Developmental Effects On Children Of Women Who Take Antiepileptic Drugs During Pregnancy - Full Text View

Sponsor:	Emory University
Collaborator:	National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by:	Emory University
ClinicalTrials.gov Identifier:	NCT00021866

Purpose

The purpose of this study is to determine if antiepileptic drugs (AEDs) differ in their neurodevelopmental effects. Specifically, do the children of the women with epilepsy differ in their behavioral and cognitive development depending on which AED their mother takes during pregnancy?

Condition	Intervention
Epilepsy Seizure Cognition Disorders	Behavioral: Differential Abilities Scale Behavioral: Neuropsychological Testing

Study Type:	Observational
Study Design:	Observational Model: Family-Based Time Perspective: Prospective
Official Title:	Neurodevelopmental Effects of Antiepileptic Drugs II: the NEAD Study

Resource links provided by NLM:

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

MedlinePlus related topics: Epilepsy Memory Seizures

Drug Information available for: Phenytoin Divalproex sodium Lamotrigine Valproic acid Carbamazepine Phenytoin sodium Valproate Sodium

U.S. FDA Resources

Further study details as provided by Emory University:

Primary Outcome Measures:

Child IQ as measured by the Differential Abilities Scale at 6 Years of age [ Time Frame: 6 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Executive Functioning,Tower-NEPSY [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
Linguistic Functioning via Expressive one word vocabulary test and NEPSY subscales [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
Visual-Spatial Motor Functioning via NEPSY subscale and Visual-Motor Integration Scale [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
Memory via Children's Memory Scale [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
Motor Functioning via Grooved Pegboard [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
Academic Functioning via Wide Range Achievement Test [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
Adaptive Functioning via Adaptive Behavior System -2nd Edition [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
Behavior via Behavior Assessment for Children & Parent Stress Index [ Time Frame: 6 Years ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

Venous blood for AED levels Cord Blood for G6PD, Homocysteine Saliva for drug metabolizing enzymes, antioxidant enzymes, DNA repair enzymes, drug membrane transporter proteins and folate-related genes

Enrollment:	331
Study Start Date:	September 2000
Estimated Study Completion Date:	August 2011
Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Carbamazepine Children and their mothers exposed to Carbamazepine monotherapy in utero	Behavioral: Differential Abilities Scale IQ measurement at 3, 4.5 and 6 years of age Other Name: DAS Behavioral: Neuropsychological Testing Tests of memory, attention, and behavior administered at 2,3, 4.5 and 6 Years of age Other Names: (Toni-3) Test of Nonverbal Intelligence (WAIS) - Wechslers Adult Intelligence Scale -revised Beck Depression Inventory Bayley Scales of Infant Development, NEPSY Trails Preschool Preschool Language Scale-4 Expressive One-Word Vocabulary TEst Peabody Picture Vocabulary Test Developmental Test of Visual-Motor Integration Children's Memory Scale Grooved Pegboard Bracken Basic Concepts Scale Wide Range Achievement TEst Adaptive Behavior Assessment Scale Behavioral Assessment for Children Parenting Stress Index
Phenytoin Children and their mothers exposed to phenytoin in utero	Behavioral: Differential Abilities Scale IQ measurement at 3, 4.5 and 6 years of age Other Name: DAS Behavioral: Neuropsychological Testing Tests of memory, attention, and behavior administered at 2,3, 4.5 and 6 Years of age Other Names: (Toni-3) Test of Nonverbal Intelligence (WAIS) - Wechslers Adult Intelligence Scale -revised Beck Depression Inventory Bayley Scales of Infant Development, NEPSY Trails Preschool Preschool Language Scale-4 Expressive One-Word Vocabulary TEst Peabody Picture Vocabulary Test Developmental Test of Visual-Motor Integration Children's Memory Scale Grooved Pegboard Bracken Basic Concepts Scale Wide Range Achievement TEst Adaptive Behavior Assessment Scale Behavioral Assessment for Children Parenting Stress Index
Lamotrigine Children and their mothers exposed to Lamotrigine in utero	Behavioral: Differential Abilities Scale IQ measurement at 3, 4.5 and 6 years of age Other Name: DAS Behavioral: Neuropsychological Testing Tests of memory, attention, and behavior administered at 2,3, 4.5 and 6 Years of age Other Names: (Toni-3) Test of Nonverbal Intelligence (WAIS) - Wechslers Adult Intelligence Scale -revised Beck Depression Inventory Bayley Scales of Infant Development, NEPSY Trails Preschool Preschool Language Scale-4 Expressive One-Word Vocabulary TEst Peabody Picture Vocabulary Test Developmental Test of Visual-Motor Integration Children's Memory Scale Grooved Pegboard Bracken Basic Concepts Scale Wide Range Achievement TEst Adaptive Behavior Assessment Scale Behavioral Assessment for Children Parenting Stress Index
Valproate Children and their mothers exposed to Valproate in utero	Behavioral: Differential Abilities Scale IQ measurement at 3, 4.5 and 6 years of age Other Name: DAS Behavioral: Neuropsychological Testing Tests of memory, attention, and behavior administered at 2,3, 4.5 and 6 Years of age Other Names: (Toni-3) Test of Nonverbal Intelligence (WAIS) - Wechslers Adult Intelligence Scale -revised Beck Depression Inventory Bayley Scales of Infant Development, NEPSY Trails Preschool Preschool Language Scale-4 Expressive One-Word Vocabulary TEst Peabody Picture Vocabulary Test Developmental Test of Visual-Motor Integration Children's Memory Scale Grooved Pegboard Bracken Basic Concepts Scale Wide Range Achievement TEst Adaptive Behavior Assessment Scale Behavioral Assessment for Children Parenting Stress Index

