Effect of IL-2 in Refractory Autoimmune Encephalitis Patients: A Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 主要终点
- Change of modified Rankin scale
研究概览
简要总结
The purpose of this study is to determine whether low-dose IL-2 is effective in refractory autoimmune encephalitis.
详细描述
Autoimmune encephalitis is a recently recognized etiology of encephalitis which is mediated by various autoantibodies targeting neural cells or synapses. The responses to immunotherapy is generally good, considerable proportion of patients with autoimmune encephalitis have unfavorable clinical outcomes. Recently, depletion of regulatory T cell (Treg cell) is reported in variable autoimmune diseases and multiple studies have shown that low-dose interleukin-2(IL-2) specifically activates Treg cells to control autoimmunity and inflammation.
Protocol: This study is a single arm open-label study assessing clinical responses to the administration of low-dose IL-2 in autoimmune encephalitis patients who are refractory to first- and second-line immunotherapy.
Objective
To assess the efficacy of low-dose IL-2 in autoimmune encephalitis, resistant to first- and second- line immunotherapy.
Methods: This is a single arm open-label study. Each patients will receive four cycles of subcutaneous Proleukin (Interleukin-2, IL-2) (Week-1; 1.5 million IU (MIU)/d from Day-1 to Day-5, Week-3, -6, -9; 3MIU/d from Day-1 to Day-5) in the hospital. The patients will be followed up for 3 months (Week-21).
Primary outcome - clinical efficacy by modified Rankin Scale Secondary outcome - Immunologic follow-up of Treg cells before, during, and after IL-2 therapy, quality of life, cognitive function, side effect of low-dose IL-2
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
- 19 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years
- •Clinical diagnosis of autoimmune encephalitis
- •Positive for autoantibody (serum and or CSF) : NMDAR, anti-leucine-rich glioma inactivated-1(LGI-1), contactin-associated protein-like 2 (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) 1, AMPA2, GABAB-R, anti-Hu, -Yo, -Ri, -Ma2, -CV2/collapsing response mediator protein 5 (CRMP5), -amphiphysin, or glutamic acid decarboxylase (GAD)
- •Refractory to first-line (high-dose steroid or intravenous immunoglobulin) and second line (rituximab or cyclophosphamide) immunotherapy
- •Written informed consent form.
排除标准
- •low hemoglobin <8.0 g/dL, absolute neutrophil count<1600/mm3, lymphocytes <600/mm3, platelets <140,000/mm3
- •heart failure (≥ grade III NYHA), hepatic insufficiency (aspartate amino transferase >200 IU/L, amino alanine transferase, >200 IU/L), or lung failure
- •Positive for HIV serology, active hepatitis B
- •Significant abnormality in chest X-ray other than these linked to the diseases under investigation
- •Infection
- •Other progressive neurological degenerative disease.
- •Poor venous access not allowing repeated blood tests
- •pregnant or lactating women
研究组 & 干预措施
Proleukin
Proleukin (subcutaneous injection) 1.5 MIU/day from day 1 to 5 at W1 3 MIU/day from day 1 to day 5 at W3, W6, and W9
干预措施: Proleukin (Drug)
结局指标
主要结局
Change of modified Rankin scale
时间窗: Week 0,12
次要结局
- The change of percentage of regulatory T (Treg) cells(Week 1, 3, 5, 9, 12, 21)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(Week 1, 3, 5, 9, 12, 21)
- Beck Depression Inventory (BDI)(Week 21)
- Quality of Life in Epilepsy Inventory (QOLIE)-31(Week 21)
- Cognitive function(Week 21)
研究者
Kon Chu
Clinical Professor
Seoul National University Hospital