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The Effects of ADHD Medication (TEAM) Study (TEAM)

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ClinicalTrials.gov Identifier: NCT02293655
Recruitment Status : Recruiting
First Posted : November 18, 2014
Last Update Posted : April 19, 2017
Sponsor:
Collaborator:
Seattle Children's Hospital
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Brief Summary:
This study evaluates the effects of receiving and then discontinuing methylphenidate (MPH) in children with ADHD. After receiving MPH for 8 weeks, participants will be randomized to either discontinue MPH (and receive placebo) OR remain on MPH for 4 weeks.

Condition or disease Intervention/treatment Phase
ADHD Drug: OROS-Methylphenidate (MPH) Phase 4

Detailed Description:
The stimulant methylphenidate (MPH) is the most commonly prescribed psychoactive medication in children. An abundance of studies attest to the efficacy of MPH for attenuating inattentive, hyperactive, and impulsive symptoms in children with ADHD. Despite its efficacy, most children with ADHD who are prescribed MPH have poor continuity of treatment for a variety of reasons, including forgetting to administer the medication and delays obtaining refills. In addition, it is an accepted clinical practice for physicians to omit MPH for periods of time, such as during the summer or on weekends (i.e., drug holidays). Since MPH discontinuation is considered to be benign, many clinicians do not employ any special procedures or inform families of any special precautions in regard to its cessation. However, increasing evidence suggests that the pharmacological effects of MPH cause lasting changes in brain neurochemistry that persist beyond medication discontinuation. Moreover, these neurobiological effects of discontinuation appear to have neurobehavioral consequences. There is a critical need to better understand the breadth and magnitude of the neurobehavioral effects caused by MPH discontinuation as well as to better understand the temporal trajectory of these deleterious effects. Hence, the primary goal of the proposed research is to conduct the first randomized, double-blind, placebo-controlled trial specifically designed to study the negative effects of MPH discontinuation at multiple time points. 180 children diagnosed with ADHD will participate across two recruitment sites. After undergoing a 4-week MPH titration trial and 4-week MPH maintenance phase, participants will be randomized to either discontinue MPH (and receive placebo) OR remain on MPH for 4 weeks. Comprehensive multi-time point, multi-informant (parents, teachers, study staff) and multi-modal (behavior/mood/affect ratings scales, direct behavior observations, standardized testing) assessments will be used to assess a broad range of neurobehavioral outcomes. We will examine the magnitude and time course of effects of MPH discontinuation on behavioral as well as cognitive and academic functioning in children with ADHD. Furthermore, we will examine moderators of the adverse effects of MPH discontinuation on these outcomes to aid in the identification of those who are at increased risk.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effects of ADHD Medication (TEAM) Study: Neurobehavioral Effects of Abrupt Methylphenidate Discontinuation
Study Start Date : January 2015
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: MPH Discontinuation
  1. Double-blind (DB) placebo-controlled 4-week methylphenidate (MPH) titration trial. Pts will receive 3 active dosages of MPH (children <25kg: 18mg, 27mg, 36mg; children >25kg: 18mg, 36mg, 54mg for) as well as 1 random week of placebo, given qAM. Pts will begin on the lowest dose (or a randomized placebo week) and proceed through all dose conditions in an incremental fashion.
  2. DB 4-week MPH maintenance phase. The clinician, parent, and teacher ratings of behavior and side effects from the titration trial weeks will be graphed. Two doctors will blindly review the graphs and judge which week was the optimal dose week. Pts will then receive their optimal dose of MPH (qAM) for 4 weeks.
  3. DB 4-week MPH Discontinuation Phase. Pts in this arm will receive placebo (qAM).
Drug: OROS-Methylphenidate (MPH)
OROS-methylphenidate will be taken orally once daily at doses that have been approved for the study age group by the U.S. FDA.
Other Name: Concerta

