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Efficacy of Tacrolimus and I.V.-Immunoglobulins in Rasmussen Encephalitis

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ClinicalTrials.gov Identifier: NCT00545493
Recruitment Status : Unknown
Verified April 2009 by University Hospital, Bonn.
Recruitment status was:  Active, not recruiting
First Posted : October 17, 2007
Last Update Posted : April 10, 2009
Astellas Pharma GmbH
Information provided by:
University Hospital, Bonn

Brief Summary:
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 or disease Intervention/treatment Phase
Rasmussen Encephalitis Drug: Tacrolimus Drug: i.v. immunoglobulins Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : November 2002
Estimated Primary Completion Date : April 2010
Estimated Study Completion Date : April 2010

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients meeting at least two of the following three criteria:

    1. Clinical: Epilepsia partialis continua or progressive* hemiparesis
    2. MRI: Progressive* cerebral hemiatrophy
    3. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00545493

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University of Bonn, Dept. of Epileptology
Bonn, Germany, 53115
Sponsors and Collaborators
University Hospital, Bonn
Astellas Pharma GmbH
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Principal Investigator: Christian G Bien, M.D. University Hospital Bonn, Bonn, Germany
Additional Information:
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Responsible Party: PD Dr. Christian G. Bien, MD, University of Bonn, Dept. of Epileptology
ClinicalTrials.gov Identifier: NCT00545493    
Other Study ID Numbers: 135/02
First Posted: October 17, 2007    Key Record Dates
Last Update Posted: April 10, 2009
Last Verified: April 2009
Keywords provided by University Hospital, Bonn:
Rasmussen encephalitis
Chronic encephalitis
Cerebral hemiatrophy
Additional relevant MeSH terms:
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Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Pathologic Processes
Immunoglobulins, Intravenous
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action