Methylphenidate for Attention Deficit Hyperactivity Disorder and Autism in Children - Full Text View

Sponsored by:	National Institute of Mental Health (NIMH)
Information provided by:	National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00178503

Purpose

This study will first examine the cognitive and behavioral differences in children who have an autism spectrum disorder (ASD) and who do and do not have additional symptoms of attention deficit hyperactivity disorder (ADHD). The study will then examine the effectiveness of a range of doses of methylphenidate in improving cognitive and behavioral outcomes in children with both ASD and ADHD.

Condition	Intervention
Autism Attention Deficit Disorder With Hyperactivity	Drug: Methylphenidate-extended release Drug: Methylphenidate-instant release Other: Placebo

MedlinePlus related topics: Attention Deficit Hyperactivity Disorder Autism

Drug Information available for: Methylphenidate hydrochloride Methylphenidate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Efficacy Study
Official Title:	ADHD Symptoms in Autism: Cognition, Behavior, Treatment

Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:

Conners' Teacher Rating Scale-Revised (CTRS-R) [ Time Frame: Measured at study entry and at each week of the drug trial ] [ Designated as safety issue: No ]
Continuous Performance Test (CPT) [ Time Frame: Measured at study entry and at each week of the drug trial ] [ Designated as safety issue: No ]
Matching Familiar Figures Test (MFFT) [ Time Frame: Measured at study entry and at each week of the drug trial ] [ Designated as safety issue: No ]
Speeded Classification Task (SCT) [ Time Frame: Measured at study entry and at each week of the drug trial ] [ Designated as safety issue: No ]
Delay of Gratification Task (DOG) [ Time Frame: Measured at study entry and at each week of the drug trial ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Conners' Parent Rating Scale (CPRS)-Short Form [ Time Frame: Measured at study entry and at each week of the drug trial ] [ Designated as safety issue: No ]
Side Effects Questionnaire-Parent Version [ Time Frame: Measured at study entry and at each week of the drug trial ] [ Designated as safety issue: Yes ]
Aberrant Behavior Checklist [ Time Frame: Measured at study entry and at each week of the drug trial ] [ Designated as safety issue: No ]
ADDH Comprehensive Teacher Rating Scale [ Time Frame: Measured at study entry and at each week of the drug trial ] [ Designated as safety issue: No ]
Side Effects Questionnaire-Teacher Version [ Time Frame: Measured at study entry and at each week of the drug trial ] [ Designated as safety issue: Yes ]
Clinician ratings on the Clinical Global Impressions Scale [ Time Frame: Measured at study entry and at each week of the drug trial ] [ Designated as safety issue: No ]
Selective Listening Tasks (pediatric speech intelligibility and dichotic listening tasks) [ Time Frame: Measured at study entry and at each week of the drug trial ] [ Designated as safety issue: No ]
Stop Signal Test [ Time Frame: Measured at study entry and at each week of the drug trial ] [ Designated as safety issue: No ]

Estimated Enrollment:	72
Study Start Date:	September 2005
Estimated Study Completion Date:	May 2010
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
ASD/ADHD Group: No Intervention Participants with autism and symptoms of ADHD who will undergo the initial psychological testing phase and will be compared to the autism-only group for behavioral, cognitive, and emotional differences
ASD/non-ADHD group: No Intervention Participants with autism and do not have symptoms of ADHD who will undergo the initial psychological testing phase and will be compared to the autism-ADHD group for behavioral, cognitive, and emotional differences
MPH Trial-Placebo: Placebo Comparator Participants with ASD-ADHD who will undergo 2 weeks of placebo in the MPH treatment phase	Other: Placebo Participants will take a placebo for 1 full week of the randomized drug trial. They will take one pill in the morning and one pill in the afternoon.
MPH Trial: Low Dose: Active Comparator Participants with ASD-ADHD who will undergo 1 week at a low dose of MPH in the MPH treatment phase	Drug: Methylphenidate-extended release Methylphenidate-extended release will be taken in the morning of the MPH treatment trial. Each participant will undergo 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) will start at 10 mg Ritalin LA and will increase to 20 mg. The medium body weight group (25 to 33 kg/55 to 72.6 lbs) will start at 10 mg Ritalin LA and will increase to 30 mg. The higher body weight group (34 to 59 kg/74.8 to 129.8 lbs) will start at 20 mg Ritalin LA and will increase to 40 mg. Drug: Methylphenidate-instant release Methylphenidate-instant release will be taken in the evening. Each participant will undergo 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) will take 2.5 mg IR-MPH and then 2 weeks of 5 mg. The medium body weight group (25 to 33 kg/55 to 72.6 lbs) will take 2 weeks of 5 mg IR-MPH and then 1 week of 10 mg. The higher body weight group (34 to 59 kg/74.8 to 129.8 lbs) will take 1 week of 5 mg IR-MPH and then 2 weeks of 10 mg.
MPH Trial: Med Dose: Active Comparator Participants with ASD-ADHD who will undergo 1 week at a medium dose of MPH in the MPH treatment phase	Drug: Methylphenidate-extended release Methylphenidate-extended release will be taken in the morning of the MPH treatment trial. Each participant will undergo 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) will start at 10 mg Ritalin LA and will increase to 20 mg. The medium body weight group (25 to 33 kg/55 to 72.6 lbs) will start at 10 mg Ritalin LA and will increase to 30 mg. The higher body weight group (34 to 59 kg/74.8 to 129.8 lbs) will start at 20 mg Ritalin LA and will increase to 40 mg. Drug: Methylphenidate-instant release Methylphenidate-instant release will be taken in the evening. Each participant will undergo 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) will take 2.5 mg IR-MPH and then 2 weeks of 5 mg. The medium body weight group (25 to 33 kg/55 to 72.6 lbs) will take 2 weeks of 5 mg IR-MPH and then 1 week of 10 mg. The higher body weight group (34 to 59 kg/74.8 to 129.8 lbs) will take 1 week of 5 mg IR-MPH and then 2 weeks of 10 mg.
MPH Trial: High Dose: Active Comparator Participants with ASD-ADHD who will undergo 1 week at a high dose of MPH in the MPH treatment phase	Drug: Methylphenidate-extended release Methylphenidate-extended release will be taken in the morning of the MPH treatment trial. Each participant will undergo 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) will start at 10 mg Ritalin LA and will increase to 20 mg. The medium body weight group (25 to 33 kg/55 to 72.6 lbs) will start at 10 mg Ritalin LA and will increase to 30 mg. The higher body weight group (34 to 59 kg/74.8 to 129.8 lbs) will start at 20 mg Ritalin LA and will increase to 40 mg. Drug: Methylphenidate-instant release Methylphenidate-instant release will be taken in the evening. Each participant will undergo 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) will take 2.5 mg IR-MPH and then 2 weeks of 5 mg. The medium body weight group (25 to 33 kg/55 to 72.6 lbs) will take 2 weeks of 5 mg IR-MPH and then 1 week of 10 mg. The higher body weight group (34 to 59 kg/74.8 to 129.8 lbs) will take 1 week of 5 mg IR-MPH and then 2 weeks of 10 mg.

