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

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.

II. Assess how infantile spasms interfere with development and whether this is partially reversible.

III. Determine the predictors of good surgical outcome and whether surgery permanently controls seizures and improves development.

Study Overview

• Status: Completed
• Conditions: Epilepsy; Spasms, Infantile
• Intervention / Treatment: Procedure: Surgery; Drug: valproic acid; Drug: pyridoxine; Drug: carbamazepine; Drug: corticotropin; Drug: nitrazepam

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 Type: Interventional
• Enrollment: 30
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

• No medical contraindication to surgery
• English-speaking family

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: National Center for Research Resources (NCRR)
• Collaborators: University of California, Los Angeles; National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Study Chair: W. Donald Shields, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start: November 1, 1993

Study Registration Dates

• First Submitted: February 24, 2000
• First Submitted That Met QC Criteria: February 24, 2000
• First Posted (Estimate): February 25, 2000

Study Record Updates

• Last Update Posted (Estimate): June 24, 2005
• Last Update Submitted That Met QC Criteria: June 23, 2005
• Last Verified: December 1, 2001

More Information

Terms related to this study

• Keywords: epilepsy; neurologic and psychiatric disorders; rare disease; seizures; infantile spasms
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Neurologic Manifestations; Neuromuscular Manifestations; Epilepsy; Spasms, Infantile; Spasm; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Micronutrients; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anticonvulsants; Sodium Channel Blockers; Antimanic Agents; Cytochrome P-450 Enzyme Inducers; Vitamins; Cytochrome P-450 CYP3A Inducers; Vitamin B Complex; Valproic Acid; Carbamazepine; Pyridoxine; Adrenocorticotropic Hormone; Nitrazepam
• Other Study ID Numbers: 199/11691; UCLA-9508342