Active Comparator: Sustained MPH
  1. Double-blind (DB) placebo-controlled 4-week methylphenidate (MPH) titration trial. Pts will receive 3 active dosages of MPH (children <25kg: 18mg, 27mg, 36mg; children >25kg: 18mg, 36mg, 54mg for) as well as 1 random week of placebo, given qAM. Pts will begin on the lowest dose (or a randomized placebo week) and proceed through all dose conditions in an incremental fashion.
  2. DB 4-week MPH maintenance phase. The clinician, parent, and teacher ratings of behavior and side effects from the titration trial weeks will be graphed. Two doctors will blindly review the graphs and judge which week was the optimal dose week. Pts will then receive their optimal dose of MPH (qAM) for 4 weeks.
  3. DB 4-week MPH Discontinuation Phase. Pts in this arm will continue their optimal MPH dose (qAM).
Drug: OROS-Methylphenidate (MPH)
OROS-methylphenidate will be taken orally once daily at doses that have been approved for the study age group by the U.S. FDA.
Other Name: Concerta




Primary Outcome Measures :
  1. ADHD symptom scores [ Time Frame: baseline, study weeks 1, 2, 3, 4, 8, 9, 10 &12 ]
    Assessed via parent and teacher-completed Vanderbilt Rating Scales

  2. Off-task behavior [ Time Frame: baseline, study weeks 1, 8, 9, 10 & 12 ]
    Assessed by blinded raters during direct laboratory observations

  3. Inhibitory control reaction time variability [ Time Frame: baseline, study weeks 1, 8, 9, 10 & 12 ]
    Assessed via the Go/No-go computerized neuropsychological task

  4. Math computation [ Time Frame: baseline, study weeks 1, 8, 9, 10 & 12 ]
    Assessed via the AIMSWEB curriculum-based measurement


Secondary Outcome Measures :
  1. Sluggish cognitive tempo (SCT) ratings [ Time Frame: baseline, study weeks 1, 2, 3, 4, 8, 9, 10 &12 ]
    assessed via parent and teacher-completed Sluggish Cognitive Tempo Scale

  2. Executive function ratings [ Time Frame: baseline, study weeks 1, 8, 9, 10 &12 ]
    assessed via parent and teacher-completed Behavior Rating Inventory of Executive Function (BRIEF) scales

  3. Child ratings of depression [ Time Frame: baseline, study weeks 1, 8, 9, 10 &12 ]
    assessed via child-completed Children's Depression Inventory

  4. Child ratings of anxiety [ Time Frame: baseline, study weeks 1, 8, 9, 10 &12 ]
    assessed via child-completed Multidimensional Anxiety Scale for Children

  5. Child ratings of suicidality [ Time Frame: baseline, study weeks 1, 8, 9, 10 &12 ]
    assessed via child-completed Columbia Suicide Severity Rating Scale

  6. Parent ratings of emotional regulation [ Time Frame: baseline, study weeks 1, 8, 9, 10 &12 ]
    assessed via parent-completed Emotion Regulation Checklist

  7. Side effect ratings [ Time Frame: baseline, study weeks 1, 2, 3, 4, 8, 9, 10 &12 ]
    assessed via parent- and teacher-completed Pittsburgh Side Effects Rating Scale

  8. Sleep ratings [ Time Frame: baseline, study weeks 1, 8, 9, 10 &12 ]
    assessed via parent-completed Children's Sleep Habits Questionnaire

  9. Ecological Momentary Assessment [ Time Frame: Baseline, weeks 1, 8, and 9-12 ]
    Parent will complete daily ratings of behavior and mood (approx time to complete: 5 minutes each day) on a hand-held device during the specified weeks

  10. School observations [ Time Frame: baseline, study weeks 1, 8, 9, 10 &12 ]
    Trained observers will visit the child's school and rate child behavior using the Classroom Observation Code. During a scheduled observation period, the target child will be observed for four 4 minute blocks, divided into 16 continuous 15 second intervals, yielding 8 minutes of data on each child.

