- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02293655
The Effects of ADHD Medication (TEAM) Study (TEAM)
November 27, 2023 updated by: Children's Hospital Medical Center, Cincinnati
The Effects of ADHD Medication (TEAM) Study: Neurobehavioral Effects of Abrupt Methylphenidate Discontinuation
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.
Study Overview
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
Enrollment (Actual)
204
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ohio
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Cincinnati, Ohio, United States, 45229
- Children's Hospital Medical Center
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Washington
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Seattle, Washington, United States, 98105
- Seattle Children's Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
7 years to 11 years (Child)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- ADHD Diagnostic Status: Meets DSM-V criteria for ADHD, with Clinical Global Impression (CGI) rating corresponding to at least "moderately ill."
- 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
- 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:
- Psychiatric Medications: Current or prior use of any medication for psychological/psychiatric problems
- Behavioral Interventions: Current active participation in ADHD-related behavioral interventions, given that improvements due to these interventions may confound our group comparisons
- 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
- 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
- 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
- Pregnancy: The safety of MPH use during pregnancy has not been established
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: MPH Discontinuation
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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 Names:
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Active Comparator: Sustained MPH
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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 Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Parent ADHD Total Symptom Scores
Time Frame: baseline, study weeks 8, 9, 10, 12
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Parent Vanderbilt ADHD Rating Scale Total Symptom Score, minimum=0, maximum=54, higher scores indicate more/worse ADHD symptoms
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baseline, study weeks 8, 9, 10, 12
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Math Computation - Number of Problems Completed Correctly
Time Frame: baseline, study weeks 8, 9, 10 & 12
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Math Computation Curriculum-Based Measure - Number of Problems Completed Correctly.
Minimum=0, Maximum=600.
Higher scores indicate improved/better performance
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baseline, study weeks 8, 9, 10 & 12
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Inhibitory Control Reaction Time Variability (SD of the Reaction Time)
Time Frame: baseline, study weeks 8, 9, 10 & 12
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Assessed via the Go/No-Go computerized measure of inhibitory control reaction time variability (with standard deviation of the reaction time being the indicator variability variability).
Unit of measure is msec.
Minimum is 0, Maximum is 500.
Higher scores indicate more variability (higher standard deviation) in reaction time, indicating worse outcome (more characteristic of individuals with ADHD and less characteristic of typically developing individuals).
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baseline, study weeks 8, 9, 10 & 12
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% Time on Task
Time Frame: baseline, study weeks 8, 9, 10, 12
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Participants were videotaped while completing the 20-minute Analogue Math task.
Their behavior was coded in 20-second intervals by trained coders who determined if the children were on-task or off-task during each interval.
The amount of time coded as on-task was divided by the total amount of time and then multiplied by 100 to generate the % of time on task variable.
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baseline, study weeks 8, 9, 10, 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Barkley Sluggish Cognitive Tempo (SCT) Ratings
Time Frame: baseline, study weeks 8, 9, 10 &12
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assessed via parent-completed Barkley Sluggish Cognitive Tempo Scale.
Minimum=12, Max=48, higher scores indicate worse outcome.
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baseline, study weeks 8, 9, 10 &12
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Parent Ratings of Emotional Regulation
Time Frame: baseline, study weeks 8, 9, 10 &12
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assessed via parent-completed Emotion Regulation Checklist (ERC).
Outcome assessed is ERC total mean score: minimum value=1, max value=4, higher scores indicate worse outcome
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baseline, study weeks 8, 9, 10 &12
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Spatial Working Memory
Time Frame: baseline, study weeks 8, 9, 10 &12
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Spatial working memory was assessed via the Corsi Computerized Spatial Span Task, which requires the participant to reproduce a sequence of movements by tapping a series of blocks on a computer screen in the same order demonstrated by the examiner.
Outcome of interest is total trials correct.
Minimum score=0, max score=10.
Higher scores indicate better performance.
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baseline, study weeks 8, 9, 10 &12
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Math Reasoning
Time Frame: baseline, study weeks 1, 8, 9, 10 &12
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Math reasoning was assessed by child completion of the AIMSWEB curriculum based measure (CBM) test of Math Concepts and Applications.
At baseline (week 1), child's performance was assigned a value of 1.0.
The child's performance at weeks 8, 9, 10, and 12 was derived by dividing actual score on the test by the score predicted at that time point after applying the measure's normed "rate of improvement (ROI)" metric to the baseline score.
For example, a score of 1.5 at week 8 would indicate that the child's actual score at week 8 was 50% higher than the predicted score at week 8 (which was derived by applying the normed ROI metric to the baseline score).
Scores at weeks 8, 9, 10, 12 that are >1.0 indicate greater improvement than expected (so better outcome), while scores at weeks 8, 9, 10, 12 that are <1.0 indicate less improvement than expected (so worse outcome).
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baseline, study weeks 1, 8, 9, 10 &12
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Reading Comprehension
Time Frame: baseline, study weeks 8, 9, 10 &12
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Reading Comprehension was assessed by child completion of the AIMSWEB curriculum based measure (CBM) test of Reading Comprehension.
At baseline (week 1), child's performance was assigned a value of 1.0.
The child's performance at weeks 8, 9, 10, and 12 was derived by dividing actual score on the test by the score predicted at that time point after applying the measure's normed "rate of improvement (ROI)" metric to the baseline score.
For example, a score of 1.5 at week 8 would indicate that the child's actual score at week 8 was 50% higher than the predicted score at week 8 (which was derived by applying the normed ROI metric to the baseline score).
Scores at weeks 8, 9, 10, 12 that are >1.0 indicate greater improvement than expected (so better outcome), while scores at weeks 8, 9, 10, 12 that are <1.0 indicate less improvement than expected (so worse outcome).
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baseline, study weeks 8, 9, 10 &12
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Written Expression
Time Frame: baseline, study weeks 1, 8, 9, 10 &12
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Assessed by child completion of the AIMSWEB curriculum based measure (CBM) test of Written Expression, with the measure assessing number of words written by the child after receiving a prompt.
At baseline (week 1), child's performance was assigned a value of 1.0.
The child's performance at weeks 8, 9, 10, and 12 was derived by dividing actual score (# of words written) on the test by the score predicted at that time point after applying the measure's normed "rate of improvement (ROI)" metric to the baseline score.
For example, a score of 1.5 at week 8 would indicate that the child's actual score at week 8 was 50% higher than the predicted score at week 8 (which was derived by applying the normed ROI metric to the baseline score).
Scores at weeks 8, 9, 10, 12 that are >1.0 indicate greater improvement than expected (so better outcome), while scores at weeks 8, 9, 10, 12 that are <1.0 indicate less improvement than expected (so worse outcome).
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baseline, study weeks 1, 8, 9, 10 &12
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Tanya E. Froehlich, MD, Children's Hospital Medical Center, Cincinnati
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 12, 2015
Primary Completion (Actual)
June 30, 2020
Study Completion (Actual)
June 30, 2021
Study Registration Dates
First Submitted
October 29, 2014
First Submitted That Met QC Criteria
November 14, 2014
First Posted (Estimated)
November 18, 2014
Study Record Updates
Last Update Posted (Estimated)
December 21, 2023
Last Update Submitted That Met QC Criteria
November 27, 2023
Last Verified
November 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Attention Deficit and Disruptive Behavior Disorders
- Neurodevelopmental Disorders
- Attention Deficit Disorder with Hyperactivity
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Dopamine Agents
- Dopamine Uptake Inhibitors
- Central Nervous System Stimulants
- Methylphenidate
Other Study ID Numbers
- ADHDMedTEAMStudy
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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