ADHD
Conditions
Keywords
ADHD, inattention, hyperactivity, methylphenidate
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.
Interventions
DRUGOROS-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.
Sponsors
Seattle Children's Hospital
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
7 Years to 11 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parent ADHD Total Symptom Scores | baseline, study weeks 8, 9, 10, 12 | Parent Vanderbilt ADHD Rating Scale Total Symptom Score, minimum=0, maximum=54, higher scores indicate more/worse ADHD symptoms |
| Inhibitory Control Reaction Time Variability (SD of the Reaction Time) | baseline, study weeks 8, 9, 10 & 12 | 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). |
| Math Computation - Number of Problems Completed Correctly | baseline, study weeks 8, 9, 10 & 12 | Math Computation Curriculum-Based Measure - Number of Problems Completed Correctly. Minimum=0, Maximum=600. Higher scores indicate improved/better performance |
| % Time on Task | baseline, study weeks 8, 9, 10, 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reading Comprehension | baseline, study weeks 8, 9, 10 &12 | 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). |
| Barkley Sluggish Cognitive Tempo (SCT) Ratings | baseline, study weeks 8, 9, 10 &12 | assessed via parent-completed Barkley Sluggish Cognitive Tempo Scale. Minimum=12, Max=48, higher scores indicate worse outcome. |
| Written Expression | baseline, study weeks 1, 8, 9, 10 &12 | 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). |
| Parent Ratings of Emotional Regulation | baseline, study weeks 8, 9, 10 &12 | 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 |
| Spatial Working Memory | baseline, study weeks 8, 9, 10 &12 | 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. |
| Math Reasoning | baseline, study weeks 1, 8, 9, 10 &12 | 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). |
Countries
United States
Participant flow
Recruitment details
The number Enrolled (those who signed informed consent) differs from the number who Started in the Participant Flow module because: 1) some children who signed informed consent were determined to be ineligible after having formal assessment for study inclusion, 2) some children were unable to learn to swallow the study pill so could not start protocol participation, 3) some families changed their minds about participating after signing informed consent but before starting study procedures.
Participants by arm
| Arm | Count |
|---|---|
| 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).
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. | 92 |
| 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).
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. | 17 |
| Total | 109 |
Baseline characteristics
| Characteristic | MPH Discontinuation | Total | Sustained MPH |
|---|---|---|---|
| Age, Categorical <=18 years | 92 Participants | 109 Participants | 17 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 9 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 84 Participants | 100 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Parent Vanderbilt ADHD Total Symptom Score | 36.2 score on a scale STANDARD_DEVIATION 8.3 | 36.0 score on a scale STANDARD_DEVIATION 8.7 | 34.6 score on a scale STANDARD_DEVIATION 10.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 8 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 10 Participants | 10 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 73 Participants | 88 Participants | 15 Participants |
| Region of Enrollment United States | 92 participants | 109 participants | 17 participants |
| Sex: Female, Male Female | 31 Participants | 37 Participants | 6 Participants |
| Sex: Female, Male Male | 61 Participants | 72 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 92 | 0 / 17 |
| other Total, other adverse events | 55 / 92 | 15 / 17 |
| serious Total, serious adverse events | 1 / 92 | 0 / 17 |
Outcome results
Primary
Inhibitory Control Reaction Time Variability (SD of the Reaction Time)
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).
