Efficacy of Tacrolimus and i.v.-Immunoglobulins in Rasmussen Encephalitis With Start of Treatment in the Acute Disease Stage. Prospective, Randomised, Open Parallel Group Study
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Time to exit, criteria: Deterioration of motor function of the affected side by 15 % (>11 yrs of age: 8%) measured by the "Motricity Index" (scale 0-100) or deterioration of the "Hemispheric ratio" assessed by regular MRI scans by 15% (>11 yrs: 8%).
研究概览
简要总结
Rasmussen encephalitis (RE) is a rare but severe chronic inflammatory brain disease of unknown origin affecting one brain hemisphere. It is usually accompanied by intractable epilepsy. In addition, it often leads to severe disability due to functional deficits caused by atrophy of one brain hemisphere. Hemispherectomy is an effective means of surgical treatment of the epilepsy. It renders the patient, however, hemiplegic, hemianopic and (if the language dominant hemisphere is affected) aphasic. To slow down or even stop the progressive inflammatory damage to the affected brain hemisphere, immunotherapies may be beneficial. According to a literature survey, tacrolimus (twice daily intake of capsules) and intravenous immunoglobulins (monthly infusions) are the most promising compounds for this. In the investigators' study, these two types of treatment are randomly assigned to patients with disease onset within the last year and not too far advanced disability or hemispheric brain injury. The patients are followed to assess prospectively the functional and brain MRI course of the disease.
详细描述
- Trial design/2. Trial interventions Patients are screened in epileptological, neuropediatric, and neurological centers all over Germany. The study design was approved on a meeting in Bonn on April 20, 2002 by several external participants and by the ethical committee of the University of Bonn. Patients with the suspected diagnosis of RE are transferred to the Department of Epileptology of the University of Bonn. If the diagnosis "RE in the acute stage" is confirmed and the patient or (in children) the parents give informed consent, the patients are randomized to one of the two active treatment arms.
The study was started on 1.10.2002. The first patient was included on 20.11.2002.
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Inclusion/exclusion criteria See appropriate section
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Duration Recruitment started on 1.10.2002 and will go on until the proposed number of study participants has been included. A patient remains in the study until he or she reaches one of the predefined exit parameters (see below, #4.5). Every patient will be followed under study conditions for at least 12 months (to obtain true long term results).
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Outcome measures See appropriate section.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients meeting at least two of the following three criteria:
- •Clinical: Epilepsia partialis continua or progressive* hemiparesis
- •MRI: Progressive* cerebral hemiatrophy
- •Histopathology: T cell dominated encephalitis with activated microglial cells (typically, but not necessarily forming nodules) and reactive astrogliosis. Numerous macrophages, B cells or plasma cells or positive signs of viral infections (viral inclusion bodies or immunohistochemical demonstration of viral protein) exclude the diagnosis of RE.
- •"Progressive" means that at least two sequential clinical examinations or MRI studies documenting increasing deficits or tissue loss are required to meet the respective criteria.
排除标准
- •Neuroradiological signs of a bihemispheric encephalitis.
- •Wave-like course with history of repeated remissions.
- •Infectious disease as a contraindication to an immunosuppressive therapy.
- •Paraneoplastic encephalitis.
- •Previous treatment with > 3 weeks of corticosteroids or tacrolimus or > 1,2 g/kg IVIG or > 5 PEX/PAI within the last three months.
- •Onset of acute disease stage more than 12 months ago.
- •Patient already in residual stage, i.e., stable neurological deficit since >6 months.
- •Hemispheric Ratio < 80% (< 90% in patients > 11 years)
- •Histopathological evidence of cerebral inclusion bodies indicating a viral infection
研究组 & 干预措施
Group 1
Tacrolimus capsules ("Prograf"; dosing according to blood trough levels: 12-15 ng/ml during months 1-6, 5-10 ng/ml during months 7-12 and 5-8 ng/ml thereafter)
干预措施: Tacrolimus (Drug)
Group 2
Intravenous immunoglobulins (IVIG) infusions ("Octagam"; dosing: initially on three consecutive days 0,4 g/kg KG, thereafter 0,4 g/kg KG every month, after 12 months of treatment every two months).
干预措施: i.v. immunoglobulins (Drug)
结局指标
主要结局
Time to exit, criteria: Deterioration of motor function of the affected side by 15 % (>11 yrs of age: 8%) measured by the "Motricity Index" (scale 0-100) or deterioration of the "Hemispheric ratio" assessed by regular MRI scans by 15% (>11 yrs: 8%).
时间窗: until final included subject has been followed for one yer
次要结局
- seizure frequency, "Burden of disease" scale, neuropsychological performance, quality of life, T cell receptor studies (H Wiendl, Würzburg)(until final included subject has been followed for one yer)