IVIG Treatment for Refractory Immune-Related Adult Epilepsy

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ClinicalTrials.gov Identifier: NCT01545518

Recruitment Status : Terminated (Futility criteria, unable for Phase 2 of study, & phase 1 was terminated.)

First Posted : March 6, 2012

Results First Posted : September 1, 2014

Last Update Posted : September 1, 2014

Sponsor:

Collaborator:

Baxter Healthcare Corporation

Information provided by (Responsible Party):

Charles M. Epstein, MD, Emory University

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Epilepsy, Cryptogenic Epilepsy, Partial Seizure Disorder Autoimmune Diseases, Nervous System Limbic Encephalitis	Drug: IVIG	Phase 2

Detailed 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.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	20 participants
Intervention Model:	Single Group Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	IVIG Treatment for Refractory Immune-Related Adult Epilepsy
Study Start Date :	November 2011
Actual Primary Completion Date :	June 2013
Actual Study Completion Date :	August 2013

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Autosomal dominant partial epilepsy with auditory features Pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Epilepsy

Genetic and Rare Diseases Information Center resources: Limbic Encephalitis

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: all subjects IVIG	Drug: IVIG IVIG 2 mg/kg in two divided doses with placebo crossover Other Name: IVIG manufactured by Baxter Healthcare Corporation

Outcome Measures

Primary Outcome Measures :

Immune Abnormalities [ Time Frame: Screening visit ]
neuronal nuclear, cytoplasmic, and cell surface autoantibodies

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 50 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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): NCT01545518

Locations


United States, Georgia
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
The Emory Clinic, Inc.
Atlanta, Georgia, United States, 30322

Sponsors and Collaborators

Emory University

Baxter Healthcare Corporation

Investigators


Principal Investigator:	Charles M. Epstein, M.D.	Emory University

More Information

Publications:

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.

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.

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.

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.

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.

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.

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].

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.

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

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.

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.

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.

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.

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.


Responsible Party:	Charles M. Epstein, MD, Professsor of Neurology - Divsion of Epilepsy, Emory University
ClinicalTrials.gov Identifier:	NCT01545518 History of Changes
Other Study ID Numbers:	IRB00052646 BT11-000312 ( Other Identifier: Other )
First Posted:	March 6, 2012 Key Record Dates
Results First Posted:	September 1, 2014
Last Update Posted:	September 1, 2014
Last Verified:	August 2014

Keywords provided by Charles M. Epstein, MD, Emory University:


Refractory epilepsy Cryptogenic epilepsy Autoimmune disorders	IVIG Immunomodulatory therapy Autoantibodies

Additional relevant MeSH terms:


Epilepsy Epilepsies, Partial Seizures Encephalitis Autoimmune Diseases Nervous System Diseases Limbic Encephalitis Autoimmune Diseases of the Nervous System Brain Diseases Central Nervous System Diseases Neurologic Manifestations Signs and Symptoms Immune System Diseases	Paraneoplastic Syndromes, Nervous System Nervous System Neoplasms Neoplasms by Site Neoplasms Paraneoplastic Syndromes Central Nervous System Viral Diseases Central Nervous System Infections Neurodegenerative Diseases Immunoglobulins, Intravenous gamma-Globulins Rho(D) Immune Globulin Immunologic Factors Physiological Effects of Drugs

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