Detailed Description:

This is a prospective investigation enrolling 285 to 380 women with epilepsy during the first two trimesters of their pregnancies. There are 25 clinical centers as well as the database center. The women will be taking one of the following AEDs: carbamazepine, phenytoin, valproate, or lamotrigine. Cognitive and behavioral testing of the child will be done up to the age of 6 years. The study does not change the woman's doctor and does not interfere with the care of the treating physician.

Eligibility

Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Mothers and their child(ren) who were exposed to one of the following monotherapies in utero- Lamotrigine, Carbamazepine, Phenytoin, or Valproate. Fathers of the children and a first degree materal relative of the mother are also invited to have IQ testing and medical history

Criteria

Subject must be diagnosed with partial seizures and/or secondary generalization or primary generalized seizures (absence, atonic, myoclonic, and generalized tonic-clonic seizures)
Subjects must be on either carbamazepine, lamotrigine, phenytoin, or valproate monotherapy.
Mothers must not have a history of drug abuse (including alcohol) in the last year and have no sequelae of drug abuse.
Mothers must be able to maintain an accurate seizure diary of major motor seizures
Subjects must have an IQ greater than or equal to 70 points.
Subjects must have a history of a negative RPR and HIV.
Subjects must not have progressive cerebral disease or presence of other major medical illness
Subjects must not have exposure to known teratogens during pregnancy, except AEDs.
Subjects must not have poor compliance with prenatal care.
Subjects must have adequate reading skills to perform the cognitive tests.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00021866

Show 21 Study Locations

Sponsors and Collaborators

Emory University

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Principal Investigator:

Kimford J. Meador, M.D.

Emory University, Atlanta

More Information

Additional Information:

Click here for more information about this study and a list of recruiting centers This link exits the ClinicalTrials.gov site

Publications:

Meador KJ, Chadwick D, Clayton-Smith J, Pennell P, Liporace J, Kalayian L, and NEAD Study Group. Antiepileptic drugs in pregnancy: Differences in U.K. and U.S.A. Epilepsia, 2003;44 (Suppl. 9):289.

Meador KJ, Page P, Liporace J, Kalayjian L, NEAD Study Group. Antiepileptic Drugs in Pregnancy. Neurology 2004;62 (Suppl 5):A311.

Meador KJ, Baker GA, Clayton Smith J, Pennell P, Liporace J, Kalayjian L, Kini U, NEAD Study Group. Differential Effects of Antiepileptic Drugs on Serious Adverse Outcomes in Children Exposed In Utero. Epilepsia 2004;45 (Suppl 3):58

Meador KM, Loring DW, Baker G, Smith JC, Pennell P, Liporace J, Kalayjian L, Kini U, NEAD Study Group. Differential and dose dependent effects of in utero antiepileptic drugs. Neurology 2005;64 (Suppl 1):A427

Meador KJ, Baker GA, Finnell RH, Kalayjian LA, Liporace JD, Loring DW, Mawer G, Pennell PB, Smith JC, Wolff MC; NEAD Study Group. In utero antiepileptic drug exposure: fetal death and malformations. Neurology. 2006 Aug 8;67(3):407-12.

Responsible Party:	Kimford J. Meador, M.D., Emory University
ClinicalTrials.gov Identifier:	NCT00021866 History of Changes
Other Study ID Numbers:	R01NS038455, 2RO1NS38455
Study First Received:	August 8, 2001
Last Updated:	June 23, 2011
Health Authority:	United States: Federal Government

Keywords provided by Emory University:

epilepsy
seizure
pregnancy
antiepileptic
AED
carbamazepine

phenytoin
valproate
lamotrigine
child
behavior

Additional relevant MeSH terms:

Cognition Disorders
Epilepsy
Seizures
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Lamotrigine
Anticonvulsants
Phenytoin
Valproic Acid
Carbamazepine

Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents

ClinicalTrials.gov processed this record on February 12, 2012