Time frame: baseline, study weeks 8, 9, 10 & 12
Population: There was some attrition and missing data at different data collection points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MPH Discontinuation | Inhibitory Control Reaction Time Variability (SD of the Reaction Time) | Maintenance Visit (week 8) | 195.9 msec | Standard Error 17.1 |
| MPH Discontinuation | Inhibitory Control Reaction Time Variability (SD of the Reaction Time) | Randomization 2 (week 10) | 288.2 msec | Standard Error 19.3 |
| MPH Discontinuation | Inhibitory Control Reaction Time Variability (SD of the Reaction Time) | Randomization 1 (week 9) | 250.8 msec | Standard Error 18.8 |
| MPH Discontinuation | Inhibitory Control Reaction Time Variability (SD of the Reaction Time) | Randomization 3 (week 12) | 285.2 msec | Standard Error 20.3 |
| MPH Discontinuation | Inhibitory Control Reaction Time Variability (SD of the Reaction Time) | Baseline | 219.6 msec | Standard Error 17.8 |
| Sustained MPH | Inhibitory Control Reaction Time Variability (SD of the Reaction Time) | Randomization 3 (week 12) | 199.8 msec | Standard Error 36 |
| Sustained MPH | Inhibitory Control Reaction Time Variability (SD of the Reaction Time) | Baseline | 196.0 msec | Standard Error 27.9 |
| Sustained MPH | Inhibitory Control Reaction Time Variability (SD of the Reaction Time) | Maintenance Visit (week 8) | 199.6 msec | Standard Error 31.5 |
| Sustained MPH | Inhibitory Control Reaction Time Variability (SD of the Reaction Time) | Randomization 1 (week 9) | 183.8 msec | Standard Error 37.1 |
| Sustained MPH | Inhibitory Control Reaction Time Variability (SD of the Reaction Time) | Randomization 2 (week 10) | 228.5 msec | Standard Error 52.8 |
Comparison: Compared at baseline timepointp-value: 0.32t-test, 2 sided
Comparison: Compared at Maintenance Time Point (week 8)p-value: 0.9t-test, 2 sided
Comparison: Compared at Randomization Phase 1 (week 9)p-value: 0.007t-test, 2 sided
Comparison: Compared at Randomization Phase 2 (week 10)p-value: 0.26t-test, 2 sided
Comparison: Compared at Randomization Phase 3 (week 12)p-value: 0.01t-test, 2 sided
Primary
Math Computation - Number of Problems Completed Correctly
Math Computation Curriculum-Based Measure - Number of Problems Completed Correctly. Minimum=0, Maximum=600. Higher scores indicate improved/better performance
Time frame: baseline, study weeks 8, 9, 10 & 12
Population: There was some attrition and missing data at different data collection points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MPH Discontinuation | Math Computation - Number of Problems Completed Correctly | Maintenance Visit (week 8) | 264.71 Number of problems completed correctly | Standard Deviation 157.4 |
| MPH Discontinuation | Math Computation - Number of Problems Completed Correctly | Randomization 2 (week 10) | 201.69 Number of problems completed correctly | Standard Deviation 164.3 |
| MPH Discontinuation | Math Computation - Number of Problems Completed Correctly | Randomization 1 (week 9) | 221.19 Number of problems completed correctly | Standard Deviation 175.3 |
| MPH Discontinuation | Math Computation - Number of Problems Completed Correctly | Randomization 3 (week 12) | 201.10 Number of problems completed correctly | Standard Deviation 180.3 |
| MPH Discontinuation | Math Computation - Number of Problems Completed Correctly | Baseline | 200.84 Number of problems completed correctly | Standard Deviation 152.8 |
| Sustained MPH | Math Computation - Number of Problems Completed Correctly | Randomization 3 (week 12) | 277.51 Number of problems completed correctly | Standard Deviation 190 |
| Sustained MPH | Math Computation - Number of Problems Completed Correctly | Baseline | 230.93 Number of problems completed correctly | Standard Deviation 127.3 |
| Sustained MPH | Math Computation - Number of Problems Completed Correctly | Maintenance Visit (week 8) | 320.12 Number of problems completed correctly | Standard Deviation 142.3 |
| Sustained MPH | Math Computation - Number of Problems Completed Correctly | Randomization 1 (week 9) | 333.50 Number of problems completed correctly | Standard Deviation 214.1 |
