Attention Deficit Disorder Medication Response Study
Condition: ADHD - Inattentive Type; ADHD - Combined Type
MeSH terms: Attention Deficit Disorder with Hyperactivity
Intervention: OROS-Methylphenidate and placebo for inattentive type pts; OROS-Methylphenidate and placebo for combined type pts
Intervention description: Every participant receives low dose MPH, medium dose MPH, high dose MPH, and placebo for one week each in a triple-blinded fashion.; Every participant receives low dose MPH, medium dose MPH, high dose MPH, and placebo for one week each in a triple-blinded fashion.
Intervention MeSH terms: Methylphenidate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Every participant receives placebo and three different dose of MPH for one week each in a triple blinded fashion
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 171.0
Sex: All
Minimum age: 7 Years
Maximum age: 11 Years
Healthy volunteers: No
Keywords: ADHD; Inattention; Methylphenidate; Pharmacogenetics

Summary:

      This study evaluates how children with Attention Deficit Disorder without Hyperactivity (ADD)
      respond to medication, and if their response is different from children who have problems
      with both hyperactivity and inattention. In order to do this, children ages 7-11 whose
      primary difficulty is with attention problems and who have never been on behavioral or
      psychiatric medications are being recruited. Once enrolled, children will try one week each
      of 3 different doses of methylphenidate, the most commonly prescribed Attention Deficit,
      Hyperactivity Disorder (ADHD) medication, as well as placebo. Children will be randomly
      assigned to one of six possible medication dose and placebo titration schedules, but the
      study doctor, family, and teacher will not know which dose (if any) children are receiving
      for a given week. Each week, behavioral and side effect ratings will be completed by both the
      child's parent and teacher, and the family will meet with the study doctor for a physical
      examination and to discuss how each week went. Some children will also have
      neuropsychological testing to determine how methylphenidate influences their working memory,
      sustained attention, and ability to inhibit (stop) inappropriate responses.

      All data will be analyzed to decide which medication dose the child responded to best and
      further recommendations for treatment will be given. Ultimately, this study aims to improve
      understanding of how children with ADHD-Primarily Inattentive Type respond to stimulant
      medications by

        -  determining whether these children experience a diminished response to methylphenidate
           compared to children with both hyperactivity and inattention

        -  determining whether certain genetic and environmental factors play a role in this
           response.

      Findings from this study will be used to help streamline the identification of the most
      effective doses of medication for children with ADHD-Primarily Inattentive Type.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Consent: The family must provide signature of informed consent by a parent or legal
             guardian. Children must also assent to study participation.

          -  Age at Screening:7.0 years to 11.9 years, inclusive.

          -  Sex: Includes male and female children.

          -  ADHD Diagnostic Status: Meets DSM-IV criteria for ADHD, Predominantly Inattentive or
             Combined subtype with Clinical Global Impression-Severity rating corresponding to at
             least "moderately ill."

          -  Cognitive Functioning-Intelligence Quotient (IQ) of greater than 80 as estimated by
             Vocabulary and Block Design subtests of the Wechsler Intelligence Scale for
             Children--4th Edition, or an Intelligence Quotient (IQ) of 80 or greater when
             administered the Full Scale Version of the Wechsler Intelligence Scale for
             Children-4th Edition.

          -  Absence of Learning Disability:On the abbreviated Wechsler Individual Achievement
             Test-2nd edition Reading and Math subtests, participants must score above 80. However,
             children may also be included if they receive a score of 75 or greater on the Word
             Reading and/or Math subtests, as long as this score is not a significant discrepancy
             from their full-scale IQ score (e.g., a difference of greater than one standard
             deviation or 15 points).

          -  School: Enrolled in a school setting rather than a home-school program.

        Exclusion Criteria:

          -  Understanding Level: Participant and/or parent cannot understand or follow study
             instructions.

          -  Psychiatric Medications: Current or prior history of taking any medication for
             psychological or psychiatric problems.

          -  Behavioral Interventions: Current active participation in ADHD-related behavioral
             interventions or counseling.

          -  Exclusionary Psychiatric Conditions: Children with mania/hypomania and/or
             schizophrenia will be excluded. The following comorbid diagnoses will not be excluded
             unless they are determined to be the primary cause of ADHD symptomatology (see below
             for description of this decision process): Post Traumatic Stress Disorder, Phobias and
             Anxiety Disorders, Obsessive Compulsive Disorder, Major Depression / Dysthymia, Eating
             Disorders, Elimination Disorders, Trichotillomania, Tic Disorder, Oppositional Defiant
             Disorder, Conduct Disorder.

          -  Organic Brain Injury: History of head trauma, neurological disorder, or other organic
             disorder affecting brain function.

          -  Cardiovascular Risk Factors: Children with a personal history or family history of
             cardiovascular risk factors will be excluded, or given the option of participating in
             the study after obtaining an EKG and a signed letter from a pediatric cardiologist
             verifying the safety of their participation in a trial of methylphenidate. In this
             case, families will be responsible for the costs of EKG and cardiologist evaluation.
             If for any reason a family is unable to assume the cost of the EKG and cardiologist
             evaluations but still wishes for their child to participate, study staff will
             determine on a case-by-case basis whether the study budget allows the study to offer
             financial assistance to the families for these evaluations.