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

• ClinicalTrials.gov Identifier: NCT00004758
• Recruitment Status: Completed
• First Posted: February 25, 2000
• Last Update Posted: June 24, 2005
• Sponsor: National Center for Research Resources (NCRR)
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); University of California, Los Angeles
• Information provided by: Office of Rare Diseases (ORD)

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.

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.

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 (Clinical Trial)
• Enrollment: 30 participants
• Allocation: Randomized
• Primary Purpose: Treatment
• Study Start Date: November 1993

Arms and Interventions

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: up to 2 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Sponsors and Collaborators

National Center for Research Resources (NCRR)

National Institute of Neurological Disorders and Stroke (NINDS)

University of California, Los Angeles

Investigators

• Study Chair: W. Donald Shields; University of California, Los Angeles

More Information

• ClinicalTrials.gov Identifier: NCT00004758 History of Changes
• Other Study ID Numbers: 199/11691; UCLA-9508342
• First Posted: February 25, 2000
• Last Update Posted: June 24, 2005
• Last Verified: December 2001

Keywords provided by Office of Rare Diseases (ORD):

infantile spasms; epilepsy; neurologic and psychiatric disorders; rare disease; seizures

Additional relevant MeSH terms:

Carbamazepine; Psychotropic Drugs; Epilepsy; Spasm; Spasms, Infantile; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Epilepsy, Generalized; Epileptic Syndromes; Pyridoxine; Valproic Acid; Nitrazepam; Adrenocorticotropic Hormone; Anticonvulsants; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; GABA Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Antimanic Agents; Tranquilizing Agents; Central Nervous System Depressants; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents