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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2009 by University Hospital, Bonn.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Octapharma
Astellas Pharma GmbH
Information provided by:
University Hospital, Bonn
ClinicalTrials.gov Identifier:
NCT00545493
First received: October 16, 2007
Last updated: April 9, 2009
Last verified: April 2009
  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

Resource links provided by NLM:


Further study details as provided by University Hospital, Bonn:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00545493

Locations
Germany
University of Bonn, Dept. of Epileptology
Bonn, Germany, 53115
Sponsors and Collaborators
University Hospital, Bonn
Octapharma
Astellas Pharma GmbH
Investigators
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
Brain Diseases
Central Nervous System Diseases
Central Nervous System Infections
Central Nervous System Viral Diseases
Nervous System Diseases
Virus Diseases
Antibodies
Immunoglobulins
Tacrolimus
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014