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

Sponsors and Collaborators:	National Center for Research Resources (NCRR) National Institute of Neurological Disorders and Stroke (NINDS) University of California, Los Angeles
Information provided by:	Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:	NCT00004758

Purpose

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	Intervention	Phase
Spasms, Infantile Epilepsy	Drug: carbamazepine Drug: corticotropin Drug: nitrazepam Drug: pyridoxine Drug: valproic acid Procedure: Surgery	Phase II

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy pyridoxine-dependent epilepsy

MedlinePlus related topics: Epilepsy Seizures

Drug Information available for: Vitamin B 6 5-Hydroxy-6-methyl-3,4-pyridinedimethanol hydrochloride Pyridoxine Divalproex sodium Valproate Sodium Valproic acid Corticotropin Carbamazepine Nitrazepam

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized

Further study details as provided by Office of Rare Diseases (ORD):

Estimated Enrollment:	30
Study Start Date:	November 1993

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.

Eligibility

Ages Eligible for Study:	up to 2 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004758

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

Study ID Numbers:	199/11691, UCLA-9508342
Study First Received:	February 24, 2000
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00004758
Health Authority:	United States: Federal Government

Keywords provided by Office of Rare Diseases (ORD):

infantile spasms
epilepsy
neurologic and psychiatric disorders
rare disease
seizures

Study placed in the following topic categories:

Spasm
Spasms, Infantile
West syndrome
Nitrazepam
Seizures
Rare Diseases
Central Nervous System Diseases
Brain Diseases
Valproic Acid
Adrenocorticotropic Hormone

Vitamin B 6
Signs and Symptoms
Carbamazepine
Epilepsy
Mental Disorders
Neurologic Manifestations
Pyridoxine
Infantile spasms
Epilepsy, Generalized

Additional relevant MeSH terms:

Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
GABA Modulators
Physiological Effects of Drugs
Psychotropic Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Hormones
Sensory System Agents
Vitamins
Therapeutic Uses
Hypnotics and Sedatives
Micronutrients
Analgesics
Neuromuscular Manifestations

Tranquilizing Agents
Vitamin B Complex
Growth Substances
Nervous System Diseases
Central Nervous System Depressants
Enzyme Inhibitors
Antimanic Agents
Pharmacologic Actions
Analgesics, Non-Narcotic
GABA Agents
Anti-Anxiety Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on January 16, 2009