IVIG Treatment for Refractory Immune-Related Adult Epilepsy

• Sponsor: Emory University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01545518
• Collaborator: Baxter Healthcare Corporation (Industry)
• Enrollment: 20
• Locations: 2
• Arm: 1
• Duration (Months): 21
• Patients Per Site: 10
• Patients Per Site Per Month: 0.5

Study Details

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
• Actual Enrollment: 20 participants
• Allocation: N/A
• 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: Nov 1, 2011
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Immune Abnormalities [Screening visit]

   neuronal nuclear, cytoplasmic, and cell surface autoantibodies

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Grady Memorial Hospital	Atlanta	Georgia	United States	30303
2	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

Study Documents (Full-Text)

None provided.

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.
• 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.
• 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.
• 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.
• 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.

• Responsible Party: Charles M. Epstein, MD, Professsor of Neurology - Divsion of Epilepsy, Emory University
• ClinicalTrials.gov Identifier: NCT01545518
• Other Study ID Numbers: IRB00052646; BT11-000312
• First Posted: Mar 6, 2012
• Last Update Posted: Sep 1, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by Charles M. Epstein, MD, Professsor of Neurology - Divsion of Epilepsy, Emory University: Refractory epilepsy; Cryptogenic epilepsy; Autoimmune disorders; IVIG; Immunomodulatory therapy; Autoantibodies
• Additional relevant MeSH terms: Limbic Encephalitis; Epilepsy; Seizures; Encephalitis; Epilepsies, Partial; Nervous System Diseases; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Immunoglobulins, Intravenous

Study Results

Participant Flow

Recruitment Details	Patients enrolled in a medical setting if eligible. Inclusion and exclusion criteria. A total of 20 patients with unexplained refractory epilepsy were screened and tested with a multiple panel for anti-neuronal antibodies.
Pre-assignment Detail	In comparisons with our original futility criteria, it was apparent that the absence of more powerful findings, and the time it took to collect the ones we have, indicated the virtual impossibility of identifying enough patients with strong autoimmune findings to carry out Phase 2 of this study.

Arm/Group Title	All Subjects
Arm/Group Description	IVIG IVIG: IVIG 2 mg/kg in two divided doses with placebo crossover
Period Title: Overall Study
STARTED	20
COMPLETED	20
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Subjects
Arm/Group Description	IVIG IVIG: IVIG 2 mg/kg in two divided doses with placebo crossover
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	20 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	11 55%
Male	9 45%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Immune Abnormalities
Description	neuronal nuclear, cytoplasmic, and cell surface autoantibodies
Time Frame	Screening visit

Outcome Measure Data

Analysis Population Description

No analysis occurred and study was terminated early due to subject numbers not eligible for the 2nd phase of the study.

Arm/Group Title	All Subjects
Arm/Group Description	IVIG IVIG: IVIG 2 mg/kg in two divided doses with placebo crossover
Measure Participants	0

Adverse Events

Arm/Group Title	All Subjects
Arm/Group Description	IVIG IVIG: IVIG 2 mg/kg in two divided doses with placebo crossover No AE's.
All Cause Mortality
	All Subjects
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Subjects
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Other (Not Including Serious) Adverse Events
	All Subjects
	Affected / at Risk (%)	# Events
Total	0/20 (0%)

Limitations/Caveats

Study was terminated early. Subject eligibility for phase 2 not available.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.