Methylphenidate for Attention Deficit Hyperactivity Disorder and Autism in Children

Phase 2

Completed

Conditions: Autism
Attention Deficit Disorder With Hyperactivity

Interventions: Other: Placebo
Drug: Methylphenidate-extended release
Drug: Methylphenidate-immediate release

Registration Number: NCT00178503

Lead Sponsor: The University of Texas Health Science Center, Houston

Brief Summary: This study examined the cognitive and behavioral differences in children who have an autism spectrum disorder (ASD) with or without additional symptoms of ADHD. The study also examined the effectiveness of a range of doses of methylphenidate in improving cognitive and behavioral outcomes in children with both ASD and ADHD.

Detailed Description: Attention Deficit Hyperactivity Disorder (ADHD) is a major comorbid psychiatric disorder in children with Autism Spectrum Disorders (ASD) that significantly undermines behavioral, social, and emotional adjustment. Although the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) does not specifically allow for a comorbid diagnosis of ADHD with ASD, many children with an ASD manifest symptoms of ADHD and are treated for it with stimulants or other medication. The few studies on ADHD in ASD have not consistently established its cognitive and behavioral manifestations, or the optimal parameters for treatment. The proposed project will address these issues through studies of cognitive and behavioral functioning in children with ASD, with and without ADHD, and through a study of medication treatment of ADHD symptoms in autism.

Participants between the ages of 7 to 12 with an autism spectrum disorder participated in the initial phase of the study to examine the nature and effects of ADHD symptoms on behavioral and cognitive functioning. Participants underwent an initial psychological testing session that included standardized measures of intellectual, adaptive behavior, language, behavioral, and emotional functioning, along with standardized diagnostic measures to confirm their diagnoses of ASD and/or ADHD (Visit 1). Children with intelligence quotients (IQs) below 50 or greater than 130 or with major sensory, motor, neurological, genetic, or psychiatric disorders that may interfere with testing were be excluded. The participants who meet eligibility criteria completed computerized tasks of attentional functioning in a second visit (Visit 2).

A subset of the children meeting criteria for the ASD/ADHD group (N=24) participated in a six-week randomized double-blind, placebo-controlled treatment trial using various doses (low, medium, or high dose) of methylphenidate (MPH). Children participated in the treatment trial will be those who qualified based on the initial phase and who do not have any physical contraindications to MPH (e.g., history of MPH intolerance). In each week of the treatment trial, the children took one of the three doses of MPH or a placebo. At the end of each week the child were evaluated in the clinic by including a medical check-up, parent interviews about the child's behavior and functioning that week, and computerized cognitive testing. Additionally, the child's parent and teacher completed questionnaires about the child's behavior each week, so that the child's home and school behaviors at each MPH dose could be assessed.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

Inclusion Criteria

Autism/ADHD Group:

DSM-IV diagnosis of autistic disorder, as per the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS)
Child manifests current symptoms of ADHD

Autism/non-ADHD Group:

Meets the diagnostic criteria for autism, as above, but does not meet the diagnostic criteria for ADHD

Exclusion Criteria

In both groups, exclusion criteria will include:

Sensory or motor deficits sufficient to interfere with testing (e.g., blindness, severe cerebral palsy)
Serious neurological disorders (e.g., epilepsy, stroke)
Down syndrome, fragile X syndrome, Tourette syndrome, or fetal alcohol syndrome
Bipolar disorder or a family history of bipolar disorder in a first-degree relative
Other serious psychopathology that resulted in psychiatric hospitalization (e.g., for psychotic episode). The investigators will screen for this using the Diagnostic Interview for Children and Adolescents (DICA)-IV, and getting a complete developmental/medical history
Serious physical handicaps that would interfere with performance on laboratory tasks
IQ less than 50 and greater than 130
Verbal mental age (VMA) less than 36 months (to exclude participants unable to understand simple task instructions)

In the autism/ADHD group, further exclusion criteria apply to the MPH trial:

History of intolerance to MPH
Weight less than 20 kg or greater than 59 kg (less than 44 pounds or greater than 130 pounds)
Concomitant use of dextroamphetamine preparations (Dexedrine, Dextrostat), mixed amphetamine salts (Adderall XR), other MPH preparations (e.g., Concerta, Metadate); venlafaxine, bupropion, atomoxetine, guanfacine, modafinil.
Concomitant use of any herbal preparations
Medical condition for which stimulants are contraindicated (e.g., high blood pressure)
Past treatment failure on a methylphenidate trial

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MPH Trial-Placebo	Placebo	24 Participants with ASD-ADHD underwent 1 week of placebo in the MPH treatment phase
MPH Trial: Low Dose	Methylphenidate-extended release	24 Participants with ASD-ADHD underwent 1 week at a low dose of Methylphenidate-extended release and Methylphenidate-immediate release in the MPH treatment phase
MPH Trial: Low Dose	Methylphenidate-immediate release	24 Participants with ASD-ADHD underwent 1 week at a low dose of Methylphenidate-extended release and Methylphenidate-immediate release in the MPH treatment phase
MPH Trial: Med Dose	Methylphenidate-extended release	24 Participants with ASD-ADHD underwent 1 week at a medium dose of Methylphenidate-extended release and Methylphenidate-immediate release in the MPH treatment phase
MPH Trial: Med Dose	Methylphenidate-immediate release	24 Participants with ASD-ADHD underwent 1 week at a medium dose of Methylphenidate-extended release and Methylphenidate-immediate release in the MPH treatment phase
MPH Trial: High Dose	Methylphenidate-extended release	24 Participants with ASD-ADHD underwent 1 week at a high dose of Methylphenidate-extended release and Methylphenidate-immediate release in the MPH treatment phase
MPH Trial: High Dose	Methylphenidate-immediate release	24 Participants with ASD-ADHD underwent 1 week at a high dose of Methylphenidate-extended release and Methylphenidate-immediate release in the MPH treatment phase

Primary Outcome Measures

Name	Time	Method
Mean Conners' Teacher ADHD Index T Score by Dose	Measured at each dosing week of the drug trial (placebo, low, medium, high)	The ADHD Index of the Conners' Teacher Rating Scale-Revised (CTRS-R) assesses symptoms associated with ADHD, including inattentiveness, hyperactivity and impulsivity. Lower T-scores on this subscale are associated with milder ADHD symptoms. T-scores have a mean of 50 and a SD of 10. Thus, T-scores of 70+ (i.e., 2 SD's over the mean) on the ADHD Index are suggestive of very significant ADHD symptomatology. Treatment-related changes of 5+ points are considered to be significant.
Mean Continuous Performance Test (CPT)-Commission Errors by Dose	Measured at each dosing week of the drug trial (placebo, low, medium, high)	CPT is a measure of sustained attention using nonverbal stimuli (pictures). Participants are asked to click on the witch (target), which appears for 25% of the trials. Commission errors are measured by number of times they click for the non-target items.

Secondary Outcome Measures

Name	Time	Method
Mean Conners' Parent ADHD Index T Score by Week	Measured at each dosing week of the drug trial (placebo, low, medium, high)	The ADHD Index of the Conners' Parent Rating Scale-Revised (CPRS-R) assesses symptoms associated with ADHD, including inattentiveness, hyperactivity and impulsivity. Lower T-scores on this subscale are associated with milder ADHD symptoms. T-scores have a mean of 50 and a SD of 10. Thus, T-scores of 70+ (i.e., 2 SD's over the mean) on the ADHD Index are suggestive of very significant ADHD symptomatology. Treatment-related changes of 5+ points are considered to be significant.