Autism Spectrum Disorder
Conditions
Keywords
autism, asperger's, repetitive, restricted, compulsions
Brief summary
This is an 8 week research study of aripiprazole (abilify) which is used to reduce irritable behaviors in autism spectrum disorders. All participants will receive active study medication. Participants will also receive diagnostic and cognitive evaluations at no cost. Participants will be required to undergo two fMRI (functional magnetic resonance imaging scans) where we will take pictures of your brain while performing simple tasks.
Interventions
DRUGAripiprazole
8 weeks, starting dosage 5mg titrating up 5mg every week as needed to maximum dosage of 25mg daily
Sponsors
Duke University
National Institute of Mental Health (NIMH)
University of North Carolina, Chapel Hill
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* male or female of any race or ethnicity * ambulatory status (outpatient) at time of consent * age 10-55 inclusive at time of consent * clinical diagnosis of autism spectrum disorder and meets screening criteria on the Social Communication Questionnaire as well as either the Autism Diagnostic Observation Schedule (ADOS) or the Autism Diagnostic Interview-Revised (ADI-R) administered by raters trained to research reliability. * estimated IQ greater than 70 and capable of making an informed decision based on assessment of their understanding and judgment * Children's Yale-Brown Obsessive Compulsive Scale: Modified for Pervasive Developmental Disorders (PDD-CYBOCS) \> 8 as assessed during telephone screening. * Free of psychoactive medication for at least: one month for fluoxetine; two weeks for other SSRIs and neuroleptics; and five days for stimulants prior to MRI scanning \[excepting stable doses (greater than three months duration) of anticonvulsant medication for seizure disorder\] * Currently taking psychoactive medication that is not providing sufficient relief of repetitive behaviors and willing to discontinue all psychoactive medication for the duration of the study. * Judged reliable for medication compliance and agreeing to keep follow-up study appointments.
Exclusion criteria
* Age less than 10 years or greater than 55 years at time of consent * Estimated IQ less than 70 * Uncontrolled epilepsy (seizure within 6 months prior to consent) * Presence of medical conditions that might interfere with participation, or where participation would be contraindicated. * History of neurological injury: head trauma, poorly-controlled seizure disorder (seizure within the preceding six months), stroke, prior neurosurgery, or under the care of a neurologist or neurosurgeon as determined by interview * History of claustrophobia * Implanted or irremovable metal in the body (including certain tattoos and permanent make-up). * Current pregnancy in females * Inability to communicate satisfactorily and directly (without a translator) in English * Medical contraindications to aripiprazole therapy as determined by history (including induction of neuroleptic malignant syndrome, dystonic reaction, or known drug allergy) * Ongoing need for psychoactive medication other than study medication \[excepting stable doses (greater than 3 months duration) of anticonvulsant medication for seizure disorder or diphenhydramine for sleep * prior history of aripiprazole treatment failure at appropriate doses and duration * clinically significant low white blood cell count at baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline and Week 8scores on Children's Yale-Brown Obsessive Compulsive Scale - Pervasive Developmental Disorder Version | Baseline (Pre-Dose) to 8 Weeks (Post-Dose) | The Children's Yale-Brown Obsessive Compulsive Scale - Pervasive Developmental Disorder Version (CY-BOCS-PDD) is a clinician-rated interview designed to evaluate repetitive behavior in children with pervasive developmental disorders (PDDs). It is a modification of the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), developed to assess typically-developing children with obsessive compulsive behavior. Because of language limitations in children with PDDs the CY-BOCS-PDD only includes the five compulsion items: Time Spent, Interference, Distress, Resistance of repetitive behavior, and Control of repetitive behavior. Each item is rated from 0 (none) through 4 (extreme), and scores can range from 0 to 20, with higher scores reflecting more severe symptoms. Usually a score \> than 8 is considered clinically significant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Repetitive Behavior Scale - Revised (RBS_R) | baseline week 0, 8 weeks | The RBS-R is an assessment that includes Sameness, Self-Injurious Behavior, Ritualistic, Compulsive, and Restrictive Behavior subscales. The assessments are completed by caregivers for the past week, with consideration of frequency,ease of redirecting and extent to which behavior interferes with functioning compared to a typically developing child of the same age and gender. Scores are rated from 0 - behavior does not occur to 3 - behavior occurs and is a serious problem. There are 43 items and 5 subscales. Higher scores indicate greater symptom severity. total score is the sum of all items in all subscales. The subscales are stereotyped behaviors 6 items, self-injurious behaviors 8 items, Compulsive behaviors- 8 items, Ritualistic Behaviors 6 items, Sameness 11 items, restricted behaviors 4 items.Total score ranges from 0 to 129. |
Countries
United States
Participant flow
Recruitment details
We planned to recruit participants through the NDRC Registry and Division TEACCH, as well as utilizing radio and television ads on various stations. We also posted brochures and flyers in public locations and attended conferences in order to hand out study-specific information. 13 subjects began the study and only one of those failed to complete.
