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

NCT01170325 | Withdrawn Phase 2

• 2 other identifiers: 10015710-M-0157
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Autism; Autism Spectrum Disorders

Keywords

Valproic Acid; Divalproex; Autism; EEG; Electroencephalogram (EEG); Depakote

Outcome Measures

Primary Outcomes (1)

• epileptiform EEG discharges

  24 weeks

Secondary Outcomes (1)

• Improvement in behavior

Study Arms (2)

Group A

EXPERIMENTAL

Drug: Divalproex Sodium

Group B

PLACEBO COMPARATOR

Drug: Placebo Comparator

Interventions

Divalproex Sodium DRUG

Group A

Placebo Comparator DRUG

Group B

Eligibility Criteria

• Age: 3 Years - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Have a diagnosis of Autistic Disorder, Asperger's syndrome, or Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS).
• Are aged 3 to 10 years.
• Weigh at least 12.5 kg.
• 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.

You may not qualify if:

• A diagnosis of epilepsy (past or present) excluding febrile seizures.
• The presence of a severe epileptiform EEG on the sleep EEG at NIH referred to as electrical status epilepticus in sleep (ESES).
• Previous treatment with divalproex sodium
• of greater than 6 months duration
• within the last 12 months
• that was associated with significant side effects leading to termination of treatment.
• 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.
• Presence of medical condition, such as carnitine deficiency, urea cycle disorder or other metabolic disorder that would be a contraindication to divalproex sodium usage.
• 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.
• Pregnancy
• Concomitant use of medication contraindicated with divalproex sodium including topiramate, lamotragine, and drugs that inhibit cytochrome p450 enzymes.
• Behavioral management issues (e.g. self-injury, aggressiveness) that are severe enough to be of safety concerns (to subject and/or staff).
• Absence of primary care physician.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Aarts JH, Binnie CD, Smit AM, Wilkins AJ. Selective cognitive impairment during focal and generalized epileptiform EEG activity. Brain. 1984 Mar;107 ( Pt 1):293-308. doi: 10.1093/brain/107.1.293.

  PMID: 6421454 BACKGROUND

• Artama M, Isojarvi JI, Auvinen A. Antiepileptic drug use and birth rate in patients with epilepsy--a population-based cohort study in Finland. Hum Reprod. 2006 Sep;21(9):2290-5. doi: 10.1093/humrep/del194. Epub 2006 Jun 3.

  PMID: 16751648 BACKGROUND

• Binnie CD. Cognitive impairment during epileptiform discharges: is it ever justifiable to treat the EEG? Lancet Neurol. 2003 Dec;2(12):725-30. doi: 10.1016/s1474-4422(03)00584-2.

  PMID: 14636777 BACKGROUND

MeSH Terms

Conditions

Autistic Disorder; Autism Spectrum Disorder

Interventions

Valproic Acid

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: July 24, 2010
• First Posted: July 27, 2010
• Study Start: June 30, 2010
• Primary Completion: January 28, 2011
• Study Completion: January 28, 2011
• Last Updated: July 2, 2017

Record last verified: 2011-01-28

Locations

US (1)