AutismPhase 2NCT02094651
Treatment of Children With Autism Spectrum Disorders and Epileptiform EEG With Divalproex Sodium
A Phase 2 study testing divalproex sodium in people with Autism, run by Boston Children's Hospital at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 4 to 10 years
- Conditions the study is for
- Autism
- What is being tested?
- divalproex sodium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2014to Oct 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Boston Childrens Hospital
Boston, Massachusetts, 02115
University of Louisville
Louisville, Kentucky, 40202
About this study
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).
Read the detailed description
Epilepsy and epileptiform EEG abnormalities are common co-morbidities in Autism Spectrum Disorders (ASD) that can be considered important biomarkers of cortical dysfunction in these disorders. They may represent a measure of the excitatory-inhibitory imbalance posited to be involved in the pathogenesis of the disorder. Treatment of epilepsy is always indicated, but treatment of isolated epileptiform EEG (i.e. in the absence of clinical seizures) is frankly controversial. Since data suggest that these epileptiform discharges are associated with deficits in attention, language and behavior, the investigators believe that they may represent an important and novel treatment target in this population. The proposed study brings together a group of investigators long interested in this problem in order to investigate the efficacy of using an anticonvulsant medication with spike suppression capabilities (VPA in the form of divalproex sodium) to treat children with ASD and isolated epileptiform EEGs. Recruiting from 3 large autism centers (Boston Children's Hospital (BCH) and Vanderbilt University (VU) and University of Louisville (U of L)) with very large pediatric epilepsy units, the investigators propose a 26 week randomized placebo controlled cross over study of VPA in 4-8 year old children with ASD with frequent epileptiform EEG discharges.
- Conditions
- Autism
- Being tested
- divalproex sodium, Placebo
- Keywords
- Abnormal EEGs
- Medical subject headings
- Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
divalproex sodiumDrug
Also called Depakote, valproic acid, VPA, sodium valproate
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.
PlaceboOther
The placebo is an inactive substance that looks like the active drug.
| Study group | Role | What they receive |
|---|---|---|
| divalproex sodium | Experimental | divalproex sodium will be administered in sprinkle capsule formulation, target dose of 30mg/kg, drug will be administered for 12 weeks Receives: 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 Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: In this crossover study participants will be on drug and placebo for 12 weeks each
Secondary outcomes (1)
behavior changes in drug vs placebo.
To determine if administration of VPA results in improvement in behavior compared to placebo. Based on preliminary data the investigators hypothesize that VPA will be significantly associated with improvement in the areas of aggression, attention and externalizing behaviors as measured by the Child Behavior Checklist (CBCL), the primary behavioral outcome variables. A wide range of other behavioral measures (secondary outcomes) including those related to core ASD symptoms, language, adaptive functioning, sensory and motor behaviors to identify will also be examined. Behavioral measures will be examined in relation to reduction of epileptiform discharges. The investigators will also include both objective and subjective measures of sleep and examine the effect of sleep changes in relation to EEG discharge profiles and behavior.
Measured: In this crossover study participants will be on drug and placebo for 12 weeks each
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2014 (estimated)
- Study startApr 2014
- Primary completionOct 2016
- Study completionOct 2016
Why it stopped: No eligible patients were enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AutismStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Louisville
- Responsible party
- Principal investigator, Sarah Spence, Boston Children's Hospital
- Investigators
- Sarah Spence, MD PhD, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02094651
- Sponsor's protocol ID
- P00005744
- Status last verified
- Oct 2016
- First submitted
- 10 Mar 2014
- Last updated
- 21 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Children With Autism Spectrum Disorders and Epileptiform EEG With Divalproex Sodium
- ClinicalTrials.gov ID
- NCT02094651
- Acronym / sponsor ID
- P00005744
- Conditions
- Autism
- Keywords
- Abnormal EEGs
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No eligible patients were enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- University of Louisville
- Study start
- Apr 2014
- Primary completion
- Oct 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 24 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Epilepsy and epileptiform EEG abnormalities are common co-morbidities in Autism Spectrum Disorders (ASD) that can be considered important biomarkers of cortical dysfunction in these disorders. They may represent a measure of the excitatory-inhibitory imbalance posited to be involved in the pathogenesis of the disorder. Treatment of epilepsy is always indicated, but treatment of isolated epileptiform EEG (i.e. in the absence of clinical seizures) is frankly controversial. Since data suggest that these epileptiform discharges are associated with deficits in attention, language and behavior, the investigators believe that they may represent an important and novel treatment target in this population. The proposed study brings together a group of investigators long interested in this problem in order to investigate the efficacy of using an anticonvulsant medication with spike suppression capabilities (VPA in the form of divalproex sodium) to treat children with ASD and isolated epileptiform EEGs. Recruiting from 3 large autism centers (Boston Children's Hospital (BCH) and Vanderbilt University (VU) and University of Louisville (U of L)) with very large pediatric epilepsy units, the investigators propose a 26 week randomized placebo controlled cross over study of VPA in 4-8 year old children with ASD with frequent epileptiform EEG discharges.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| divalproex sodium | Experimental | Drug: divalproex sodiumdivalproex sodium will be administered in sprinkle capsule formulation, target dose of 30mg/kg, drug will be administered for 12 weeks |
| Placebo | Placebo comparator | Other: PlaceboBlue and white capsules with equivalent amount of lactose spheres/beads inside Placebo will be formulated to look identical to the active medication |
Who may qualify
- Ages
- 4 to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (14 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| divalproex sodiumAlso: Depakote, valproic acid, VPA, sodium valproateThe 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. | Drug | divalproex sodium |
| PlaceboThe placebo is an inactive substance that looks like the active drug. | Other | Placebo |
Primary outcome
effect of drug vs placebo on reduction in epileptiform EEG discharges in children with ASD
Time frame: In this crossover study participants will be on drug and placebo for 12 weeks each
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.
1 secondary outcome
behavior changes in drug vs placebo.
Time frame: In this crossover study participants will be on drug and placebo for 12 weeks each
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2016.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sarah Spence, MD PhD principal investigator
Boston Children's Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing divalproex sodium in people with Autism, run by Boston Children's Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 21 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
effect of drug vs placebo on reduction in epileptiform EEG discharges in children with ASD (time frame: In this crossover study participants will be on drug and placebo for 12 weeks each). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2016; AzTrials last refreshed its copy on 8 Nov 2026.