Attention Deficit Disorder Medication Response Study
Condition: ADHD - Inattentive Type; ADHD - Combined Type
MeSH terms: Attention Deficit Disorder with Hyperactivity
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      Robust data indicate that stimulant medications reduce ADHD symptoms and impairment, but it
      is unclear whether their efficacy generalizes across the ADHD subtypes. Although
      predominately inattentive type (PIT) is the most prevalent ADHD subtype in U.S.
      population-based studies, few studies have specifically examined response to stimulants in
      this subtype. Instead, medication guidelines for PIT have largely been extrapolated from
      studies enrolling all or mostly ADHD-combined type (CT). Thus, this application seeks to
      improve understanding of stimulant medication response and its predictors in children with
      PIT. We will evaluate participants' response to methylphenidate (MPH), the most widely
      prescribed stimulant, via a prospective, double-blind, placebo-controlled crossover trial
      with 3 dose conditions. Our first specific aim is to examine MPH medication and dose response
      in children with PIT (n=120) and CT (n=45) to test the hypotheses that participants with PIT
      have a diminished MPH response and derive less benefit from higher doses compared to those
      with CT. Since only one prior study has examined genetic predictors of MPH response
      variability within PIT-only samples, our second specific aim (exploratory) is to determine
      the potential role of genetic polymorphisms (e.g., those in DAT1, DRD4, NET, ADRA2A, COMT,
      SNAP25, CES1, GRM7, LPHN3) on MPH response in children with PIT (n=120), examining both
      symptom change with MPH and MPH dose response curves. If we identify significant differences
      in MPH response between the subtypes, our findings may guide clinical practice by suggesting
      more effective medication strategies (such as different dosing schedules) for children with
      PIT. In addition, this study may yield pharmacogenetic findings that, in the future, could
      enable physicians to tailor individual treatment plans for children with PIT, ameliorating
      the current prolonged and expensive practice of prescribing by trial and error.
    

Intervention name(s): OROS-Methylphenidate and placebo for inattentive type pts; OROS-Methylphenidate and placebo for combined type pts
Intervention type(s): Drug; Drug
Intervention description(s): 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.
Other intervention name(s): concerta
Intervention MeSH terms: Methylphenidate
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)
Primary purpose: Treatment
Keywords: ADHD; Inattention; Methylphenidate; Pharmacogenetics