  11. Spatial working memory [ Time Frame: baseline, study weeks 1, 8, 9, 10 &12 ]
    Assessed via the Computerized Spatial Span Task

  12. Math reasoning [ Time Frame: baseline, study weeks 1, 8, 9, 10 &12 ]
    Assessed by child's completion of the AIMSWEB CBM test of math concepts and applications

  13. Reading fluency and comprehension [ Time Frame: baseline, study weeks 1, 8, 9, 10 &12 ]
    Assessed by child's completion of the AIMSWEB CBM test of reading fluency and comprehension

  14. Written expression [ Time Frame: baseline, study weeks 1, 8, 9, 10 &12 ]
    Assessed by child's completion of the AIMSWEB CBM test of written expression

  15. Spelling [ Time Frame: baseline, study weeks 1, 8, 9, 10 &12 ]
    Assessed by child's completion of the AIMSWEB CBM test of spelling.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   7 Years to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. ADHD Diagnostic Status: Meets DSM-V criteria for ADHD, with Clinical Global Impression (CGI) rating corresponding to at least "moderately ill."
  2. Cognitive and Academic Functioning: Intelligence Quotient (IQ) of >80 as estimated by Vocabulary and Block Design subtests of the Wechsler Intelligence Scale for Children-4th Edition and scaled scores >80 on the Wechsler Individual Achievement Test-2nd edition Reading and Math subtests
  3. Physical Health: Physical exam and ECG findings are judged to be normal for age and sex by study physician and/or medical consultant, and there is no co-existing condition for which MPH is contraindicated 4. School: Enrolled in a school setting rather than a home-school program. This ensures that we can obtain parent and teacher ratings from separate individuals for diagnosis and outcome assessment

Exclusion Criteria:

  1. Psychiatric Medications: Current or prior use of any medication for psychological/psychiatric problems
  2. Behavioral Interventions: Current active participation in ADHD-related behavioral interventions, given that improvements due to these interventions may confound our group comparisons
  3. Psychiatric or Neurobehavioral Conditions: Children with mania/hypomania, schizophrenia, or severe depressive disorder, as determined by the K-SADS, will be excluded since ADHD medications may not be an appropriate first line of treatment for children with these comorbid disorders
  4. Organic Brain Injury: History of head trauma, neurological disorder (including epilepsy), or other disorder affecting brain function due to potential differences in neurophysiology of ADHD phenotype
  5. Cardiovascular Risk Factors: Children with a personal history or family history of cardiovascular risk factors will be excluded, or given the option of participating in the study after obtaining an EKG and verification from a pediatric cardiologist regarding the safety of their participation in a trial of methylphenidate. In this case, families will be responsible for the costs of EKG and any necessary cardiologist evaluation
  6. Pregnancy: The safety of MPH use during pregnancy has not been established

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): NCT02293655


Contacts
Contact: Tanya E. Froehlich, MD 513-636-1154 tanya.froehlich@cchmc.org
Contact: Mark A Stein, PhD 206-987-2164 Mark.Stein@seattlechildrens.org

Locations
United States, Ohio
Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Tanya E. Froehlich, MD    513-636-1154    tanya.froehlich@cchmc.org   
United States, Washington
Seattle Children's Hospital Not yet recruiting
Seattle, Washington, United States, 98105
Contact: Mark A. Stein, PhD    206-987-2164    Mark.Stein@seattlechildrens.org   
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Seattle Children's Hospital
Investigators
Principal Investigator: Tanya E. Froehlich, MD Children's Hospital Medical Center, Cincinnati

Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT02293655     History of Changes
Other Study ID Numbers: ADHDMedTEAMStudy
First Posted: November 18, 2014    Key Record Dates
Last Update Posted: April 19, 2017
Last Verified: April 2017

Keywords provided by Children's Hospital Medical Center, Cincinnati:
ADHD
inattention
hyperactivity
methylphenidate

Additional relevant MeSH terms:
Methylphenidate
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