| Sustained MPH | Math Computation - Number of Problems Completed Correctly | Randomization 2 (week 10) | 323.25 Number of problems completed correctly | Standard Deviation 203.6 |
Comparison: Comparison at Baselinep-value: 0.33t-test, 2 sided
Comparison: Comparison at Maintenance (week 8)p-value: 0.06t-test, 2 sided
Comparison: Comparison at Randomization Phase 1 (week 9)p-value: 0.05t-test, 2 sided
Comparison: Comparison at Randomization Phase 2 (week 10)p-value: 0.008t-test, 2 sided
Comparison: Comparison at Randomization Phase 3 (week 12)p-value: 0.07t-test, 2 sided
Primary
Parent ADHD Total Symptom Scores
Parent Vanderbilt ADHD Rating Scale Total Symptom Score, minimum=0, maximum=54, higher scores indicate more/worse ADHD symptoms
Time frame: baseline, study weeks 8, 9, 10, 12
Population: There was some attrition and missing data at different data collection points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MPH Discontinuation | Parent ADHD Total Symptom Scores | Maintenance Visit (week 8) | 17.6 score on a scale | Standard Deviation 8.8 |
| MPH Discontinuation | Parent ADHD Total Symptom Scores | Randomization 2 (week 10) | 23.8 score on a scale | Standard Deviation 11.6 |
| MPH Discontinuation | Parent ADHD Total Symptom Scores | Randomization 1 (week 9) | 16.5 score on a scale | Standard Deviation 12 |
| MPH Discontinuation | Parent ADHD Total Symptom Scores | Randomization 3 (week 12) | 25.2 score on a scale | Standard Deviation 11.6 |
| MPH Discontinuation | Parent ADHD Total Symptom Scores | Baseline | 36.2 score on a scale | Standard Deviation 8.3 |
| Sustained MPH | Parent ADHD Total Symptom Scores | Randomization 3 (week 12) | 17.3 score on a scale | Standard Deviation 12.3 |
| Sustained MPH | Parent ADHD Total Symptom Scores | Baseline | 34.6 score on a scale | Standard Deviation 10.9 |
| Sustained MPH | Parent ADHD Total Symptom Scores | Maintenance Visit (week 8) | 15.3 score on a scale | Standard Deviation 8.3 |
| Sustained MPH | Parent ADHD Total Symptom Scores | Randomization 1 (week 9) | 12.3 score on a scale | Standard Deviation 10.4 |
| Sustained MPH | Parent ADHD Total Symptom Scores | Randomization 2 (week 10) | 14.3 score on a scale | Standard Deviation 8.3 |
Comparison: Compared at Baseline Time pointp-value: 0.55t-test, 2 sided
Comparison: Comparison at MPH Maintenance Visit (Week 8)p-value: 0.3t-test, 2 sided
Comparison: Comparison at Randomization Phase 1 (Week 9)p-value: 0.28t-test, 2 sided
Comparison: Comparison at Randomization Phase 2 (Week 10)p-value: 0t-test, 2 sided
Comparison: Comparison at Randomization Phase 3 (Week 12)p-value: 0.01t-test, 2 sided
Primary
% Time on Task
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.
Time frame: baseline, study weeks 8, 9, 10, 12
Population: There was some attrition and missing data at different data collection points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MPH Discontinuation | % Time on Task | Week 8 (MPH Maintenance dose) | 83.9 percentage of time spent on task | Standard Error 3.8 |
| MPH Discontinuation | % Time on Task | Week 10 | 69.5 percentage of time spent on task | Standard Error 4.2 |
| MPH Discontinuation | % Time on Task | Week 9 | 73.1 percentage of time spent on task | Standard Error 3.6 |
| MPH Discontinuation | % Time on Task | Week 12 | 66.6 percentage of time spent on task | Standard Error 4.5 |
| MPH Discontinuation | % Time on Task | Baseline | 74.4 percentage of time spent on task | Standard Error 4.2 |
| Sustained MPH | % Time on Task | Week 12 | 82.6 percentage of time spent on task | Standard Error 6.5 |
| Sustained MPH | % Time on Task | Baseline | 85.2 percentage of time spent on task | Standard Error 6.4 |
| Sustained MPH | % Time on Task | Week 8 (MPH Maintenance dose) | 92.7 percentage of time spent on task | Standard Error 3.9 |
| Sustained MPH | % Time on Task | Week 9 | 91.5 percentage of time spent on task | Standard Error 4.3 |
| Sustained MPH | % Time on Task | Week 10 | 89.2 percentage of time spent on task | Standard Error 4.2 |
Secondary
Barkley Sluggish Cognitive Tempo (SCT) Ratings
assessed via parent-completed Barkley Sluggish Cognitive Tempo Scale. Minimum=12, Max=48, higher scores indicate worse outcome.
