Immunotherapy in Intractable Cryptogenic Epilepsy Patients With Autoimmune Antibody

NCT ID: NCT02695797

Last Updated: 2016-03-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-09-30

Study Completion Date

2016-12-31

Brief Summary

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The purpose of the study is to investigate effect of immunotherapy in intractable cryptogenic epilepsy patients with autoimmune antibody.

Detailed Description

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Cryptogenic epilepsy is an epilepsy of presumed symptomatic nature but the cause has not been identified. It account for at least 40% of adult-onset epilepsy. Autoimmune encephalitis including classic paraneoplastic syndrome and autoimmune synaptic encephalitis is a new category of immune-mediated disorders which often has favorable outcome. Recent studies reported that immunotherapy improves seizure outcome in medically intractable epilepsy patients with clinical and serological evidence of an autoimmune basis. Neural autoantibodies were detected in 22% of epilepsy due to unknown cause in a study, mostly from the antiepileptic drug(AED)-resistant epilepsy group. Of the patients who received immunotherapy, 75% archived \>50% reduction in seizure frequency.

Many patients with cryptogenic epilepsy are refractory to AED and significant percent of cryptogenic epilepsy harbor neural autoantibody. In those cases, immunotherapy is suggestive based on favorable outcome of immunotherapy in autoimmune encephalitis and autoimmune epilepsy. Investigators aim to investigate the response to immunotherapy in intractable cryptogenic epilepsy patients with neural autoantibodies.

Conditions

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Epilepsy, Unspecified, Intractable

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Immunotherapy

Intravenous immunoglobulin (IVIG) and oral prednisolone. IVIG and oral prednisolone are administered simultaneously: IVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day).

Group Type EXPERIMENTAL

IVIG

Intervention Type OTHER

IVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day)

Prednisolone

Intervention Type DRUG

IVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day)

Control

No immunotherapy.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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IVIG

IVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day)

Intervention Type OTHER

Prednisolone

IVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* A diagnosis of cryptogenic epilepsy according to the International League Against Epilepsy's Classification of Epilepsy.
* Intractable epilepsy: Complete seizure control is not achieved with trials of two appropriate antiepileptic drugs
* At least 1 seizure within the past 8 weeks
* Presence of autoimmune antibody (NMDAR, LGI1, CASPR2, AMPA1, AMPA2, GABAB-R, anti-Hu, -Yo, -Ri, -Ma2, -CV2/CRMP5, -amphiphysin, GAD) in serum or cerebrospinal fluid
* Written informed consent signed by the subject or legal guardian prior to entering the study

Exclusion Criteria

* Clinical evidence of autoimmune encephalitis such as autoimmune limbic encephalitis
* History of severe head trauma
* Presence of structural abnormality which is thought to be epileptogenic in brain MRI
* Epilepsy of predominantly genetic or presumed genetic origin
* An active CNS infection, demyelinating disease, degenerative neurologic disease or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results History of immunotherapy
* A history of nonepileptic or psychogenic seizures within past 1 year
* Any clinically significant laboratory abnormality that in the opinion of the Investigator would exclude the subject from the study
* Any clinically significant psychiatric illness, psychological, or behavioral problems that, in the opinion of the Investigator, would interfere with the subject's ability to participate in the study
* Recent (within 4 weeks) change or dose adjustment of anti-epileptic drug (1 to 2 doses of rescue benzodiazepine is permitted)
* Refuse to participate in the study
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Seoul National University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Sang Kun Lee

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sang Kun Lee, Professor

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital

Locations

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Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Countries

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South Korea

Central Contacts

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Kon Chu, Professor

Role: CONTACT

Jung-Ah Lim, Fellow

Role: CONTACT

Facility Contacts

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Kon Chu, Professor

Role: primary

Jung-Ah Lim, Fellow

Role: backup

References

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Shorvon SD. The etiologic classification of epilepsy. Epilepsia. 2011 Jun;52(6):1052-7. doi: 10.1111/j.1528-1167.2011.03041.x. Epub 2011 Mar 30.

Reference Type BACKGROUND
PMID: 21449936 (View on PubMed)

Dalmau J, Rosenfeld MR. Paraneoplastic syndromes of the CNS. Lancet Neurol. 2008 Apr;7(4):327-40. doi: 10.1016/S1474-4422(08)70060-7.

Reference Type BACKGROUND
PMID: 18339348 (View on PubMed)

Dalmau J, Rosenfeld MR. Autoimmune encephalitis update. Neuro Oncol. 2014 Jun;16(6):771-8. doi: 10.1093/neuonc/nou030. Epub 2014 Mar 16.

Reference Type BACKGROUND
PMID: 24637228 (View on PubMed)

Shin YW, Lee ST, Shin JW, Moon J, Lim JA, Byun JI, Kim TJ, Lee KJ, Kim YS, Park KI, Jung KH, Lee SK, Chu K. VGKC-complex/LGI1-antibody encephalitis: clinical manifestations and response to immunotherapy. J Neuroimmunol. 2013 Dec 15;265(1-2):75-81. doi: 10.1016/j.jneuroim.2013.10.005. Epub 2013 Oct 17.