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.

Two groups of participants between the ages of 7 to 12 will participate in the initial phase of the study to examine the differences in children who have an Autism Spectrum Disorder with or without additional symptoms of ADHD. In one group, participants will qualify for a diagnosis of an Autism Spectrum Disorder (Autistic Disorder, Asperger's Disorder, and Pervasive Developmental Disorder-Not Otherwise Specified) and will also have symptoms of ADHD (ASD/ADHD), while in the second group, participants will have an Autism Spectrum Disorder, without symptoms of ADHD (ASD/non-ADHD group). All participants will undergo an initial psychological testing session that includes 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 will be excluded. The participants who meet eligibility criteria will complete computerized tasks of attentional functioning in a second visit (Visit 2).

A subset of the children from the ASD/ADHD group (N=24) will be invited to participate in a six-week randomized double-blind, placebo-controlled treatment trial using various doses (low, medium, or high dose) of methylphenidate (MPH). Children who are invited to participate 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 child will take one of the three doses of MPH or a placebo. At the end of each week the child will be brought into the clinic by the parent for 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 will be asked to complete questionnaires about the child's behavior each week, so that the child's home and school behaviors at each MPH dose can be assessed.

Eligibility

Ages Eligible for Study:	7 Years to 12 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00178503

Contacts

Contact: Rosleen Mansour, MA

713-500-2580

Rosleen.Mansour@uth.tmc.edu

Locations

United States, Texas
University of Texas Health Science Center at Houston	Recruiting
Houston, Texas, United States, 77030
Contact: Rosleen Mansour, MA 713-500-2580 Rosleen.Mansour@uth.tmc.edu
Principal Investigator: Deborah A. Pearson, PhD
Sub-Investigator: Cynthia W. Santos, MD
Sub-Investigator: Katherine A. Loveland, PhD

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:

Deborah A. Pearson, PhD

The University of Texas Health Science Center, Houston

More Information

Click here for more information on this study on the Clinic Website This link exits the ClinicalTrials.gov site

Responsible Party:	The University of Texas Health Science Center at Houston ( Deborah A. Pearson, PhD/Professor )
Study ID Numbers:	R01 MH72263, DDTR B2-NDA
Study First Received:	September 12, 2005
Last Updated:	July 2, 2008
ClinicalTrials.gov Identifier:	NCT00178503
Health Authority:	United States: Federal Government

Study placed in the following topic categories:

Developmental Disabilities
Attention Deficit and Disruptive Behavior Disorders
Methylphenidate
Dyskinesias
Child Development Disorders, Pervasive
Signs and Symptoms
Dopamine

Attention Deficit Disorder with Hyperactivity
Autistic Disorder
Mental Disorders
Mental Disorders Diagnosed in Childhood
Hyperkinesis
Neurologic Manifestations

Additional relevant MeSH terms:

Dopamine Uptake Inhibitors
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Disease
Molecular Mechanisms of Pharmacological Action
Nervous System Diseases
Physiological Effects of Drugs

Central Nervous System Stimulants
Pharmacologic Actions
Pathologic Processes
Therapeutic Uses
Dopamine Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 14, 2009