Clinical trial NCT02293655: The Effects of ADHD Medication (TEAM) Study
Official title: The Effects of ADHD Medication (TEAM) Study: Neurobehavioral Effects of Abrupt Methylphenidate Discontinuation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: ADHD
Keywords: ADHD
inattention
hyperactivity
methylphenidate
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Seattle Children's Hospital
First posted: 2014-11-18
Enrollment: 204
Sex: ALL
Minimum age (years): 7
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Parent ADHD Total Symptom Scores
timeFrame: baseline, study weeks 8, 9, 10, 12
measure: Inhibitory Control Reaction Time Variability (SD of the Reaction Time)
timeFrame: baseline, study weeks 8, 9, 10 & 12
measure: Math Computation - Number of Problems Completed Correctly
timeFrame: baseline, study weeks 8, 9, 10 & 12
measure: % Time on Task
timeFrame: baseline, study weeks 8, 9, 10, 12
Secondary outcomes:
measure: Barkley Sluggish Cognitive Tempo (SCT) Ratings
timeFrame: baseline, study weeks 8, 9, 10 &12
measure: Parent Ratings of Emotional Regulation
timeFrame: baseline, study weeks 8, 9, 10 &12
measure: Spatial Working Memory
timeFrame: baseline, study weeks 8, 9, 10 &12
measure: Math Reasoning
timeFrame: baseline, study weeks 1, 8, 9, 10 &12
measure: Reading Comprehension
timeFrame: baseline, study weeks 8, 9, 10 &12
measure: Written Expression
timeFrame: baseline, study weeks 1, 8, 9, 10 &12
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center
state: Ohio
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Tanya E. Froehlich, MD
role: PRINCIPAL_INVESTIGATOR
References: