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

NCT00545493 | Unknown Phase 2

• 1 other identifier: 135/02
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Rasmussen Encephalitis

Keywords

Rasmussen encephalitis; Chronic encephalitis; Cerebral hemiatrophy; Hemiparesis; Epilepsy

Outcome Measures

Primary Outcomes (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%).

  until final included subject has been followed for one yer

Secondary Outcomes (1)

• 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

Study Arms (2)

Group 1

EXPERIMENTAL

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

Group 2

EXPERIMENTAL

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

Interventions

Tacrolimus DRUG

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

Also known as: Prograf

Group 1

i.v. immunoglobulins DRUG

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).

Also known as: Octagam

Group 2

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients meeting at least two of the following three criteria:
• Clinical: Epilepsia partialis continua or progressive\* hemiparesis
• MRI: Progressive\* cerebral hemiatrophy
• "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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Hospital, Bonn: lead
• Octapharma: collaborator
• Astellas Pharma GmbH: collaborator

Study Sites (1)

University of Bonn, Dept. of Epileptology

Bonn, 53115, Germany

Location

Related Publications (4)

• Bien CG, Gleissner U, Sassen R, Widman G, Urbach H, Elger CE. An open study of tacrolimus therapy in Rasmussen encephalitis. Neurology. 2004 Jun 8;62(11):2106-9. doi: 10.1212/01.wnl.0000128044.94294.87.

  PMID: 15184626 BACKGROUND

• Bien CG, Granata T, Antozzi C, Cross JH, Dulac O, Kurthen M, Lassmann H, Mantegazza R, Villemure JG, Spreafico R, Elger CE. Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement. Brain. 2005 Mar;128(Pt 3):454-71. doi: 10.1093/brain/awh415. Epub 2005 Feb 2.

  PMID: 15689357 BACKGROUND

• Granata T, Fusco L, Gobbi G, Freri E, Ragona F, Broggi G, Mantegazza R, Giordano L, Villani F, Capovilla G, Vigevano F, Bernardina BD, Spreafico R, Antozzi C. Experience with immunomodulatory treatments in Rasmussen's encephalitis. Neurology. 2003 Dec 23;61(12):1807-10. doi: 10.1212/01.wnl.0000099074.04539.e0.

  PMID: 14694056 BACKGROUND

• Hart YM, Cortez M, Andermann F, Hwang P, Fish DR, Dulac O, Silver K, Fejerman N, Cross H, Sherwin A, et al. Medical treatment of Rasmussen's syndrome (chronic encephalitis and epilepsy): effect of high-dose steroids or immunoglobulins in 19 patients. Neurology. 1994 Jun;44(6):1030-6. doi: 10.1212/wnl.44.6.1030.

  PMID: 8208394 BACKGROUND

Related Links

• Homepage of institution performing the trial

MeSH Terms

Conditions

Encephalitis; Paresis; Epilepsy

Interventions

Tacrolimus; Octagam

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Christian G Bien, M.D.

  University Hospital Bonn, Bonn, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 16, 2007
• First Posted: October 17, 2007
• Study Start: November 1, 2002
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: April 10, 2009

Record last verified: 2009-04

Locations

DE (1)