Methylphenidate for Attention Deficit Hyperactivity Disorder and Autism in Children

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Deborah Pearson, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT00178503
First received: September 12, 2005
Last updated: May 6, 2013
Last verified: May 2013

September 12, 2005
May 6, 2013
September 2005
May 2011   (final data collection date for primary outcome measure)
  • Mean Conners' Teacher ADHD Index T Score by Dose [ Time Frame: Measured at each dosing week of the drug trial (placebo, low, medium, high) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Measured at each dosing week of the drug trial (placebo, low, medium, high) ] [ Designated as safety issue: No ]
    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.
  • 1. Conners’ Teacher Rating Scale-Revised will be completed at study entry and at each week of the drug trial by the child's teacher as the primary measure of MPH response.
  • b. Matching Familiar Figures Test
  • c. Speeded Classification Task
  • d. Delay of Gratification Task
  • 2. Several cognitive measures will be used as primary measures of the child's cognitive response to MPH. These will be completed at study entry and at each week of the drug trial by the child and will include:
  • a. Continuous Performance Task
Complete list of historical versions of study NCT00178503 on ClinicalTrials.gov Archive Site
Mean Conners' Parent ADHD Index T Score by Week [ Time Frame: Measured at each dosing week of the drug trial (placebo, low, medium, high) ] [ Designated as safety issue: No ]
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.
  • 1. Parent rating measures will be completed at study entry and at each week of the drug trial by the child's parent as secondary measures of behavioral response to MPH, and will include:
  • a. Conners' Parent Rating Scale-Short Form
  • b. Side Effects Questionnaire
  • c. Aberrant Behavior Checklist
  • 2.Teacher rating measures will be completed at study entry and at each week of the drug trial by the child's teacher as secondary measures of behavioral response to MPH, and will include:
  • a. ADD-H Comprehensive Teacher Rating Scale
  • 3. Clinician ratings on the Clinical Global Impressions Scale will be completed at study entry and at each week of the drug trial by the study physician as a secondary measure of behavioral response to MPH.
  • 4. Other cognitive tasks (completed at study entry and each week of the MPH trial) will be completed as secondary measures of the child's cognitive response to MPH, including:
  • a. Selective Listening Task
  • b. Children's Embedded Figures Test
  • c. Stop Signal Test
Not Provided
Not Provided
 
Methylphenidate for Attention Deficit Hyperactivity Disorder and Autism in Children
ADHD Symptoms in Autism: Cognition, Behavior, Treatment

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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Autism
  • Attention Deficit Disorder With Hyperactivity
  • Drug: Methylphenidate-extended release
    Methylphenidate-extended release was taken in the morning of the MPH treatment trial. Each participant underwent 1 week of the each of the doses as determined by body weight. The lower body weight group (20 to 24 kg/44 to 52.8 lbs) took 10 mg Ritalin LA to 20 mg. The medium body weight group (25 to 33 kg/55 to 72.6 lbs) took from 10 mg Ritalin LA to 30 mg. The higher body weight group (34 to 59 kg/74.8 to 129.8 lbs) took 20 mg Ritalin LA to 40 mg.
    Other Name: Ritalin LA
  • Drug: Methylphenidate-immediate release
    Methylphenidate-immediate release was taken in the late afternoon. Each participant underwent 1 week at each of the 3 dose levels as determined by body weight. The lower body weight group (20 to 24 kg/44 to 52.8 lbs) took 2.5 mg IR-MPH and 2 weeks of 5 mg. The medium body weight group (25 to 33 kg/55 to 72.6 lbs) took 2 weeks of 5 mg IR-MPH and 1 week of 10 mg. The higher body weight group (34 to 59 kg/74.8 to 129.8 lbs) took 1 week of 5 mg IR-MPH and 2 weeks of 10 mg.
  • Other: Placebo
    Participants will take a placebo for 1 full week of the randomized drug trial. They will take one capsule in the morning and one capsule in the afternoon.
  • Placebo Comparator: MPH Trial-Placebo
    24 Participants with ASD-ADHD underwent 1 week of placebo in the MPH treatment phase
    Intervention: Other: Placebo
  • Active Comparator: MPH Trial: Low Dose
    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
    Interventions:
    • Drug: Methylphenidate-extended release
    • Drug: Methylphenidate-immediate release
  • Active Comparator: MPH Trial: Med Dose
    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
    Interventions:
    • Drug: Methylphenidate-extended release
    • Drug: Methylphenidate-immediate release
  • Active Comparator: MPH Trial: High Dose
    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
    Interventions:
    • Drug: Methylphenidate-extended release
    • Drug: Methylphenidate-immediate release
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
May 2011
May 2011   (final data collection date for primary outcome measure)

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
Both
7 Years to 12 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00178503
R01 MH072263, R01MH072263, DDTR B2-NDA
Yes
Deborah Pearson, The University of Texas Health Science Center, Houston
The University of Texas Health Science Center, Houston
National Institute of Mental Health (NIMH)
Principal Investigator: Deborah A. Pearson, PhD The University of Texas Health Science Center, Houston
The University of Texas Health Science Center, Houston
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP