Genetic Measurements in Blood Cells of Children Taking Adderall or Methylphenidate
Condition: Attention Deficit Hyperactivity Disorder; ADHD
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Study type: Observational

Summary: 
      This study, conducted at Duke University in Durham, NC, will determine whether the drugs
      Adderall and methylphenidate affect the genetic material of children with attention deficit
      hyperactivity disorder (ADHD). One small study has shown that taking methylphenidate for ADHD
      may result in higher levels of certain types of changes to the genetic material contained in
      white blood cells. The changes seen are not directly linked to increased risk of disease, but
      indicate a possibility that other kinds of damage that may be linked to increased disease may
      result from taking methylphenidate. The study will also examine whether these types of
      changes might occur in children treated with Adderall .

      Children between the ages of 6 and 12 with symptoms of ADHD may be eligible for this study.
      Candidates are screened with a medical history, psychiatric examination, IQ test, physical
      examination, and electrocardiogram. Parents and teachers complete questionnaires to rate the
      severity of the child's ADHD. Qualified children who are diagnosed with ADHD and who are
      appropriate candidates for treatment with either Adderall or methylphenidate-based drugs
      (e.g., Concerta, Metadate, Focalin, Ritalin or Ritalin LA) may be selected for this study.

      At a baseline visit (Visit 0), parents complete questionnaires that rate the severity of
      their child's ADHD. The children have their vital signs checked (pulse, blood pressure,
      breathing rate, height, weight and temperature) and have a blood sample drawn. The children
      are then randomly assigned to treatment with either Adderall or a methylphenidate product.
      After the baseline visit, participants undergo the following tests and procedures:

      Dose Optimization Visits (visits 1-4)

      In the first 4 weeks of the study, the dose of methylphenidate or Adderall is adjusted weekly
      until doctors determine the dose strength that works best for the individual child. In
      addition, the following procedures are done at each visit:

        -  Child's vital signs are checked.

        -  Parents complete a questionnaire about the severity of the child's ADHD.

        -  Parent and child describe the impact of symptoms on the child's functioning.

        -  Parents complete forms about common side effects of the study drug.

      Follow-up Visits (visits 5-6)

      Children return to the clinic once a month to assess their health and further adjust their
      medication dose, if needed. The visits are similar to those during the dose optimization
      period, with the following additional procedures at visit 6:

        -  A blood sample is obtained to measure whether the medication has affected the child's
           genetic material.

        -  A physical examination is done to check child's health.

        -  Information is provided parents to assist in planning for child's treatment after the
           study.
    

Detailed description: 
      Design: Longitudinal observational study of pediatric ADHD patients, any subtype. This study
      is part of a large comprehensive investigation initiated and funded by the National Institute
      of Child Health and Human Development to aid in the understanding of a reported association
      of methylphenidate treatment and elevated frequencies of some types of chromosome damage.

      Population: 60 diagnosed ADHD children, age range 6-12 years inclusive, for whom
      pharmacological treatment with stimulant medication is indicated. 30 children will initiate
      treatment with a methylphenidate-based product and 30 will initiate treatment with Adderall
      or Adderall-XR. Study group assignment will be randomized, as these two drugs are considered
      by the clinical community to be fully interchangeable.

      Primary Objective: To determine the frequency of micronuclei (markers of numerical or
      structural chromosomal damage), sister chromatid exchanges (indicators of DNA damage), and
      chromosomal aberrations in lymphocytes of pediatric ADHD patients prior to and after 3 months
      of uninterrupted drug therapy. These endpoints, and the time frame, are compatible with
      investigating effects during the initiation phase of treatment; additional studies by other
      NIH institutes (NIMH, CDC) will investigate effects after chronic treatment with stimulant
      medications so that a comprehensive picture of the potential for treatment-induced
      chromosomal damage in ADHD subjects is obtained.

      Secondary Objective: In pediatric ADHD patients treated with a methylphenidate-based product
      or Adderall, to determine if flow cytometric measurement of the frequency of micronucleated
      erythrocytes can serve as a biomarker of cytogenetic damage in lymphocytes evaluated by
      standard light microscope techniques.
    

Keywords: Longitudinal Study; Chromosomal Effects; Sister Chromatid Exchanges; Micronuclei; Stimulants; Attention Deficit Hyperactivity Disorder; ADHD