IVIG Treatment for Refractory Immune-Related Adult Epilepsy

Seizure Disorder Clinical Trial

Official title:

IVIG Treatment for Refractory Immune-Related Adult Epilepsy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01545518
• Other study ID #: IRB00052646
• Secondary ID: BT11-000312
• Status: Terminated
• Phase: Phase 2
• First received: November 30, 2011
• Last updated: August 21, 2014
• Start date: November 2011
• Est. completion date: August 2013

Study information

• Verified date: August 2014
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of the initial screening study is to find out if immune problems are an unrecognized cause of epilepsy in some patients. This study consists of a single blood sample, which will be tested for possible immune abnormalities. If enough patients are found who show immune abnormalities, those patients who are still having uncontrolled seizures will be invited to participate in a study of immune treatment with a compound called intravenous immunoglobulin (IVIG).

The study hypothesis is that a significant proportion of the young-onset, refractory, image-negative, partial-onset epilepsy population have an underlying autoimmune disorder, and many of these patients will respond to immune therapies, including IVIG.

At present, the importance of immune abnormalities in causing epilepsy, and the proper treatment when they are found, are both poorly understood. The investigators hope that this study will help us understand the cause of some cases that are difficult to treat.

Description:

The study is divided into two phases:

Phase I: The investigators will screen for evidence of neuronal nuclear, cytoplasmic, and cell surface autoantibodies in our population of new onset refractory, imaging-negative young adult epilepsy patients. This part of the study involves obtaining a single blood sample, equal to about 2 teaspoons.

Phase 2: If a sufficient number of cases are identified, a double-blind crossover study of IVIG treatment will be performed in these patients.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: August 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Diagnosis of uncontrolled epilepsy with at least two seizures a month for three consecutive months.

• Age 18 to 50.

• Clinical semiology or electroencephalogram (EEG) consistent with partial onset epilepsy.

• Refractory to an adequate trial of two or more main-line anti-epileptic drugs.

• Ability to keep a seizure diary.

• Normal brain magnetic resonance imaging (MRI) - 3 Tesla, seizure protocol; with the exception of hippocampal sclerosis

Exclusion Criteria:

• History of severe prematurity or neonatal distress, febrile seizures, moderate or sever traumatic brain injury, stroke, brain tumor, meningitis, encephalitis, neurocutaneous syndromes, or intracranial metal objects.

• Evidence of psychogenic epilepsy.

• History of convulsive status epilepticus.

• History of primary generalized epilepsy in a first degree relative.

• Known serious medical illness.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Autoimmune Diseases
• Autoimmune Diseases of the Nervous System
• Autoimmune Diseases, Nervous System
• Encephalitis
• Epilepsies, Partial
• Epilepsy
• Epilepsy, Cryptogenic
• Epilepsy, Partial
• Limbic Encephalitis
• Nervous System Diseases
• Seizure Disorder

Intervention

Drug:
• IVIG
IVIG 2 mg/kg in two divided doses with placebo crossover

Locations

Country	Name	City	State
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	The Emory Clinic, Inc.	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	Baxter Healthcare Corporation

Country where clinical trial is conducted

United States, 

References & Publications (14)

Alamowitch S, Graus F, Uchuya M, Reñé R, Bescansa E, Delattre JY. Limbic encephalitis and small cell lung cancer. Clinical and immunological features. Brain. 1997 Jun;120 ( Pt 6):923-8. — View Citation

Graus F, Keime-Guibert F, Reñe R, Benyahia B, Ribalta T, Ascaso C, Escaramis G, Delattre JY. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain. 2001 Jun;124(Pt 6):1138-48. — View Citation

Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 2000 Jul;123 ( Pt 7):1481-94. — View Citation

Jacobs DA, Fung KM, Cook NM, Schalepfer WW, Goldberg HI, Stecker MM. Complex partial status epilepticus associated with anti-Hu paraneoplastic syndrome. J Neurol Sci. 2003 Sep 15;213(1-2):77-82. — View Citation

Lawn ND, Westmoreland BF, Kiely MJ, Lennon VA, Vernino S. Clinical, magnetic resonance imaging, and electroencephalographic findings in paraneoplastic limbic encephalitis. Mayo Clin Proc. 2003 Nov;78(11):1363-8. — View Citation

Lucchinetti CF, Kimmel DW, Lennon VA. Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology. 1998 Mar;50(3):652-7. — View Citation

Matarasso N, Bar-Shira A, Rozovski U, Rosner S, Orr-Urtreger A. Functional analysis of the Aurora Kinase A Ile31 allelic variant in human prostate. Neoplasia. 2007 Sep;9(9):707-15. — View Citation

McKeon A, Ahlskog JE, Britton JW, Lennon VA, Pittock SJ. Reversible extralimbic paraneoplastic encephalopathies with large abnormalities on magnetic resonance images. Arch Neurol. 2009 Feb;66(2):268-71. doi: 10.1001/archneurol.2008.556. Erratum in: Arch Neurol. 2011 Mar;68(3):371. Britton, Jeffrey A [corrected to Britton, Jeffrey W]. — View Citation

Nahab F, Heller A, Laroche SM. Focal cortical resection for complex partial status epilepticus due to a paraneoplastic encephalitis. Neurologist. 2008 Jan;14(1):56-9. doi: 10.1097/NRL.0b013e3181578952. — View Citation

Pittock SJ, Kryzer TJ, Lennon VA. Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol. 2004 Nov;56(5):715-9. — View Citation

Porta-Etessam J, Ruiz-Morales J, Millan JM, Ramos A, Martínez-Salio A, Berbel-García A. Epilepsia partialis continua and frontal features as a debut of anti-Hu paraneoplastic encephalomyelitis with focal frontal encephalitis. Eur J Neurol. 2001 Jul;8(4):359-60. — View Citation

Rudzinski LA, Pittock SJ, McKeon A, Lennon VA, Britton JW. Extratemporal EEG and MRI findings in ANNA-1 (anti-Hu) encephalitis. Epilepsy Res. 2011 Aug;95(3):255-62. doi: 10.1016/j.eplepsyres.2011.04.006. Epub 2011 May 12. — View Citation

Shavit YB, Graus F, Probst A, Rene R, Steck AJ. Epilepsia partialis continua: a new manifestation of anti-Hu-associated paraneoplastic encephalomyelitis. Ann Neurol. 1999 Feb;45(2):255-8. — View Citation

Thieben MJ, Lennon VA, Boeve BF, Aksamit AJ, Keegan M, Vernino S. Potentially reversible autoimmune limbic encephalitis with neuronal potassium channel antibody. Neurology. 2004 Apr 13;62(7):1177-82. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immune Abnormalities	neuronal nuclear, cytoplasmic, and cell surface autoantibodies	Screening visit	No