Time frame: baseline, study weeks 8, 9, 10 &12
Population: Note: There was some missing data as well as attrition. the numbers of participants with available data for this outcome has been verified.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MPH Discontinuation | Barkley Sluggish Cognitive Tempo (SCT) Ratings | Maintenance (week 8) | 18.5 score on a scale | Standard Error 1.1 |
| MPH Discontinuation | Barkley Sluggish Cognitive Tempo (SCT) Ratings | Randomization 2 (week 10) | 18.7 score on a scale | Standard Error 1.1 |
| MPH Discontinuation | Barkley Sluggish Cognitive Tempo (SCT) Ratings | Randomization 1 (week 9) | 18.4 score on a scale | Standard Error 1.2 |
| MPH Discontinuation | Barkley Sluggish Cognitive Tempo (SCT) Ratings | Randomization 3 (week 12) | 18.8 score on a scale | Standard Error 1.1 |
| MPH Discontinuation | Barkley Sluggish Cognitive Tempo (SCT) Ratings | Baseline (week 1) | 24.41 score on a scale | Standard Error 1.26 |
| Sustained MPH | Barkley Sluggish Cognitive Tempo (SCT) Ratings | Randomization 3 (week 12) | 17.6 score on a scale | Standard Error 1 |
| Sustained MPH | Barkley Sluggish Cognitive Tempo (SCT) Ratings | Baseline (week 1) | 24.19 score on a scale | Standard Error 1.33 |
| Sustained MPH | Barkley Sluggish Cognitive Tempo (SCT) Ratings | Maintenance (week 8) | 18.2 score on a scale | Standard Error 1 |
| Sustained MPH | Barkley Sluggish Cognitive Tempo (SCT) Ratings | Randomization 1 (week 9) | 17.5 score on a scale | Standard Error 1.3 |
| Sustained MPH | Barkley Sluggish Cognitive Tempo (SCT) Ratings | Randomization 2 (week 10) | 18.0 score on a scale | Standard Error 1.1 |
Secondary
Math Reasoning
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).
Time frame: baseline, study weeks 1, 8, 9, 10 &12
Population: some missing data due to factors such as attrition and the test not being appropriate to administer all grade levels (e.g., not designed for participants who were in 1st grade) grade. # of participants with available data has been verified.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MPH Discontinuation | Math Reasoning | Week 8 | 1.09 percentage of expected improvement | Standard Error 0.06 |
| MPH Discontinuation | Math Reasoning | week 10 | 1.15 percentage of expected improvement | Standard Error 0.07 |
| MPH Discontinuation | Math Reasoning | week 9 | 1.11 percentage of expected improvement | Standard Error 0.62 |
| MPH Discontinuation | Math Reasoning | week 12 | 1.10 percentage of expected improvement | Standard Error 0.06 |
| MPH Discontinuation | Math Reasoning | Baseline | 1.0 percentage of expected improvement | Standard Error 0 |
| Sustained MPH | Math Reasoning | week 12 | 1.65 percentage of expected improvement | Standard Error 0.16 |
| Sustained MPH | Math Reasoning | Baseline | 1.0 percentage of expected improvement | Standard Error 0 |
| Sustained MPH | Math Reasoning | Week 8 | 1.27 percentage of expected improvement | Standard Error 0.08 |
| Sustained MPH | Math Reasoning | week 9 | 1.50 percentage of expected improvement | Standard Error 0.15 |
| Sustained MPH | Math Reasoning | week 10 | 1.50 percentage of expected improvement | Standard Error 0.13 |
Secondary
Parent Ratings of Emotional Regulation
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
Time frame: baseline, study weeks 8, 9, 10 &12
Population: There was some attrition and some missing data. # of participants with available data has been verified.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MPH Discontinuation | Parent Ratings of Emotional Regulation | Randomization 1 (wk 9) | 1.8 score on a scale | Standard Error 0.2 |
| MPH Discontinuation | Parent Ratings of Emotional Regulation | Maintenance (wk 8) | 1.8 score on a scale | Standard Error 0.1 |
| MPH Discontinuation | Parent Ratings of Emotional Regulation | Randomization 2 (wk 10) | 1.9 score on a scale | Standard Error 0.1 |
| MPH Discontinuation | Parent Ratings of Emotional Regulation | Randomization 3 (wk 12) | 1.9 score on a scale | Standard Error 0.1 |
| MPH Discontinuation | Parent Ratings of Emotional Regulation | Baseline | 2.1 score on a scale | Standard Error 0.1 |
| Sustained MPH | Parent Ratings of Emotional Regulation | Randomization 3 (wk 12) | 1.8 score on a scale | Standard Error 0.1 |
| Sustained MPH | Parent Ratings of Emotional Regulation | Baseline | 2.1 score on a scale | Standard Error 0.2 |
| Sustained MPH | Parent Ratings of Emotional Regulation | Maintenance (wk 8) | 1.8 score on a scale | Standard Error 0.1 |
| Sustained MPH | Parent Ratings of Emotional Regulation | Randomization 1 (wk 9) | 1.7 score on a scale | Standard Error 0.1 |
| Sustained MPH | Parent Ratings of Emotional Regulation | Randomization 2 (wk 10) | 1.8 score on a scale | Standard Error 0.1 |
Secondary
Reading Comprehension
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).
