
研究概览
简要总结
The purpose of this study is to assess feasibility, safety and preliminary efficacy of Extracorporeal Photopheresis in the treatment of active diffuse cutaneous systemic sclerosis (dcSSc). This pilot study will help to determine if further study (a RCT) is justified.
详细描述
Systemic sclerosis (SSc, Scleroderma) is a multisystem autoimmune disease characterized by widespread vascular injury and progressive fibrosis of the skin and internal organs. There is no effective treatment for the majority of patients with diffuse scleroderma (diffuse cutaneous systemic sclerosis; dcSSc). Only few therapies have shown modest benefits in regard to some specific organ pathologies. In the early stage of dcSSc, it may be possible to reverse inflammation and reduce the probability of irreversible fibrosis via significant immune modulation as later, often the fibrosis doesn't improve with treatment.
This is a pilot study that will treat 15 participants with dcSSc who meet the eligibility criteria. The objective of the study is to determine if the benefit of Extracorporeal photopheresis (ECP) and safety are favorable in order to consider and help in the design of a randomized controlled trial (RCT). This is a Phase II study that is uncontrolled and patients will remain on their background immunosuppressive treatment unless if contraindicated for safety or drug interactions. The trial is powered to show a mean change in skin thickness measured with modified Rodnan skin score (mRSS) of ≥5 over one year, in an uncontrolled, unblinded study. The Health Assessment Questionnaire Disability Index (HAQ-DI), patient and physician global scores, inflammatory markers, and combined response index in SSc (CRISS) will all be exploratory outcomes. Other outcomes such as changes in cells on skin biopsies from baseline to end of the trial will be explored if the study is positive.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with SSc, aged 18 years or older, and:
- •Subjects must meet the ACR/EULAR classification criteria for SSc (2013).
- •Early dcSSc (within 5 years of first non-Raynaud's phenomenon symptom) or any other dcSSc patients who have at least one of the signs of disease activity: mRSS of 15 or more, presence of tendon friction rubs, elevated inflammatory markers thought to be due to active dcSSc and not related to other issues such as infection or ILD with FVC% predicted <80% or HRCT showing ILD thought to be from SSc.
- •Able to give informed consent.
排除标准
- •Poor pulmonary function (FVC<40% and/or DLCO<30%).
- •Class IV PAH or PH.
- •Clinically significant cardiac disease.
- •Significant concurrent, uncontrolled medical condition including, but not limited to, renal, cardiac, hepatic, pancreatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease; and cancer (i.e. co-existing melanoma, basal cell, or squamous cell skin carcinoma).
- •Chronic or ongoing active infectious disease requiring systemic treatment, including active tuberculosis (TB) infection.
- •Seropositivity for human immunodeficiency virus (HIV) at study entry.
- •Active viral infection with viral replication of hepatitis B or C virus at study entry.
- •Thrombophilia.
- •Contraindications to heparin including history of heparin-induced thrombocytopenia (HIT) or heparin-induced thrombocytopenia and thrombosis (HITTS), history of thrombocytopenia with pentosan polysulfate, known hypersensitivity to heparin or pork products.
- •Low Platelet count (less than 100,000 per mm3).
- •Aphakia (absence or loss of the eye's lens and has not been replaced with an artificial lens), because of the significantly increased risk of retinal damage due to the absence of lenses.
- •Severe anemia (hemoglobin <70g/L).
- •High white blood cell count (greater than 25000 mm3).
- •A history of surgical spleen removal.
- •A history of a light sensitive disease state, i.e. lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum and albinism.
- •Previous idiosyncratic reactions to psoralen compounds.
- •Patients who are using photosensitizing drugs such as anthralin, coal tar or coal tar derivatives, griseofulvin, phenothiazines, nalidixic acid, halogenated salicylanilides (bacteriostatic soaps), sulfonamides, tetracyclines, thiazides, and certain organic staining dyes such as methylene blue, toluidine blue, rose bengal and methyl orange.
- •Treatment with more than 2 immunosuppressants (including mofetil mycophenolate, methotrexate, cyclophosphamide, biologics) at study entry.
- •Pregnancy, breast feeding or child bearing potential without practicing highly effective contraception (and partners for men in the study).
- •Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder).
- •Participation in another clinical trial within six weeks before randomization in this study.
- •Previous use of Extracorporeal photopheresis.
研究组 & 干预措施
Administration of Extracorporeal Photopheresis Treatment
Duration of treatment: 48 weeks. Treatments occur on 2 consecutive days every 4 weeks.
Dose of UVADEX: Treatment Volume x 0.017 = mL of UVADEX for each treatment Treatment Volume (TV) is defined as: The total volume of Buffy Coat plus prime solution that will undergo photoactivation.
Route of administration: Extracorporeal
干预措施: Extracorporeal Photopheresis (ECP) (Device)
Administration of Extracorporeal Photopheresis Treatment
Duration of treatment: 48 weeks. Treatments occur on 2 consecutive days every 4 weeks.
Dose of UVADEX: Treatment Volume x 0.017 = mL of UVADEX for each treatment Treatment Volume (TV) is defined as: The total volume of Buffy Coat plus prime solution that will undergo photoactivation.
Route of administration: Extracorporeal
干预措施: UVADEX (Drug)
结局指标
主要结局
Change in skin thickness measured by modified Rodnan Skin Score
时间窗: 48 weeks
modified Rodnan Skin Score (mRSS): is a standard outcome measure for skin disease in SSc and calculated by measuring skin thickness in 17 different body sites (each site scored 0-3, with a total possible additive score of 51). A higher skin score (or a higher "skin thickness") and progression of this score, is predictive of internal organ involvement and mortality. While a lower or improving (lessening) score is associated with favorable outcomes, including better survival.
次要结局
- Change in the diffusing capacity for carbon monoxide(6 and 12 months)
- Combined Response Index in diffuse cutaneous systemic sclerosis score(24 weeks)
- Change in physician global assessment of disease activity(12, 24, 36 and 48 weeks)
- Change in physician global assessment of disease severity(12, 24, 36 and 48 weeks)
- Change in physician global assessment of disease damage(12, 24, 36 and 48 weeks)
- Change in Forced Vital Capacity(6 and 12 months)
- Change in serum concentrations C-Reactive Protein(12, 24, 36 and 48 weeks)
- Change in serum concentrations of Erythrocyte Sedimentation Rate(12, 24, 36 and 48 weeks)
- Change in the modified Rodnan Skin Score(12, 24 and 36 weeks)
- Change in patient global assessment of health status(12, 24, 36 and 48 weeks)
- Change in Scleroderma Health Assessment Questionnaire(12, 24, 36 and 48 weeks)
研究者
Janet Pope
Head of Rheumatology
London Health Sciences Centre OR Lawson Research Institute of St. Joseph's