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

Phase 1

• Conditions: Intractable Epilepsy; Convulsive Seizures
• Interventions: Drug: methylprednisolone sodium succinate; Other: Placebo

• Registration Number: NCT04219995
• Lead Sponsor: Louisiana State University Health Sciences Center in New Orleans

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-01-02
• Study First Submitted QC: 2020-01-03
• Study First Posted: 2020-01-07
• Status Verified: 2020-02
• Study Start: 2020-02-03
• Last Update Submitted: 2020-02-05
• Last Update Posted: 2020-02-07
• Primary Completion: 2021-02
• Study Completion: 2021-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Patients age 2 -18 years of age

2. 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

3. Family's ability to understand and willingness to sign a written informed consent document for patients under 18.

4. Willingness to complete seizure diary for duration of study

5. Willingness to present to all study visits

Exclusion Criteria

1. Patients with history of the following diagnoses:

   1. Traumatic brain injury
   2. Tuberous sclerosis
   3. Sturge Weber
   4. Cortical dysplasia

2. Patients with known hereditary degenerative diseases as follows:

   1. Adrenoleukodystrophy
   2. Neuronal ceroid lipofuscinosis
   3. Leigh Syndrome
   4. Myoclonic epilepsy with ragged red fibers (MERRF)
   5. Rett Syndrome

3. Patients with the following epilepsy syndromes

   1. Infantile spasms
   2. West Syndrome
   3. Progressive myoclonic epilepsy
   4. Dravet syndrome
   5. Doose syndrome
   6. Ohtahara syndrome
   7. Rasmussen's encephalitis

4. Patients with the following metabolic disorders

   1. Phenylketonuria
   2. Maple syrup urine disease
   3. Organic acidemias
   4. Galactosemia
   5. Peroxismal disorders (e.g. Zellwegers)
   6. Lysosomal disorders
   7. Urea cycle disorders

5. Patients with history of immunodeficiency

6. Patients with the following infections

   1. HIV/AIDS
   2. Active or latent TB
   3. Active or suspected bacterial infection
   4. Active, latent or suspected fungemia
   5. Active or suspected parasitic infection

7. Patients with history of malignancy

8. Patients with history of or active myopathy

9. Patients with degenerative neuromuscular disorders

10. Patients with history of hypersensitivity or allergic reactions to corticosteroids

11. Patients with history of psychosis

12. Patients with diabetes mellitus

13. Pregnancy

14. Any underlying predisposition to gastrointestinal bleeding (peptic ulcer disease, gastritis, colitis)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Interventional start	methylprednisolone sodium succinate	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.
Interventional start	Placebo	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.
Placebo start	Placebo	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.
Placebo start	methylprednisolone sodium succinate	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.

Primary Outcome Measures

Name	Time	Method
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.	The percentage of patients with 50% or more reduction in seizure frequency.

Secondary Outcome Measures

Name	Time	Method
Seizure freedom	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).	The percentage of participants who become seizure free over 1 month
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).	Percentage of participants who reports adverse events and the severity of the adverse events.
Drop out percentage	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).	Percentage of participants who drop out of the study due to adverse events

Trial Locations

Locations (1)

Children's Hospital of New Orleans; 🇺🇸 New Orleans, Louisiana, United States