Response Variability in Children With Attention Deficit Hyperactivity Disorder (ADHD)
Condition: Attention Deficit Hyperactivity Disorder
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Intervention: Methylphenidate; placebo; Methylphenidate; Methylphenidate
Intervention description: 18 mg methylphenidate; Placebo; 36 mg methylphenidate; 54 mg methylphenidate
Intervention MeSH terms: Methylphenidate
Phase: Phase 4
Study type: Interventional
Primary purpose: Health Services Research
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 96.0
Sex: All
Minimum age: 7 Years
Maximum age: 11 Years
Healthy volunteers: No

Summary:

      Children with Attention Deficit Hyperactivity Disorder (ADHD) have numerous areas of
      neuropsychological dysfunction including response inhibition, working memory, and attention.
      One neuropsychological outcome measure that consistently reveals between-group differences is
      response variability. However, until recently, differences in response variability have been
      reported as an ancillary finding or viewed as a nuisance in the analyses. The specific aims
      of the present study are to 1) Examine response variability in ADHD patients across
      neuropsychological tasks to understand the breadth of this specific deficit and to understand
      the relation between response variability and other neuropsychological outcome measures; 2)
      Assess whether response variability deficits are specific to either or both of the two most
      prevalent ADHD subtypes (i.e., Combined Type [CT] and Predominantly Inattentive Type [PIT]);
      3) Determine whether response variability in ADHD patients is affected by either medication
      or a variety of environmental manipulations (e.g., reward); and 4) Understand the
      relationship between neuropsychological measures of response variability and naturalistic
      instances of variable performance. Forty-five children (aged 7-11) with ADHD-CT, 45 children
      with ADHD-PIT, and 45 normal controls will be recruited to examine response variability
      across a wide range of neuropsychological tests. Task parameters such as event rate, stimulus
      saliency, and the presence of operant reward will be modified on each test to determine the
      conditions under which response variability is manifested in children with ADHD. In addition,
      all children with ADHD will participate in a placebo-controlled, randomized medication trial
      with a psychostimulant medication to assess the effects of medication on response
      variability. Advanced analytic methods utilizing non-Gaussian distributions and fast Fourier
      Transforms of the reaction time data will be used to conduct detailed analyses of RT patterns
      across the ADHD and normal control groups. Further, the effects of task parametric
      manipulations and medication on response variability will be examined. Finally, relations
      between response variability on neuropsychological tests and response variability in a
      variety of real-world analog situations will be examined to evaluate the ecological validity
      of these deficits.
    

Eligibility criteria:

        Inclusion Criteria. Participants for the study must meet all of the following criteria:

          1. Consent: The family must provide signature of informed consent by parents or legal
             guardians.

          2. Age at time of Screening: 7 years to 11 years, inclusive

          3. Gender: includes male and female children.

          4. ADHD Diagnostic Status: ADHD patients must meet DSM-IV criteria for ADHD, Inattentive
             or Combined subtype. Normal controls must not meet DSM-IV criteria for ADHD, any
             subtype. Section D.4 below describes in detail the diagnostic process for arriving at
             diagnosis.

          5. Cognitive Functioning: IQ of greater than 80 as estimated by Vocabulary and Block
             Design subtests of the Wechsler Intelligence Scale for Children, Fourth Edition
             (WISC-IV).

          6. Learning Disability: All children will be administered the abbreviated WIAT including
             the Spelling, Reading, and Math subtests. Children must score above 80 on all three
             WIAT subtests.

          7. School: Children must be enrolled in a school setting from which teacher ratings can
             be obtained.

        Exclusion Criteria. Potential participants will be excluded if they meet any of the
        following criteria:

          1. Understanding Level. The patient and parent cannot understand or follow instructions
             given in the study.

          2. History of Psychiatric Medications: Children who have a history of taking any
             medication for psychological or psychiatric problems will be excluded from
             participation.

          3. Exclusionary Psychiatric Conditions: Children whose primary diagnosis is something
             other than ADHD will be excluded from participation.

          4. Developmental Disabilities. As a result of scores on the IQ screening, additional
             assessments, or the judgment of the study clinicians, patients will be excluded if
             they are deemed to be significantly developmentally delayed. This includes clinically
             significant delays in cognitive function or the presence of other Pervasive
             Developmental Disorders (PDD).

          5. Organic Brain Injury: Children must not have a history of head trauma, neurological
             disorder, or any other organic disorder that could possibly affect brain function.