The Effects of ADHD Medication (TEAM) Study
Study Details
Study Description
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 |
|---|---|---|
|
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: MPH Discontinuation 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. 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. 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 Names:
|
| Active Comparator: Sustained MPH 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. 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. 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 Names:
|
Outcome Measures
Primary Outcome Measures
- 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. Unit of measure is SD of the reaction time in msec. Minimum is 0, Maximum is 500. Higher scores indicate more variability 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
Secondary Outcome Measures
- Sluggish Cognitive Tempo (SCT) Ratings [baseline, study weeks 1, 2, 3, 4, 8, 9, 10 &12]
assessed via parent and teacher-completed Sluggish Cognitive Tempo Scale
- Executive Function Ratings [baseline, study weeks 1, 8, 9, 10 &12]
assessed via parent and teacher-completed Behavior Rating Inventory of Executive Function (BRIEF) scales
- Child Ratings of Depression [baseline, study weeks 1, 8, 9, 10 &12]
assessed via child-completed Children's Depression Inventory
- Child Ratings of Anxiety [baseline, study weeks 1, 8, 9, 10 &12]
assessed via child-completed Multidimensional Anxiety Scale for Children
- Child Ratings of Suicidality [baseline, study weeks 1, 8, 9, 10 &12]
assessed via child-completed Columbia Suicide Severity Rating Scale
- Parent Ratings of Emotional Regulation [baseline, study weeks 1, 8, 9, 10 &12]
assessed via parent-completed Emotion Regulation Checklist
- Side Effect Ratings [baseline, study weeks 1, 2, 3, 4, 8, 9, 10 &12]
assessed via parent- and teacher-completed Pittsburgh Side Effects Rating Scale
- Sleep Ratings [baseline, study weeks 1, 8, 9, 10 &12]
assessed via parent-completed Children's Sleep Habits Questionnaire
- Ecological Momentary Assessment [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
- Spatial Working Memory [baseline, study weeks 1, 8, 9, 10 &12]
Assessed via the Computerized Spatial Span Task
- Math Reasoning [baseline, study weeks 1, 8, 9, 10 &12]
Assessed by child's completion of the AIMSWEB CBM test of math concepts and applications
- Reading Fluency and Comprehension [baseline, study weeks 1, 8, 9, 10 &12]
Assessed by child's completion of the AIMSWEB CBM test of reading fluency and comprehension
- Written Expression [baseline, study weeks 1, 8, 9, 10 &12]
Assessed by child's completion of the AIMSWEB CBM test of written expression
- Spelling [baseline, study weeks 1, 8, 9, 10 &12]
Assessed by child's completion of the AIMSWEB CBM test of spelling.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
| 2 | Seattle Children's Hospital | Seattle | Washington | United States | 98105 |
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
Study Documents (Full-Text)
More Information
Publications
None provided.- ADHDMedTEAMStudy
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | MPH Discontinuation | Sustained MPH |
|---|---|---|
| Arm/Group Description | 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. 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. 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. | 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. 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. 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. |
| Period Title: Overall Study | ||
| STARTED | 92 | 17 |
| COMPLETED | 85 | 15 |
| NOT COMPLETED | 7 | 2 |
Baseline Characteristics
| Arm/Group Title | MPH Discontinuation | Sustained MPH | Total |
|---|---|---|---|
| Arm/Group Description | 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. 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. 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. | 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. 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. 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. | Total of all reporting groups |
| Overall Participants | 92 | 17 | 109 |
| Age (Count of Participants) | |||
| <=18 years |
92
100%
|
17
100%
|
109
100%
|
| Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
31
33.7%
|
6
35.3%
|
37
33.9%
|
| Male |
61
66.3%
|
11
64.7%
|
72
66.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
8
8.7%
|
1
5.9%
|
9
8.3%
|
| Not Hispanic or Latino |
84
91.3%
|
16
94.1%
|
100
91.7%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
2
2.2%
|
1
5.9%
|
3
2.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
7
7.6%
|
1
5.9%
|
8
7.3%
|
| White |
73
79.3%
|
15
88.2%
|
88
80.7%
|
| More than one race |
10
10.9%
|
0
0%
|
10
9.2%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
92
100%
|
17
100%
|
109
100%
|
| Parent Vanderbilt ADHD Total Symptom Score (score on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [score on a scale] |
36.2
(8.3)
|
34.6
(10.9)
|
36.0
(8.7)
|
Outcome Measures
| Title | Parent ADHD Total Symptom Scores |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| There was some attrition and missing data at different data collection points. |
| Arm/Group Title | MPH Discontinuation | Sustained MPH |
|---|---|---|
| Arm/Group Description | 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. 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. 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. | 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. 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. 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. |
| Measure Participants | 92 | 17 |
| Baseline |
36.2
(8.3)
|
34.6
(10.9)
|
| Maintenance Visit (week 8) |
17.6
(8.8)
|
15.3
(8.3)
|
| Randomization 1 (week 9) |
16.5
(12.0)
|
12.3
(10.4)
|
| Randomization 2 (week 10) |
23.8
(11.6)
|
14.3
(8.3)
|
| Randomization 3 (week 12) |
25.2
(11.6)
|
17.3
(12.3)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MPH Discontinuation, Sustained MPH |
|---|---|---|
| Comments | Compared at Baseline Time point | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.55 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.6 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.6 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | MPH Discontinuation, Sustained MPH |
