A Study of Divalproex Sodium in Children With ASD and Epileptiform EEG

• Status: Withdrawn
• Trial end date: 2011-01-28
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• Electroencephalography (EEG) records electric patterns produced by the brain, and can detect conditions such as epilepsy or other l abnormalities that may affect brain function. In EEG studies, electric patterns that resemble epileptic seizures are known as epileptiform pattern. These patterns are associated with an increased risk of seizures, even in people who have not been diagnosed with epilepsy. Epileptiform patterns also appear on the EEGs of some children who have autism spectrum disorders but do not have epilepsy. It is unclear if these discharges are related in any way to the symptoms of autism (behavior, language or intellectual abilities).

• Divalproex sodium (Depakote) is a drug that has been used for many years to treat epilepsy and other brain disorders in children and adults. Researchers are interested determining whether treatment with divalproex sodium can reduce epileptiform patterns in children with autism spectrum disorders, and in doing so study whether this treatment can improve behavior, language or cognition in children with autism spectrum disorders.

Objectives:

• To study the effectiveness of using divalproex sodium to reduce epileptiform EEG discharges in children with autism spectrum disorders.

Eligibility:

• Children between 3 and 10 years of age who have an autism spectrum disorder and show frequent epileptiform discharges on an overnight EEG.

Design:

• This study will last for a total of 9 months, with 6 months of treatment with either divalproex sodium or a placebo followed by 3 months of treatment with divalproex sodium only.

• Potential participants will be screened with a physical examination and medical history, blood samples, and psychological tests, and will spend the night in the NIH Clinical Center to have an overnight EEG. Children with frequent epileptiform abnormalities on the EEG will continue with the study; all others will be considered ineligible.

• Eligible participants will receive either divalproex sodium or a placebo to be taken twice daily for 24 weeks. Neither the investigators nor the participants will know which they are taking.

• Participants will have regular visits (every 2-4 weeks) to monitor for adverse effects and to test for possible behavioral improvement, and will also have overnight EEG testing at 12 and 24 weeks.

• At the end of the 24-week study period, participants will have the option to have an additional 12 weeks of treatment with divalproex sodium.

• A final evaluation (including EEG) will be conducted at the end of the final treatment period.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Mental Health (NIMH)
• Treatments: Valproic Acid

Criteria

• INCLUSION CRITERIA:

1. Have a diagnosis of Autistic Disorder, Asperger's syndrome, or Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS).

2. Are aged 3 to 10 years.

3. Weigh at least 12.5 kg.

4. Only children with frequent epileptiform EEG activity on the overnight EEG at NIH will be randomized to start study drug. Frequent discharges are defined as spikes, spike wave, and sharp waves occurring at greater than 5 events per hour.

EXCLUSION CRITERIA:

1. A diagnosis of epilepsy (past or present) excluding febrile seizures.

2. The presence of a severe epileptiform EEG on the sleep EEG at NIH referred to as electrical status epilepticus in sleep (ESES).

3. Previous treatment with divalproex sodium

1. of greater than 6 months duration

2. within the last 12 months

3. that was associated with significant side effects leading to termination of treatment.

4. Recent (less than two months prior to study entry) initiation of a behavioral therapy program or new psychotropic medication, or the plan to change or start a new therapy.

5. Presence of medical condition, such as carnitine deficiency, urea cycle disorder or other metabolic disorder that would be a contraindication to divalproex sodium usage.

6. Renal, hepatic, pancreatic, or hematologic dysfunction as evidenced by increase above upper limits of normal for BUN/creatinine, or values twice the upper limit of normal for serum transaminases (ALT/SGPT, AST/SGOT), values twice the upper limit of normal for serum lipase and amylase, platelets < 80,000 /mcL, WBC< 3.0 10(3)/mcL.

7. Pregnancy

8. Concomitant use of medication contraindicated with divalproex sodium including topiramate, lamotragine, and drugs that inhibit cytochrome p450 enzymes.

9. Behavioral management issues (e.g. self-injury, aggressiveness) that are severe enough to be of safety concerns (to subject and/or staff).

10. Absence of primary care physician.