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Stimulant Versus Nonstimulant Medication for Attention Deficit Hyperactivity Disorder in Children

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ClinicalTrials.gov Identifier: NCT00183391
Recruitment Status : Completed
First Posted : September 16, 2005
Results First Posted : June 6, 2018
Last Update Posted : June 6, 2018
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Jeffrey Newcorn, Icahn School of Medicine at Mount Sinai

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.

Condition or disease Intervention/treatment Phase
Attention Deficit Disorder With Hyperactivity Drug: Atomoxetine Drug: Methylphenidate Phase 4

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 232 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Measuring and Predicting Response to Atomoxetine and Methylphenidate
Study Start Date : July 2005
Actual Primary Completion Date : June 2011
Actual Study Completion Date : June 2011


Arm Intervention/treatment
Active Comparator: Atomoxetine
Participants will receive treatment for ADHD with the non-stimulant atomoxetine
Drug: Atomoxetine
Participants will be randomly assigned to receive either methylphenidate or atomoxetine for either 2 or 5 weeks, depending on how soon they respond to the treatment. After the 2- or 5-week period, participants will be crossed-over to receive whichever medication they did not receive in the first part of the study.

Drug: Methylphenidate
Participants will be randomly assigned to receive either methylphenidate or atomoxetine for either 2 or 5 weeks, depending on how soon they respond to the treatment. After the 2- or 5-week period, participants will be crossed-over to receive whichever medication they did not receive in the first part of the study.

Active Comparator: Methylphenidate
Participants will receive treatment for ADHD with the stimulant methylphenidate
Drug: Atomoxetine
Participants will be randomly assigned to receive either methylphenidate or atomoxetine for either 2 or 5 weeks, depending on how soon they respond to the treatment. After the 2- or 5-week period, participants will be crossed-over to receive whichever medication they did not receive in the first part of the study.

Drug: Methylphenidate
Participants will be randomly assigned to receive either methylphenidate or atomoxetine for either 2 or 5 weeks, depending on how soon they respond to the treatment. After the 2- or 5-week period, participants will be crossed-over to receive whichever medication they did not receive in the first part of the study.




Primary Outcome Measures :
  1. ADHD-RS Total Score [ Time Frame: up to 14 weeks ]
    ADHD-RS Total Score Attention Deficit Hyperactivity Disorder Rating Scale. Each item on the 18-item measure is scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms), yielding a possible total score of 0-54. Higher score indicates higher probability of diagnosis.


Secondary Outcome Measures :
  1. Treatment Preference Survey [ Time Frame: Measured at ends of treatments one and two ]
  2. ADHD - H/I [ Time Frame: up to 14 weeks ]
    Attention deficit/hyperactivity disorder - hyperactivity/impulsivity (ADHD- H/I). Each item on the 18-item measure is scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms), yielding a possible total score of 0-27. Higher score indicates higher probability of diagnosis.

  3. ADHD-RS Inattention [ Time Frame: up to 14 weeks ]
    Each item on the 18-item measure is scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms), yielding a possible total score of 0-27. Higher score indicates higher probability of diagnosis.

  4. Clinical Global Impressions (CGI)- Severity [ Time Frame: up to 14 weeks ]
    The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.

  5. Social Skills Rating Scale (SSRS)- Parent Version [ Time Frame: up to 14 weeks ]
    Measure of social skills, higher score is better. This scale is based on t-scores and does not have psychometrics available.

  6. Child Conflict Index (CCI) [ Time Frame: up to 14 weeks ]
    Measure of conflict within the home over the past 24 hours. The CCI is a validated measure of family conflicts in the home and is completed by parents. It consists of 42 items (for boys) or 36 items (for girls) reflecting attention-seeking and conflictual behavior, as well as negativity and withdrawal. Items are scored as yes (1 point) or no (0 points). Mean score between 0 and 1 reported, with higher score indicating greater conflict.

  7. Continuous Performance Test (CPT) [ Time Frame: up to 14 weeks ]
    CPT Commissions, impulsive responses, higher score is worse. This scale is based on t-scores and does not have psychometrics available.

  8. Children's Sleep Questionnaire [ Time Frame: up to 14 weeks ]
    Children's Sleep Problems Severity, sum of scores, higher is worse.The scale assessed contains 16 items, each scored 0 to 3, with 0 representing no problems and 3 representing daily problems. total range from 0 to 48. This score does not have psychometrics available.

  9. Assessment of Affective Range (AAR) [ Time Frame: up to 14 weeks ]
    Affective problems. This scale consists of 8 items, scored 0-3, with 0 representing no problems and 3 representing extreme problems. This analysis presents sum of scores, higher is worse. Full range from 0 to 24. This score does not have psychometrics available.

  10. Tics: Total Motor [ Time Frame: up to 14 weeks ]
    Modified Yale Global Tic Severity Scale, sum, higher is worse. This score does not have psychometrics available. The Yale Global Tic Severity Scale (YGTSS) is a semistructured clinician-rated instrument that assesses the severity and frequency of motor and phonic tics over the previous week. Five index scores are obtained during the assessment, where higher scores indicate greater frequency or severity. These indices are: Total Motor Tic Score (0-25), Total Phonic Tic Score (0-25), Total Tic Score (0-50) Overall Impairment Rating (0-50).