Reference Type BACKGROUND
PMID: 24176648 (View on PubMed)

Titulaer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013 Feb;12(2):157-65. doi: 10.1016/S1474-4422(12)70310-1. Epub 2013 Jan 3.

Reference Type BACKGROUND
PMID: 23290630 (View on PubMed)

Lim JA, Lee ST, Jung KH, Kim S, Shin JW, Moon J, Byun JI, Kim TJ, Shin YW, Lee KJ, Kim YS, Park KI, Lee SK, Chu K. Anti-N-methyl-d-aspartate receptor encephalitis in Korea: clinical features, treatment, and outcome. J Clin Neurol. 2014 Apr;10(2):157-61. doi: 10.3988/jcn.2014.10.2.157. Epub 2014 Apr 23.

Reference Type BACKGROUND
PMID: 24829602 (View on PubMed)

Kim TJ, Lee ST, Shin JW, Moon J, Lim JA, Byun JI, Shin YW, Lee KJ, Jung KH, Kim YS, Park KI, Chu K, Lee SK. Clinical manifestations and outcomes of the treatment of patients with GABAB encephalitis. J Neuroimmunol. 2014 May 15;270(1-2):45-50. doi: 10.1016/j.jneuroim.2014.02.011. Epub 2014 Feb 28.

Reference Type BACKGROUND
PMID: 24662003 (View on PubMed)

Barajas RF, Collins DE, Cha S, Geschwind MD. Adult-onset drug-refractory seizure disorder associated with anti-voltage-gated potassium-channel antibody. Epilepsia. 2010 Mar;51(3):473-7. doi: 10.1111/j.1528-1167.2009.02287.x. Epub 2009 Sep 22.

Reference Type BACKGROUND
PMID: 19780798 (View on PubMed)

Majoie HJ, de Baets M, Renier W, Lang B, Vincent A. Antibodies to voltage-gated potassium and calcium channels in epilepsy. Epilepsy Res. 2006 Oct;71(2-3):135-41. doi: 10.1016/j.eplepsyres.2006.06.003. Epub 2006 Jul 25.

Reference Type BACKGROUND
PMID: 16870397 (View on PubMed)

Liimatainen S, Peltola M, Sabater L, Fallah M, Kharazmi E, Haapala AM, Dastidar P, Knip M, Saiz A, Peltola J. Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy. Epilepsia. 2010 May;51(5):760-7. doi: 10.1111/j.1528-1167.2009.02325.x. Epub 2009 Oct 8.

Reference Type BACKGROUND
PMID: 19817821 (View on PubMed)

Peltola J, Kulmala P, Isojarvi J, Saiz A, Latvala K, Palmio J, Savola K, Knip M, Keranen T, Graus F. Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy. Neurology. 2000 Jul 12;55(1):46-50. doi: 10.1212/wnl.55.1.46.

Reference Type BACKGROUND
PMID: 10891904 (View on PubMed)

Bien CG. Value of autoantibodies for prediction of treatment response in patients with autoimmune epilepsy: review of the literature and suggestions for clinical management. Epilepsia. 2013 May;54 Suppl 2:48-55. doi: 10.1111/epi.12184.

Reference Type BACKGROUND
PMID: 23646971 (View on PubMed)

Toledano M, Britton JW, McKeon A, Shin C, Lennon VA, Quek AM, So E, Worrell GA, Cascino GD, Klein CJ, Lagerlund TD, Wirrell EC, Nickels KC, Pittock SJ. Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy. Neurology. 2014 May 6;82(18):1578-86. doi: 10.1212/WNL.0000000000000383. Epub 2014 Apr 4.

Reference Type BACKGROUND
PMID: 24706013 (View on PubMed)

Brenner T, Sills GJ, Hart Y, Howell S, Waters P, Brodie MJ, Vincent A, Lang B. Prevalence of neurologic autoantibodies in cohorts of patients with new and established epilepsy. Epilepsia. 2013 Jun;54(6):1028-35. doi: 10.1111/epi.12127. Epub 2013 Mar 6.

Reference Type BACKGROUND
PMID: 23464826 (View on PubMed)

Iorio R, Assenza G, Tombini M, Colicchio G, Della Marca G, Benvenga A, Damato V, Rossini PM, Vollono C, Plantone D, Marti A, Batocchi AP, Evoli A. The detection of neural autoantibodies in patients with antiepileptic-drug-resistant epilepsy predicts response to immunotherapy. Eur J Neurol. 2015 Jan;22(1):70-8. doi: 10.1111/ene.12529. Epub 2014 Aug 12.

Reference Type BACKGROUND
PMID: 25112548 (View on PubMed)

Other Identifiers

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1504102666

Identifier Type: -

Identifier Source: org_study_id

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