Time frame: baseline, study weeks 8, 9, 10 &12
Population: some missing data due to attrition, non-valid test administration. Numbers of participants with available data has been verified.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MPH Discontinuation | Reading Comprehension | week 8 | 1.00 percentage of expected improvement | Standard Error 0.05 |
| MPH Discontinuation | Reading Comprehension | week 10 | 1.12 percentage of expected improvement | Standard Error 0.05 |
| MPH Discontinuation | Reading Comprehension | week 9 | 1.02 percentage of expected improvement | Standard Error 0.05 |
| MPH Discontinuation | Reading Comprehension | week 12 | 1.01 percentage of expected improvement | Standard Error 0.06 |
| MPH Discontinuation | Reading Comprehension | baseline | 1.00 percentage of expected improvement | Standard Error 0 |
| Sustained MPH | Reading Comprehension | week 12 | 1.29 percentage of expected improvement | Standard Error 0.14 |
| Sustained MPH | Reading Comprehension | baseline | 1.00 percentage of expected improvement | Standard Error 0 |
| Sustained MPH | Reading Comprehension | week 8 | 0.99 percentage of expected improvement | Standard Error 0.11 |
| Sustained MPH | Reading Comprehension | week 9 | 1.25 percentage of expected improvement | Standard Error 0.18 |
| Sustained MPH | Reading Comprehension | week 10 | 1.27 percentage of expected improvement | Standard Error 0.11 |
Secondary
Spatial Working Memory
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.
Time frame: baseline, study weeks 8, 9, 10 &12
Population: some missing data due to attrition, non-valid trials/responses, and equipment failure. # of participants with available data has been verified.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MPH Discontinuation | Spatial Working Memory | Week 8 (med maintenance) | 6.46 total number of correct trials | Standard Error 0.25 |
| MPH Discontinuation | Spatial Working Memory | week 10 | 6.54 total number of correct trials | Standard Error 0.28 |
| MPH Discontinuation | Spatial Working Memory | week 9 | 6.67 total number of correct trials | Standard Error 0.25 |
| MPH Discontinuation | Spatial Working Memory | week 12 | 6.48 total number of correct trials | Standard Error 0.29 |
| MPH Discontinuation | Spatial Working Memory | Baseline | 6.43 total number of correct trials | Standard Error 0.27 |
| Sustained MPH | Spatial Working Memory | week 12 | 7.24 total number of correct trials | Standard Error 0.45 |
| Sustained MPH | Spatial Working Memory | Baseline | 6.83 total number of correct trials | Standard Error 0.33 |
| Sustained MPH | Spatial Working Memory | Week 8 (med maintenance) | 6.63 total number of correct trials | Standard Error 0.4 |
| Sustained MPH | Spatial Working Memory | week 9 | 7.42 total number of correct trials | Standard Error 0.42 |
| Sustained MPH | Spatial Working Memory | week 10 | 7.61 total number of correct trials | Standard Error 0.39 |
Secondary
Written Expression
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).
Time frame: baseline, study weeks 1, 8, 9, 10 &12
Population: some missing data due to attrition, non-valid responses, etc. # of participants with available data verified.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MPH Discontinuation | Written Expression | week 8 | 1.16 percentage of expected improvement | Standard Error 0.07 |
| MPH Discontinuation | Written Expression | week 10 | 1.04 percentage of expected improvement | Standard Error 0.07 |
| MPH Discontinuation | Written Expression | week 9 | 1.02 percentage of expected improvement | Standard Error 0.07 |
| MPH Discontinuation | Written Expression | week 12 | 0.91 percentage of expected improvement | Standard Error 0.06 |
| MPH Discontinuation | Written Expression | baseline | 1.00 percentage of expected improvement | Standard Error 0 |
| Sustained MPH | Written Expression | week 12 | 1.05 percentage of expected improvement | Standard Error 0.1 |
| Sustained MPH | Written Expression | baseline | 1.00 percentage of expected improvement | Standard Error 0 |
| Sustained MPH | Written Expression | week 8 | 0.94 percentage of expected improvement | Standard Error 0.08 |
| Sustained MPH | Written Expression | week 9 | 1.06 percentage of expected improvement | Standard Error 0.09 |
| Sustained MPH | Written Expression | week 10 | 0.93 percentage of expected improvement | Standard Error 0.08 |