Phase II Randomized Study of Early Surgery Vs Multiple Sequential Antiepileptic Drug Therapy for Infantile Spasms Refractory to Standard Treatment

Sponsor

National Center for Research Resources (NCRR) (NIH)

Overall Status

Completed

CT.gov ID

NCT00004758

Collaborator

National Institute of Neurological Disorders and Stroke (NINDS) (NIH), University of California, Los Angeles (Other)

Enrollment

Study Details

Study Description

Brief Summary

OBJECTIVES: I. Evaluate the efficacy of surgical resection of an identifiable zone of cortical abnormality versus multiple drug therapy in children with infantile spasms refractory to standard therapy.

Assess how infantile spasms interfere with development and whether this is partially reversible.
Determine the predictors of good surgical outcome and whether surgery permanently controls seizures and improves development.

Condition or Disease	Intervention/Treatment	Phase
Spasms, Infantile Epilepsy	Drug: carbamazepine Drug: corticotropin Drug: nitrazepam Drug: pyridoxine Drug: valproic acid Procedure: Surgery	Phase 2

Detailed Description

PROTOCOL OUTLINE: This is a randomized study. Patients are randomly assigned to 1 of 2 treatment groups. The first group undergoes sequential antiepileptic therapy with pyridoxine, corticotropin, valproic acid, carbamazepine, and nitrazepam. The sequence of administration may be altered based on drugs taken prior to entry. Any drug may be omitted due to medical contraindications or prior use at study doses or higher.

The second group undergoes surgical resection of the zone of cortical abnormality. A functional hemispherectomy is performed for hemiparesis or diffuse unihemispheric dysfunction.

If seizures are controlled in the first group at 3 months, the current medication is maintained; if seizures are not controlled, sequential therapy continues to completion. Patients experiencing uncontrolled seizures at 6 months cross to surgery.

Surgical patients experiencing uncontrolled seizures at 3 months or persistent seizures after taper of pre-study antiepileptics cross to drug therapy.

All patients are followed at 6 months and 1, 2, 3, 5, 7, and 10 years.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Primary Purpose:

Treatment

Study Start Date :

Nov 1, 1993

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Years to 2 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

PROTOCOL ENTRY CRITERIA:

Disease Characteristics

Infantile spasms or seizures with diagnosis based on the following: short muscular contractions leading to flexion or extension; Single or repetitive electroencephalogram (EEG) consistent with diagnosis, i.e., hypsarrhythmia, modified hypsarrhythmia, multifocal spike and wave abnormalities; developmental quotient less than 70
Zone of cortical abnormality in 1 lobe, contiguous multilobes, or 1 hemisphere; confirmed by historical, neurological, and physical evidence, including EEG, closed circuit televised EEG, computed tomography, magnetic resonance imaging, and/or positron-emission tomography; at least 2 abnormal test/imaging results required
No treatable seizure etiology such as metabolic disease or infection

Prior/Concurrent Therapy

Failed standard therapy, i.e., refractory to corticotropin (at least 40 IU/day for 14 days) as follows: persistent infantile spasms OR recurrent spasms after discontinuation or taper OR complications requiring dose modification
At least 1 month of standard antiepileptic drug with documented therapeutic blood levels

Patient Characteristics