Treatment of Severe Childhood Aggression (The TOSCA Study)
Condition: Attention Deficit Disorder With Hyperactivity
MeSH terms: Attention Deficit Disorder with Hyperactivity; Aggression
Study type: Interventional
Phase: Phase 4

Summary: 
      This study will determine the safety and effectiveness of two medications for treating
      aggression in children with attention deficit hyperactivity disorder (ADHD).
    

Detailed description: 
      ADHD is characterized by inattention, impulsivity, and hyperactivity. Children with ADHD
      sometimes also have disruptive behavior disorders (DBDs), such as conduct disorder (CD),
      which is estimated to develop in 20% to 40% of children with ADHD, and oppositional defiant
      disorder (ODD), which is estimated to develop in 33% to 50% of children with ADHD. These two
      disorders place youth at risk of other psychiatric disorders, especially substance abuse
      disorders. Several medications have been tested to treat conduct disorders in aggressive
      children, and, among these, risperidone and methylphenidate hydrochloride (HCl) have
      relatively good records of safety and tolerability. Psychostimulants, such as methylphenidate
      HCl, can reduce the symptoms in some, but not all, children with DBDs. Combining
      methylphenidate HCl with risperidone may be one way to increase the effectiveness of drug
      treatments. This study will compare the effectiveness of methylphenidate HCl alone versus
      methylphenidate HCl combined with risperidone for treating aggressive behavior in children
      with ADHD. Participation in this study will last 1 year. The child participant and a parent
      will attend all study visits. Two initial visits will involve a battery of baseline tests,
      including a psychological clinical interview, physical examination, lab tests, and an
      electrocardiogram (ECG). The parents will undergo a parent education session and complete
      questionnaires about their child's behavior, emotions, and medication side effects. The child
      will have his or her vital signs measured and complete tests of verbal memory and attention
      and impulsiveness. After the second visit, the child participant will be randomly assigned to
      receive either methylphenidate HCl alone or methylphenidate HCl plus risperidone.

      For the next 3 weeks, all child participants will take methylphenidate HCl at a dose that
      will start low and gradually be increased until the most effective dose is determined. For
      the next 6 weeks, child participants will add either risperidone or a placebo to their
      regimen of methylphenidate HCl. This second medication will also be started at a low dose and
      raised to appropriate levels of tolerability. During the 9 weeks of medication adjustment,
      participants will attend weekly study visits to complete questionnaires and have their vital
      signs measured. Parents will attend education sessions at each of these visits. The child's
      teacher will also fill out weekly questionnaires on the child's behavior. Every 3 weeks,
      child participants will be tested on verbal memory, attention, and impulsiveness. After the
      9-week period, child participants will again undergo a physical exam, lab tests, and an ECG.

      At this point, if the child's behavior has improved, the child will continue the same
      treatment for the next 3 months. Monthly study visits will include parent education sessions
      and recording of parent and teacher evaluations of the child. All participants will attend a
      1-year follow-up visit that will include previous assessments.
    

Intervention name(s): Methylphenidate HCl; Risperidone; Parent Management Training (PMT); Placebo
Intervention type(s): Drug; Drug; Behavioral; Drug
Intervention description(s): For children weighing less than 25 kg, the dose will be titrated at 18 mg for the first 7 days, 36 mg for the next 4 days, and, if needed, 54 mg for the next 4 days. For children weighing more than 25 kg, the dose will be titrated at 18 mg for the first 4 days, 36 mg for the next 3 days, 54 mg for the next 4 days, and 72 mg for the next 3 days.
Once the child's optimal dose is established, he or she will continue on that dose for the rest of the 21-week trial.
One pill is taken once daily.; For children weighing less than 45 kg, the dose will start at 0.5 mg at night. After 4 days, the child's dose may be increased to 1 mg a day. On Day 8, the child's dose may be increased to 1.5 mg a day. On Day 16, the child's dose may be increased to 2.0 mg a day. On Day 22, the child's dose may be increased to 2.5 mg a day.
For children weighing more than 45 kg, the dose will start at 0.5 mg at night. After 4 days, the child's dose may be increased to 1.0 mg a day. On Day 8, the child's dose may be increased to 1.5 mg a day. On Day 12, the child's dose may be increased to 2.0 mg a day. On Day 15, the child's dose may be increased to 2.5 mg a day. On Day 18, the child's dose may be increased to 3 mg a day. On Day 23, the child's dose may be increased to 3.5 mg a day.; PMT will include individual parent sessions held weekly for 9 weeks, with two booster sessions to be completed during the 3-month extension. Sessions will include development of problem-solving skills and behavior management strategies, practice activities, and role-playing with the behavioral therapist.; One pill will be taken once daily for the first 4 days and then twice daily until Week 21.
Other intervention name(s): Concerta; Risperdal; Community Parent Education Program
Intervention MeSH terms: Risperidone; Methylphenidate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Conduct Disorder; Attention Deficit and Disruptive Behavior Disorders