Efficacy of Tacrolimus and I.V.-Immunoglobulins in Rasmussen Encephalitis
Recruitment status was Active, not recruiting
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Rasmussen Encephalitis |
Drug: Tacrolimus Drug: i.v. immunoglobulins |
Phase 2 Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | 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 |
- 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%). [ Time Frame: until final included subject has been followed for one yer ] [ Designated as safety issue: No ]
- seizure frequency, "Burden of disease" scale, neuropsychological performance, quality of life, T cell receptor studies (H Wiendl, Würzburg) [ Time Frame: until final included subject has been followed for one yer ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 16 |
| Study Start Date: | November 2002 |
| Estimated Study Completion Date: | April 2010 |
| Estimated Primary Completion Date: | April 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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)
|
Drug: Tacrolimus
tacrolimus capsules, 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
Other Name: Prograf
|
|
Experimental: 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).
|
Drug: i.v. immunoglobulins
infusions, 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).
Other Name: Octagam
|
Show Detailed Description Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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.
Exclusion Criteria:
- 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
Contacts and Locations| Germany | |
| University of Bonn, Dept. of Epileptology | |
| Bonn, Germany, 53115 | |
| Principal Investigator: | Christian G Bien, M.D. | University Hospital Bonn, Bonn, Germany |
More Information
Additional Information:
Publications:
| Responsible Party: | PD Dr. Christian G. Bien, MD, University of Bonn, Dept. of Epileptology |
| ClinicalTrials.gov Identifier: | NCT00545493 History of Changes |
| Other Study ID Numbers: | 135/02 |
| Study First Received: | October 16, 2007 |
| Last Updated: | April 9, 2009 |
| Health Authority: | Germany: Federal Institute for Drugs and Medical Devices |
Keywords provided by University Hospital, Bonn:
|
Rasmussen encephalitis Chronic encephalitis Cerebral hemiatrophy Hemiparesis Epilepsy |
Additional relevant MeSH terms:
|
Encephalitis Central Nervous System Viral Diseases Virus Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases Central Nervous System Infections |
Immunoglobulins Antibodies Tacrolimus Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Immunosuppressive Agents |
ClinicalTrials.gov processed this record on June 13, 2013