Pre-assignment details
In order to participate in the research study, subjects must have been washed out from psychoactive medication for at least one month for fluoxetine, two weeks for other SSRIs and neuroleptics and five days for stimulants prior to MRI scanning, with the exception of stable doses greater than three months duration of medication for seizure disorder.
Participants by arm
| Arm | Count |
|---|---|
| Open-Label, Flexible-Dose Aripiprazole This is a single group assignment pharmacodynamics study in which all study participants are given an open-label, flexible dose of aripiprazole for up to 8 weeks.
Aripiprazole : 8 weeks, starting dosage 5mg titrating up 5mg every week as needed to maximum dosage of 25mg daily | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Open-Label, Flexible-Dose Aripiprazole |
|---|---|
| Age, Continuous | 20.31 years STANDARD_DEVIATION 5.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Baseline and Week 8scores on Children's Yale-Brown Obsessive Compulsive Scale - Pervasive Developmental Disorder Version
The Children's Yale-Brown Obsessive Compulsive Scale - Pervasive Developmental Disorder Version (CY-BOCS-PDD) is a clinician-rated interview designed to evaluate repetitive behavior in children with pervasive developmental disorders (PDDs). It is a modification of the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), developed to assess typically-developing children with obsessive compulsive behavior. Because of language limitations in children with PDDs the CY-BOCS-PDD only includes the five compulsion items: Time Spent, Interference, Distress, Resistance of repetitive behavior, and Control of repetitive behavior. Each item is rated from 0 (none) through 4 (extreme), and scores can range from 0 to 20, with higher scores reflecting more severe symptoms. Usually a score \> than 8 is considered clinically significant.
Time frame: Baseline (Pre-Dose) to 8 Weeks (Post-Dose)
Population: All randomized participants' scores were analyzed using the PDD-CYBOCS measure. Higher values reflect worse outcomes. Subscales are added to compute the total score (total score does not include compulsion free-interval and peculiarity of the behavior.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label, Flexible-Dose Aripiprazole: Baseline (Pre-Dose) | Baseline and Week 8scores on Children's Yale-Brown Obsessive Compulsive Scale - Pervasive Developmental Disorder Version | 12.7 Scores on a scale | Standard Deviation 2.25 |
| Open-Label, Flexible-Dose Aripiprazole: 8 Weeks (Post-Dose) | Baseline and Week 8scores on Children's Yale-Brown Obsessive Compulsive Scale - Pervasive Developmental Disorder Version | 8.6 Scores on a scale | Standard Deviation 3.5 |
Secondary
Total Repetitive Behavior Scale - Revised (RBS_R)
The RBS-R is an assessment that includes Sameness, Self-Injurious Behavior, Ritualistic, Compulsive, and Restrictive Behavior subscales. The assessments are completed by caregivers for the past week, with consideration of frequency,ease of redirecting and extent to which behavior interferes with functioning compared to a typically developing child of the same age and gender. Scores are rated from 0 - behavior does not occur to 3 - behavior occurs and is a serious problem. There are 43 items and 5 subscales. Higher scores indicate greater symptom severity. total score is the sum of all items in all subscales. The subscales are stereotyped behaviors 6 items, self-injurious behaviors 8 items, Compulsive behaviors- 8 items, Ritualistic Behaviors 6 items, Sameness 11 items, restricted behaviors 4 items.Total score ranges from 0 to 129.
Time frame: baseline week 0, 8 weeks
Population: All randomized participants' scores were analyzed using the RBS-R measure. Higher values reflect worse outcomes (greater symptom severity). Subscales are added to compute the total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label, Flexible-Dose Aripiprazole: Baseline (Pre-Dose) | Total Repetitive Behavior Scale - Revised (RBS_R) | 42.2 units on a scale | Standard Deviation 18.37 |
| Open-Label, Flexible-Dose Aripiprazole: 8 Weeks (Post-Dose) | Total Repetitive Behavior Scale - Revised (RBS_R) | 20.5 units on a scale | Standard Deviation 13.79 |