Clinical trial NCT00183391: Stimulant Versus Nonstimulant Medication for Attention Deficit Hyperactivity Disorder in Children
Official title: Measuring and Predicting Response to Atomoxetine and Methylphenidate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Attention Deficit Disorder With Hyperactivity
Keywords: ADHD
Child
Adolescent
School
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2005-09-16
Enrollment: 232
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study will determine the effectiveness of stimulant and nonstimulant medication in treating the symptoms of attention deficit hyperactivity disorder (ADHD) in children and adolescents.

Detailed description: ADHD is one of the most frequently occurring disorders of children and adolescents and is a significant public health problem. The most common treatment for the condition is stimulant medication. However, there are an increasing number of children who are experiencing negative side effects from stimulants, such as dizziness, loss of appetite, and headaches; these side effects have made the need for alternative treatments all the more important. This study will compare the stimulant methylphenidate to the nonstimulant atomoxetine to determine which is more effective in treating ADHD symptoms in children and adolescents. The two medications differ in the neurotransmitters they influence. Stimulants such as methylphenidate act upon the neurotransmitter dopamine, while atomoxetine works on norepinephrine. It has been proposed that the difference in neurotransmitter stimulation may result in differences in an ADHD patient's response to treatment.

Participants will be randomly assigned to receive either methylphenidate or atomoxetine for between 4 to 6 weeks, depending on how soon they respond to the treatment. After the 4 to 6 week period, participants will be crossed-over to receive whichever medication they did not receive in the first part of the study.

Participants will have up to 14 weekly study visits. Over the first two visits, participants will undergo psychological and intelligence tests, a medical history, an electrocardiogram, blood and urine collection, and a physical exam. The remaining visits will occur weekly. During these visits, participants will receive their assigned medication and, along with their parents, will complete questionnaires about their response to treatment and any side effects they may be experiencing. The teachers of all participants will be asked to complete a questionnaire about their student's behavior at 4 different times during the study. Participant, parent, and teacher questionnaires will be used to assess the ADHD symptoms of participants, as well as self-report clinical scales completed by the participants.

Eligibility criteria: Inclusion Criteria:

* Meets DSM-IV-TR criteria for ADHD
* Scores at least 1.5 standard deviation higher than age and gender mean on ADHD-RS keyed to ADHD subtype
* CGI Severity ADHD Rating greater than or equal to 4
* Currently attends school with at least 3 months left in high school
* Currently lives at home with parent(s) or legal guardian(s), now and for the past year before study entry, and is expected to remain there
* Normal physical exam, laboratory tests, and electrocardiogram
* Pulse and blood pressure within 95% of age and gender mean
* Full Scale IQ is greater than or equal to 75 OR if the results of testing indicate that Full Scale IQ is not a good indicator of intellectual ability, a General Ability Index greater than or equal to 75
* Weight is between 20 and 85 kilograms
* Able to swallow pills
* Parent or guardian willing to provide informed consent

Exclusion Criteria:

* History of atomoxetine or methylphenidate intolerance
* Any existing medical condition for which study medications are contraindicated
* If the child is in psychotherapy, no changes in therapy expected during the study trial
* Presence of any of the following: autism, mental retardation, schizophrenia, a psychotic disorder, bipolar disorder, severe depression, or conduct disorder
* Presence of a comorbid disorder that should be the primary focus of treatment
* Presence of a medical or neurological disorder precluding study medications or assessing ADHD
* Allergic reactions to multiple medications
* History of alcohol or drug abuse in the 3 months before study entry, or positive urine toxic screen that is not explained by a time limited medical circumstance
* Involved in a medication treatment study in the 30 days before study entry
* Female who is sexually active and is unwilling to use birth control
* Evidence of child abuse or neglect

Primary outcomes:
measure: ADHD-RS Total Score
timeFrame: up to 14 weeks
Secondary outcomes:
measure: Treatment Preference Survey
timeFrame: Measured at ends of treatments one and two
measure: ADHD - H/I
timeFrame: up to 14 weeks
measure: ADHD-RS Inattention
timeFrame: up to 14 weeks
measure: Clinical Global Impressions (CGI)- Severity
timeFrame: up to 14 weeks
measure: Social Skills Rating Scale (SSRS)- Parent Version
timeFrame: up to 14 weeks
measure: Child Conflict Index (CCI)
timeFrame: up to 14 weeks
measure: Continuous Performance Test (CPT)
timeFrame: up to 14 weeks
measure: Children's Sleep Questionnaire
timeFrame: up to 14 weeks
measure: Assessment of Affective Range (AAR)
timeFrame: up to 14 weeks
measure: Tics: Total Motor
timeFrame: up to 14 weeks
measure: Tics: Total Phonic
timeFrame: up to 14 weeks
measure: Tics: Total Impairment
timeFrame: up to 14 weeks
measure: Vital Signs - Systolic Blood Pressure
timeFrame: up to 14 weeks
measure: Vital Signs - Diastolic Blood Pressure
timeFrame: up to 14 weeks
measure: Vital Signs - Pulse
timeFrame: up to 14 weeks
measure: SES (Hollingshead)
timeFrame: up to 14 weeks
measure: Conners-Wells Adolescent Self Report
timeFrame: up to 14 weeks
measure: Conners Teacher Rating Scale- Short
timeFrame: up to 14 weeks
measure: Child Behavior Checklist (CBCL)
timeFrame: Measured at screening
measure: Social Skills Rating Scale (SSRS)- Teacher Version
timeFrame: up to 14 weeks
measure: Permanent Mathematics Product Test (PERMP)
timeFrame: up to 14 weeks
measure: Actigraphy
timeFrame: Measured daily throughout the study
measure: Sleep Logs
timeFrame: Measured daily throughout the study
measure: Hyperactivity, Attention, and Learning Problems (HALP) Medical and Developmental History Questionnaire
timeFrame: Measured at screening
measure: HALP Rebound Effects Questionnaire
timeFrame: up to 14 weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois, Chicago - Institute for Juvenile Research
state: Illinois
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Jeffrey H. Newcorn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Illinois, Chicago - Institute for Juvenile Research
name: Mark A. Stein, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bedard AC, Stein MA, Halperin JM, Krone B, Rajwan E, Newcorn JH. Differential impact of methylphenidate and atomoxetine on sustained attention in youth with attention-deficit/hyperactivity disorder. J Child Psychol Psychiatry. 2015 Jan;56(1):40-8. doi: 10.1111/jcpp.12272. Epub 2014 Jun 19.
citation: Schulz KP, Bedard AV, Fan J, Hildebrandt TB, Stein MA, Ivanov I, Halperin JM, Newcorn JH. Striatal Activation Predicts Differential Therapeutic Responses to Methylphenidate and Atomoxetine. J Am Acad Child Adolesc Psychiatry. 2017 Jul;56(7):602-609.e2. doi: 10.1016/j.jaac.2017.04.005. Epub 2017 May 10.