NCT01545518

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Nov 2011

Geographic Reach
1 country

2 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2011

Completed
29 days until next milestone

First Submitted

Initial submission to the registry

November 30, 2011

Completed
3 months until next milestone

First Posted

Study publicly available on registry

March 6, 2012

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2013

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2013

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

September 1, 2014

Completed
Last Updated

September 1, 2014

Status Verified

August 1, 2014

Enrollment Period

1.6 years

First QC Date

November 30, 2011

Results QC Date

August 21, 2014

Last Update Submit

August 21, 2014

Conditions

Epilepsy, CryptogenicEpilepsy, PartialSeizure DisorderAutoimmune Diseases, Nervous SystemLimbic Encephalitis

Keywords

Refractory epilepsyCryptogenic epilepsyAutoimmune disordersIVIGImmunomodulatory therapyAutoantibodies

Outcome Measures

Primary Outcomes (1)

  • Immune Abnormalities

    neuronal nuclear, cytoplasmic, and cell surface autoantibodies

    Screening visit

Study Arms (1)

all subjects

EXPERIMENTAL

IVIG

Drug: IVIG

Interventions

IVIGDRUG

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

Also known as: IVIG manufactured by Baxter Healthcare Corporation
all subjects

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

The Emory Clinic, Inc.

Atlanta, Georgia, 30322, United States

Location

Related Publications (14)

  • Alamowitch S, Graus F, Uchuya M, Rene R, Bescansa E, Delattre JY. Limbic encephalitis and small cell lung cancer. Clinical and immunological features. Brain. 1997 Jun;120 ( Pt 6):923-8. doi: 10.1093/brain/120.6.923.

    PMID: 9217677BACKGROUND

  • Graus F, Keime-Guibert F, Rene 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. doi: 10.1093/brain/124.6.1138.

    PMID: 11353730BACKGROUND

  • 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. doi: 10.1093/brain/123.7.1481.

    PMID: 10869059BACKGROUND

  • 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. doi: 10.1016/s0022-510x(03)00130-8.

    PMID: 12873758BACKGROUND

  • 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. doi: 10.4065/78.11.1363.

    PMID: 14601695BACKGROUND

  • 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. doi: 10.1212/wnl.50.3.652.

    PMID: 9521251BACKGROUND

  • 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.

    PMID: 19204167BACKGROUND

  • 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.

    PMID: 18195661BACKGROUND

  • Pittock SJ, Kryzer TJ, Lennon VA. Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol. 2004 Nov;56(5):715-9. doi: 10.1002/ana.20269.

    PMID: 15468074BACKGROUND

  • Porta-Etessam J, Ruiz-Morales J, Millan JM, Ramos A, Martinez-Salio A, Berbel-Garcia 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. doi: 10.1046/j.1468-1331.2001.00213.x. No abstract available.

    PMID: 11422434BACKGROUND

  • 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. doi: 10.1002/1531-8249(199902)45:23.0.co;2-n.

    PMID: 9989630BACKGROUND

  • 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. doi: 10.1212/01.wnl.0000122648.19196.02.

    PMID: 15079019BACKGROUND

  • 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. doi: 10.1593/neo.07322.

    PMID: 17898866BACKGROUND

  • 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.

    PMID: 21570256BACKGROUND

MeSH Terms

Conditions

EpilepsyEpilepsies, PartialAutoimmune Diseases of the Nervous SystemLimbic EncephalitisDrug Resistant EpilepsyAutoimmune Diseases

Interventions

Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Brain DiseasesCentral Nervous System DiseasesNervous System DiseasesImmune System DiseasesCentral Nervous System Viral DiseasesCentral Nervous System InfectionsInfectionsParaneoplastic Syndromes, Nervous SystemNervous System NeoplasmsNeoplasms by SiteNeoplasmsParaneoplastic SyndromesEncephalitisNeurodegenerative DiseasesNeuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin GImmunoglobulin IsotypesAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Limitations and Caveats

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

Results Point of Contact

Title
Dr. Charles M. Epstein
Organization
Emory University
cepstei@emory.edu
404-778-3633

Study Officials

  • Charles M. Epstein, M.D.

    Emory University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professsor of Neurology - Divsion of Epilepsy

Study Record Dates

First Submitted

November 30, 2011

First Posted

March 6, 2012

Study Start

November 1, 2011

Primary Completion

June 1, 2013

Study Completion

August 1, 2013

Last Updated

September 1, 2014

Results First Posted

September 1, 2014

Record last verified: 2014-08

Locations

US(2)