  11. Tics: Total Phonic [ Time Frame: up to 14 weeks ]
    Modified Yale Global Tic Severity Scale, sum, higher is worse. This score does not have psychometrics available. The Yale Global Tic Severity Scale (YGTSS) is a semistructured clinician-rated instrument that assesses the severity and frequency of motor and phonic tics over the previous week. Five index scores are obtained during the assessment, where higher scores indicate greater frequency or severity. These indices are: Total Motor Tic Score (0-25), Total Phonic Tic Score (0-25), Total Tic Score (0-50) Overall Impairment Rating (0-50).

  12. Tics: Total Impairment [ Time Frame: up to 14 weeks ]
    Modified Yale Global Tic Severity Scale, sum, higher is worse. This score does not have psychometrics available. The Yale Global Tic Severity Scale (YGTSS) is a semistructured clinician-rated instrument that assesses the severity and frequency of motor and phonic tics over the previous week. Five index scores are obtained during the assessment, where higher scores indicate greater frequency or severity. These indices are: Total Motor Tic Score (0-25), Total Phonic Tic Score (0-25), Total Tic Score (0-50) Overall Impairment Rating (0-50).

  13. Vital Signs - Systolic Blood Pressure [ Time Frame: up to 14 weeks ]
    Systolic blood pressure - the amount of pressure in arteries during contraction of the heart muscle Normal range varies by age, sex, height and weight and can range from 80mm Hg to 130mmHg

  14. Vital Signs - Diastolic Blood Pressure [ Time Frame: up to 14 weeks ]
    Diastole blood pressure - blood pressure when the heart muscle is between beats. normal range varies by age, sex, height and weight and can range from 34mm Hg to 90mmHg

  15. Vital Signs - Pulse [ Time Frame: up to 14 weeks ]
    Heartbeats per minute. Range varies from 50-205 depending on age and level of activity.

  16. SES (Hollingshead) [ Time Frame: up to 14 weeks ]
    Measure of socioeconomic status, score calculated from averaging likert responses, lower = worse

  17. Conners-Wells Adolescent Self Report [ Time Frame: up to 14 weeks ]
    Standardized measure of ADHD symptoms and severity, norm referenced T scores, higher = worse

  18. Conners Teacher Rating Scale- Short [ Time Frame: up to 14 weeks ]
    Standardized measure of ADHD symptoms and severity, norm referenced T scores, higher = worse

  19. Child Behavior Checklist (CBCL) [ Time Frame: Measured at screening ]
    CBCL Total Score, measure of psychosocial problems, higher is worse.

  20. Social Skills Rating Scale (SSRS)- Teacher Version [ Time Frame: up to 14 weeks ]
    Measure of social skills, higher score is better. This scale is based on t-scores and does not have psychometrics available.

  21. Permanent Mathematics Product Test (PERMP) [ Time Frame: up to 14 weeks ]
    Measure of fluency in performance of simple mathematics, sum, lower = worse

  22. Actigraphy [ Time Frame: Measured daily throughout the study ]
    Measure of physical activity

  23. Sleep Logs [ Time Frame: Measured daily throughout the study ]
    Questionnaire, qualitative

  24. Hyperactivity, Attention, and Learning Problems (HALP) Medical and Developmental History Questionnaire [ Time Frame: Measured at screening ]
    Questionnaire, qualitative designed to collect family history, prenatal environmental influences, and developmental history.

  25. HALP Rebound Effects Questionnaire [ Time Frame: up to 14 weeks ]
    Questionnaire, qualitative assesses symptoms of rebound (moodiness, irritability, aggression, and ADHD symptoms) when the medication wears off at night.



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Ages Eligible for Study:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00183391


Locations
United States, Illinois
University of Illinois, Chicago - Institute for Juvenile Research
Chicago, Illinois, United States, 60612
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Jeffrey H. Newcorn, MD Icahn School of Medicine at Mount Sinai
Principal Investigator: Mark A. Stein, PhD University of Illinois, Chicago - Institute for Juvenile Research

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jeffrey Newcorn, Associate Professor, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT00183391     History of Changes
Other Study ID Numbers: GCO 03-0612-00002
R01MH070935 ( U.S. NIH Grant/Contract )
R01MH070564 ( U.S. NIH Grant/Contract )
DSIR 84-CTM
First Posted: September 16, 2005    Key Record Dates
Results First Posted: June 6, 2018
Last Update Posted: June 6, 2018
Last Verified: May 2018

Keywords provided by Jeffrey Newcorn, Icahn School of Medicine at Mount Sinai:
ADHD
Child
Adolescent
School

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Hyperkinesis
Attention Deficit and Disruptive Behavior Disorders
Neurodevelopmental Disorders
Mental Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Methylphenidate
Atomoxetine Hydrochloride
Central Nervous System Stimulants
Physiological Effects of Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Adrenergic Uptake Inhibitors
Adrenergic Agents