Autoimmune Diseases, Nervous System, Epilepsy, Cryptogenic, Epilepsy, Partial, Limbic Encephalitis, Seizure Disorder
Conditions
Keywords
Refractory epilepsy, Cryptogenic epilepsy, Autoimmune disorders, IVIG, Immunomodulatory therapy, Autoantibodies
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.
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.
Interventions
DRUGIVIG
IVIG 2 mg/kg in two divided doses with placebo crossover
Sponsors
Baxter Healthcare Corporation
Emory University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immune Abnormalities | Screening visit | neuronal nuclear, cytoplasmic, and cell surface autoantibodies |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects IVIG
IVIG: IVIG 2 mg/kg in two divided doses with placebo crossover | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Immune Abnormalities
neuronal nuclear, cytoplasmic, and cell surface autoantibodies
Time frame: Screening visit
Population: No analysis occurred and study was terminated early due to subject numbers not eligible for the 2nd phase of the study.