Pilot Trial to Evaluate The Effect of Oral Methylprednisolone on Seizure Frequency in Children With Epilepsy

Study Overview
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Brief Summary
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Although corticosteroids have been shown to be beneficial anecdotally for refractory epilepsy, the effects of corticosteroids on pediatric epilepsy have primarily been studied retrospectively amongst a heterogeneous patient population. The objective of this prospective cross-over study is to determine the effect of oral steroids on convulsive seizure frequency and evaluate the tolerability of pulsed oral steroids. Participants will be prospectively enrolled from pediatric neurology clinic at Children's Hospital of New Orleans, and baseline seizure frequency will be assessed. Participants will then be randomized to receive either the study drug, methylprednisolone, or placebo during the first month, followed by a one-month wash-out period. During the third month of the study, participants will enter the cross-over phase of the study where those who received methylprednisolone will receive placebo, and those who received placebo will receive methylprednisolone. The primary outcome will be the percentage of patients with 50% or more reduction in seizure frequency following one course of oral methylprednisolone. frequency following 1 course of oral methylprednisolone.

Official Title
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Pilot Randomized, Placebo-Controlled Trial to Evaluate The Effect of Oral Pulsed Methylprednisolone on Seizure Frequency in Pediatric Patients With Idiopathic Intractable Convulsive Epilepsy

Conditions
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Intractable Epilepsy, Convulsive Seizures

Intervention / Treatment
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* Drug: methylprednisolone sodium succinate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients age 2 -18 years of age Patients who have at least 4 convulsive (generalized tonic or tonic-clonic) seizures per month on 2 or more anti-epileptic drugs (AEDs) at therapeutic doses a. Epilepsy diagnosed by historical clinical evidence Family's ability to understand and willingness to sign a written informed consent document for patients under 18. Willingness to complete seizure diary for duration of study Willingness to present to all study visits Exclusion Criteria: Patients with history of the following diagnoses: Traumatic brain injury Tuberous sclerosis Sturge Weber Cortical dysplasia Patients with known hereditary degenerative diseases as follows: Adrenoleukodystrophy Neuronal ceroid lipofuscinosis Leigh Syndrome Myoclonic epilepsy with ragged red fibers (MERRF) Rett Syndrome Patients with the following epilepsy syndromes Infantile spasms West Syndrome Progressive myoclonic epilepsy Dravet syndrome Doose syndrome Ohtahara syndrome Rasmussen's encephalitis Patients with the following metabolic disorders Phenylketonuria Maple syrup urine disease Organic acidemias Galactosemia Peroxismal disorders (e.g. Zellwegers) Lysosomal disorders Urea cycle disorders Patients with history of immunodeficiency Patients with the following infections HIV/AIDS Active or latent TB Active or suspected bacterial infection Active, latent or suspected fungemia Active or suspected parasitic infection Patients with history of malignancy Patients with history of or active myopathy Patients with degenerative neuromuscular disorders Patients with history of hypersensitivity or allergic reactions to corticosteroids Patients with history of psychosis Patients with diabetes mellitus Pregnancy Any underlying predisposition to gastrointestinal bleeding (peptic ulcer disease, gastritis, colitis)

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional start<br>Patients who randomize to the interventional start arm will receive the study drug, methylprednisolone sodium succinate, in the first month of the study, followed by placebo in the cross-over phase of the study. | Drug: methylprednisolone sodium succinate<br>* Methylprednisolone sodium succinate will be re-constituted in simple syrup in a concentration of 80mg/mL and will be administered orally at 20mg/kg (max 1000mg) for days 1, 2, and 3 of the intervention phase of the study.<br>Other: Placebo<br>* The placebo used in this study will be simple syrup.<br>|
| Placebo Comparator: Placebo start<br>Patients who randomize to the placebo start arm will receive placebo in the first month of the study, followed by the study drug, methylprednisolone sodium succinate, in the cross-over phase of the study. | Drug: methylprednisolone sodium succinate<br>* Methylprednisolone sodium succinate will be re-constituted in simple syrup in a concentration of 80mg/mL and will be administered orally at 20mg/kg (max 1000mg) for days 1, 2, and 3 of the intervention phase of the study.<br>Other: Placebo<br>* The placebo used in this study will be simple syrup.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seizure frequency | The percentage of patients with 50% or more reduction in seizure frequency. | The number of seizures per month will be assessed at 1 month (following placebo/intervention), 2 months (following wash-out), and 3 months (following cross-over phase of placebo/intervention). Change compared to baseline will be calculated. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seizure freedom | The percentage of participants who become seizure free over 1 month | The number of seizures per month will be assessed at 1 month (following placebo/intervention), 2 months (following wash-out period), and 3 months (following cross-over phase of placebo/intervention). | 
| Adverse events | Percentage of participants who reports adverse events and the severity of the adverse events. | Adverse events will be recorded at 1 month (following placebo/intervention), 2 months (following wash-out period), and 3 months (following cross-over phase of placebo/intervention). | 
| Drop out percentage | Percentage of participants who drop out of the study due to adverse events | The number of participants who drop out will be counted and recorded at 1 month (following placebo/intervention), 2 months (following wash-out period), and 3 months (following cross-over phase of placebo/intervention). |