Treatment of Children With Autism Spectrum Disorders and Epileptiform EEG With Divalproex Sodium

NCT02094651 | Withdrawn Phase 2 DMC

• 1 other identifier: P00005744
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine if treatment of epileptiform abnormalities in children with autism spectrum disorder will improve any behaviors in these children. The investigators will study a number of different behavioral outcomes including behaviors related to attention, social communication, repetitive behaviors, maladaptive behaviors, language, motor and sensory, and sleep. The investigators will use an anticonvulsant medication called valproic acid (in the form of sodium divalproex).

Conditions

Autism

Keywords

Abnormal EEGs

Outcome Measures

Primary Outcomes (1)

• effect of drug vs placebo on reduction in epileptiform EEG discharges in children with ASD

  To examine the effect of divalproex sodium (valproate or VPA) on epileptiform EEG discharges in children with ASD. The investigators hypothesize that VPA will significantly reduce discharge counts (primary outcome measure) compared to placebo.

  In this crossover study participants will be on drug and placebo for 12 weeks each

Secondary Outcomes (1)

• behavior changes in drug vs placebo.

  In this crossover study participants will be on drug and placebo for 12 weeks each

Study Arms (2)

divalproex sodium

EXPERIMENTAL

divalproex sodium will be administered in sprinkle capsule formulation, target dose of 30mg/kg, drug will be administered for 12 weeks

Drug: divalproex sodium

Placebo

PLACEBO COMPARATOR

Blue and white capsules with equivalent amount of lactose spheres/beads inside Placebo will be formulated to look identical to the active medication

Other: Placebo

Interventions

divalproex sodium DRUG

The drug is an FDA approved medication for seizures but has not been approved for the treatment of epileptiform EEG abnormalities in the absence of clinical seizures.

Also known as: Depakote, valproic acid, VPA, sodium valproate

divalproex sodium

Placebo OTHER

The placebo is an inactive substance that looks like the active drug.

Placebo

Eligibility Criteria

• Age: 4 Years - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female patients aged 4 to 10 years.
• Diagnosis of with ASD (Autistic Disorder, Asperger's Disorder, or pervasive developmental disorder (PDD-NOS).
• Frequent epileptiform discharges on EEG (defined as spikes, spike wave, and sharp waves occurring at greater than 15 events per hour).
• Intelligence quotient (IQ) range 40 to 100.
• Weight \> or = 12.5 kg.
• English speaking families

You may not qualify if:

• History of epilepsy, known neurogenetic disorder or chromosomal abnormalities with high rates of epilepsy (15q duplication syndrome, 16p deletion/duplication syndrome, Fragile X, tuberous sclerosis complex), or structural brain lesion (prior stroke, migrational defects, brain malformations).
• The presence of a severe epileptiform EEG on the sleep EEG referred to as electrical status epilepticus in sleep (ESES) in sleep
• Previous treatment with divalproex sodium that is any one of the following:
• of greater than 6 months duration
• within the last 12 months
• that was associated with significant side effects leading to termination of treatment
• Children who have had general anesthesia within the six months or sedation within 2 weeks of study enrollment.
• 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.
• Presence of a significant untreated medical problem (obstructive sleep apnea, restless legs syndrome, GERD, etc.) which may have significant impact on sleep study measures.
• Renal, hepatic, pancreatic, or hematologic dysfunction as evidenced by values 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\<3.0 103 /mcL.
• Concomitant use of medication contraindicated with divalproex sodium including topiramate, lamotrigine, and drugs that inhibit cytochrome p450 enzymes.
• Behavioral management issues (e.g. self-injury, aggressiveness) severe enough to be of safety concerns (to subject and/or staff).
• Absence of primary care physician.

Sponsors & Collaborators

• Boston Children's Hospital: lead
• University of Louisville: collaborator

Study Sites (2)

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Boston Childrens Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Autistic Disorder

Interventions

Valproic Acid

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; 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 Officials

• Sarah Spence, MD PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant in Neurology

Study Record Dates

• First Submitted: March 10, 2014
• First Posted: March 24, 2014
• Study Start: April 1, 2014
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: October 21, 2016

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)