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Immunotherapy in Intractable Cryptogenic Epilepsy Patients With Autoimmune Antibody

Primary Purpose

Epilepsy, Unspecified, Intractable

Status
Unknown status
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
IVIG
Prednisolone
Sponsored by
Seoul National University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epilepsy, Unspecified, Intractable focused on measuring Intractable cryptogenic epilepsy with autoimmune antibody, Immunotherapy

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Seoul National University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Immunotherapy

Control

Arm Description

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).

No immunotherapy.

Outcomes

Primary Outcome Measures

Percent seizure reduction

Secondary Outcome Measures

Seizure free rate
Responder rate
Treatment failure rate
Quality of life scores as measured by QOLIE-31
Quality of life scores as measured by BDI-2
Cognition scores as measured by K-MMSE
Amount of epileptiform discharge measured by EEG

Full Information

First Posted
June 18, 2015
Last Updated
February 29, 2016
Sponsor
Seoul National University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02695797
Brief Title
Immunotherapy in Intractable Cryptogenic Epilepsy Patients With Autoimmune Antibody
Official Title
Immunotherapy in Intractable Cryptogenic Epilepsy Patients With Autoimmune Antibody
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Unknown status
Study Start Date
September 2015 (undefined)
Primary Completion Date
December 2016 (Anticipated)
Study Completion Date
December 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seoul National University Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy, Unspecified, Intractable
Keywords
Intractable cryptogenic epilepsy with autoimmune antibody, Immunotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Immunotherapy
Arm Type
Experimental
Arm Description
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).
Arm Title
Control
Arm Type
No Intervention
Arm Description
No immunotherapy.
Intervention Type
Other
Intervention Name(s)
IVIG
Intervention Description
IVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day)
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Intervention Description
IVIG (400mg/kg/day for 5 days) with oral prednisolone (60mg for 5days, than decrease by 10 mg every 2 day)
Primary Outcome Measure Information:
Title
Percent seizure reduction
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Seizure free rate
Time Frame
3 months
Title
Responder rate
Time Frame
3 months
Title
Treatment failure rate
Time Frame
3 months
Title
Quality of life scores as measured by QOLIE-31
Time Frame
3 months
Title
Quality of life scores as measured by BDI-2
Time Frame
3 months
Title
Cognition scores as measured by K-MMSE
Time Frame
3 months
Title
Amount of epileptiform discharge measured by EEG
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kon Chu, Professor
Email
stemcell.snu@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jung-Ah Lim, Fellow
Email
jungah0118@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sang Kun Lee, Professor
Organizational Affiliation
Seoul National University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kon Chu, Professor
Email
stemcell.snu@gmail.com
First Name & Middle Initial & Last Name & Degree
Jung-Ah Lim, Fellow
Email
jungah0118@gmail.com
First Name & Middle Initial & Last Name & Degree
Sang Kun Lee, Professor

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21449936
Citation
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.
Results Reference
background
PubMed Identifier
18339348
Citation
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.
Results Reference
background
PubMed Identifier
24637228
Citation
Dalmau J, Rosenfeld MR. Autoimmune encephalitis update. Neuro Oncol. 2014 Jun;16(6):771-8. doi: 10.1093/neuonc/nou030. Epub 2014 Mar 16.
Results Reference
background
PubMed Identifier
24176648
Citation
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.
Results Reference
background
PubMed Identifier
23290630
Citation
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.
Results Reference
background
PubMed Identifier
24829602
Citation
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.
Results Reference
background
PubMed Identifier
24662003
Citation
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.
Results Reference
background
PubMed Identifier
19780798
Citation
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.
Results Reference
background
PubMed Identifier
16870397
Citation
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.
Results Reference
background
PubMed Identifier
19817821
Citation
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.
Results Reference
background
PubMed Identifier
10891904
Citation
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.
Results Reference
background
PubMed Identifier
23646971
Citation
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.
Results Reference
background
PubMed Identifier
24706013
Citation
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.
Results Reference
background
PubMed Identifier
23464826
Citation
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.
Results Reference
background
PubMed Identifier
25112548
Citation
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.
Results Reference
background

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Immunotherapy in Intractable Cryptogenic Epilepsy Patients With Autoimmune Antibody

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