AutismPhase 2NCT01170325
A Study of Divalproex Sodium in Children With ASD and Epileptiform EEG
A Phase 2 study testing Divalproex Sodium in people with Autism and Autism Spectrum Disorders, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 10 years
- Conditions the study is for
- Autism, Autism Spectrum Disorders
- What is being tested?
- Divalproex Sodium
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jun 2010to 28 Jan 2011
- 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 3 to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Study of Divalproex Sodium in Children With Autism Spectrum Disorder and Epileptiform EEG
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.
Read more
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.
Read the detailed description
Objective
The objective of this study is to investigate the efficacy of divalproex sodium in reduction of epileptiform EEG discharges in children with Autism Spectrum Disorders (ASD). ASDs are neurodevelopmental disorders that result in abnormalities of social and language development and are associated with rigid and repetitive behaviors. ASD prevalence may be as common as 1 in 110 and as many as 1/3 of these individuals have seizures. Abnormal electroencephalograms (EEGs) (without seizure activity) are even more prevalent (Spence \& Schneider, 2009). In an ongoing study at the NIMH, approximately 50% of children without epilepsy had epileptiform discharges present on overnight EEG. The relationship between this abnormal activity and autism symptoms has not yet been studied; however, data from other epilepsy syndromes suggest that these epileptiform discharges contribute to behavioral and cognitive deficits. It is also unknown whether or not reduction of the epileptiform discharges will result in improved behavior and more rapid intellectual and social development in children with ASD. This pilot study is designed to address that question.
Study Population
100 children with ASDs including Autistic Disorder, Asperger's or PDD-NOS ages 3-10 will be screened to find up to 40 children with frequent epileptiform discharges noted on overnight EEG. Allowing for up to 20% drop out, we expect at least 32 to complete the study.
Design
The proposed investigation is a 9 month long trial with a 6 month double-blind placebo controlled trial of divalproex sodium (Depakote) and a 3 month open label extension phase. Prior to study entry, potential subjects will be evaluated with the standard PDN diagnostic/behavioral assessment (06-M-0065). Children meeting eligibility criteria will undergo an overnight EEG and those with frequent epileptiform discharges will be randomly assigned to receive divalproex sodium or placebo. Study drugs will be administered in a blinded fashion for 24 weeks with overnight EEG at 12 and 24 weeks. Biweekly then monthly visits with laboratory studies will monitor for behavioral improvement and for potential adverse effects. A 3 month open label extension phase follows.
Outcome Measures
The primary outcome measure will be EEG changes; tolerability and changes in behavioral symptoms will be exploratory secondary outcome assessments. It is hypothesized that divalproex will be superior to placebo in reducing epileptiform discharges on the EEG. In addition, exploratory analyses will investigate whether children who demonstrate improvements and even normalization of the EEG pattern will have more associated behavioral improvements than those for whom the EEG does not improve.
- Conditions
- Autism, Autism Spectrum Disorders
- Being tested
- Divalproex Sodium, Placebo Comparator
- Keywords
- Valproic Acid, Divalproex, Autism, EEG, Electroencephalogram (EEG), Depakote
- Medical subject headings
- Autistic Disorder, Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Divalproex SodiumDrug
Placebo ComparatorDrug
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Not described Receives: Drug: Divalproex Sodium |
| Group B | Placebo comparator | Not described Receives: Drug: Placebo Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
epileptiform EEG discharges
Measured: 24 weeks
Secondary outcomes (1)
Improvement in behavior
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2010 (estimated)
- Study start30 Jun 2010
- Primary completion28 Jan 2011
- Study completion28 Jan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for AutismStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The 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
- Parallel groups
- Masking
- Double blind
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01170325
- Sponsor's protocol ID
- 100157
- Other IDs
- 10-M-0157
- Status last verified
- 28 Jan 2011
- First submitted
- 24 Jul 2010
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
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.
PubMed 6421454Artama 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.
PubMed 16751648Binnie 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.
PubMed 14636777
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Divalproex Sodium in Children With Autism Spectrum Disorder and Epileptiform EEG
- ClinicalTrials.gov ID
- NCT01170325
- Acronym / sponsor ID
- 100157
- Conditions
- Autism, Autism Spectrum Disorders
- Keywords
- Valproic Acid, Divalproex, Autism, EEG, Electroencephalogram (EEG), Depakote
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 30 Jun 2010
- Primary completion
- 28 Jan 2011 (actual)
- Study completion
- 28 Jan 2011 (actual)
- First posted
- 27 Jul 2010 (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.
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.
Detailed description
Objective
The objective of this study is to investigate the efficacy of divalproex sodium in reduction of epileptiform EEG discharges in children with Autism Spectrum Disorders (ASD). ASDs are neurodevelopmental disorders that result in abnormalities of social and language development and are associated with rigid and repetitive behaviors. ASD prevalence may be as common as 1 in 110 and as many as 1/3 of these individuals have seizures. Abnormal electroencephalograms (EEGs) (without seizure activity) are even more prevalent (Spence \& Schneider, 2009). In an ongoing study at the NIMH, approximately 50% of children without epilepsy had epileptiform discharges present on overnight EEG. The relationship between this abnormal activity and autism symptoms has not yet been studied; however, data from other epilepsy syndromes suggest that these epileptiform discharges contribute to behavioral and cognitive deficits. It is also unknown whether or not reduction of the epileptiform discharges will result in improved behavior and more rapid intellectual and social development in children with ASD. This pilot study is designed to address that question.
Study Population
100 children with ASDs including Autistic Disorder, Asperger's or PDD-NOS ages 3-10 will be screened to find up to 40 children with frequent epileptiform discharges noted on overnight EEG. Allowing for up to 20% drop out, we expect at least 32 to complete the study.
Design
The proposed investigation is a 9 month long trial with a 6 month double-blind placebo controlled trial of divalproex sodium (Depakote) and a 3 month open label extension phase. Prior to study entry, potential subjects will be evaluated with the standard PDN diagnostic/behavioral assessment (06-M-0065). Children meeting eligibility criteria will undergo an overnight EEG and those with frequent epileptiform discharges will be randomly assigned to receive divalproex sodium or placebo. Study drugs will be administered in a blinded fashion for 24 weeks with overnight EEG at 12 and 24 weeks. Biweekly then monthly visits with laboratory studies will monitor for behavioral improvement and for potential adverse effects. A 3 month open label extension phase follows.
Outcome Measures
The primary outcome measure will be EEG changes; tolerability and changes in behavioral symptoms will be exploratory secondary outcome assessments. It is hypothesized that divalproex will be superior to placebo in reducing epileptiform discharges on the EEG. In addition, exploratory analyses will investigate whether children who demonstrate improvements and even normalization of the EEG pattern will have more associated behavioral improvements than those for whom the EEG does not improve.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: Divalproex Sodium |
| Group B | Placebo comparator | Drug: Placebo Comparator |
Who may qualify
- Ages
- 3 to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
Key exclusion criteria (13 listed)
- 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
- 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.
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 Sodium | Drug | Group A |
| Placebo Comparator | Drug | Group B |
Primary outcome
epileptiform EEG discharges
Time frame: 24 weeks
1 secondary outcome
Improvement in behavior
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 2 Jul 2017.
- Background: PubMed 6421454Aarts 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.
- Background: PubMed 16751648Artama 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.
- Background: PubMed 14636777Binnie 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.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site 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 and Autism Spectrum Disorders, run by National Institute of Mental Health (NIMH) at 1 site 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 4 inclusion and 13 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 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
epileptiform EEG discharges (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01170325, which also lists 3 linked publications.
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 2 Jul 2017.