|---|---|---|
| Comments | Comparison at MPH Maintenance Visit (Week 8) | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .30 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.41 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.3 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | MPH Discontinuation, Sustained MPH |
|---|---|---|
| Comments | Comparison at Randomization Phase 1 (Week 9) | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .28 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 4.01 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.9 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | MPH Discontinuation, Sustained MPH |
|---|---|---|
| Comments | Comparison at Randomization Phase 2 (Week 10) | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .00 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 9.64 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.5 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | MPH Discontinuation, Sustained MPH |
|---|---|---|
| Comments | Comparison at Randomization Phase 3 (Week 12) | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .01 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 7.96 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.2 |
|
| Estimation Comments | ||
| Title | Inhibitory Control Reaction Time Variability (SD of the Reaction Time) |
|---|---|
| Description | Assessed via the Go/No-Go computerized measure of inhibitory control reaction time variability. Unit of measure is SD of the reaction time in msec. Minimum is 0, Maximum is 500. Higher scores indicate more variability 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| There was some attrition and missing data at different data collection points. |
| Arm/Group Title | MPH Discontinuation | Sustained MPH |
|---|---|---|
| Arm/Group Description | 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. 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. 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. | 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. 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. 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. |
| Measure Participants | 89 | 14 |
| Baseline |
226.13
(139.2)
|
186.93
(91.8)
|
| Maintenance Visit (week 8) |
199.36
(113.1)
|
192.06
(119.6)
|
| Randomization 1 (week 9) |
275.11
(144.7)
|
177.95
(133.2)
|
| Randomization 2 (week 10) |
304.10
(157.0)
|
257.36
(196.5)
|
| Randomization 3 (week 12) |
319.46
(167.1)
|
189.91
(110.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MPH Discontinuation, Sustained MPH |
|---|---|---|
| Comments | Compared at baseline timepoint | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .16 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 36.04 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 25.4 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | MPH Discontinuation, Sustained MPH |
|---|---|---|
| Comments | Compared at Maintenance Time Point (week 8) | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .89 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 4.38 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 30.1 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | MPH Discontinuation, Sustained MPH |
|---|---|---|
| Comments | Compared at Randomization Phase 1 (week 9) | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .007 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 100.81 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 37.5 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | MPH Discontinuation, Sustained MPH |
|---|---|---|
| Comments | Compared at Randomization Phase 2 (week 10) | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .39 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 49.07 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 56.6 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | MPH Discontinuation, Sustained MPH |
|---|---|---|
| Comments | Compared at Randomization Phase 3 (week 12) | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .001 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 123.90 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 37.6 |
|
| Estimation Comments | ||
| Title | Math Computation - Number of Problems Completed Correctly |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| There was some attrition and missing data at different data collection points. |
| Arm/Group Title | MPH Discontinuation | Sustained MPH |
|---|---|---|
| Arm/Group Description | 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. 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. 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. | 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. 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. 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. |
| Measure Participants | 91 | 17 |
| Baseline |
200.84
(152.8)
|
230.93
(127.3)
|
| Maintenance Visit (week 8) |
264.71
(157.4)
|
320.12
(142.3)
|
| Randomization 1 (week 9) |
221.19
(175.3)
|
333.50
(214.1)
|
| Randomization 2 (week 10) |
201.69
(164.3)
|
323.25
(203.6)
|
| Randomization 3 (week 12) |
201.10
(180.3)
|
277.51
(190.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MPH Discontinuation, Sustained MPH |
|---|---|---|
| Comments | Comparison at Baseline | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .33 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 31.13 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 32.9 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | MPH Discontinuation, Sustained MPH |
|---|---|---|
| Comments | Comparison at Maintenance (week 8) | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .06 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 56.86 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 29.5 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | MPH Discontinuation, Sustained MPH |
|---|---|---|
| Comments | Comparison at Randomization Phase 1 (week 9) | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .02 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 108.78 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 46.8 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | MPH Discontinuation, Sustained MPH |
|---|---|---|
| Comments | Comparison at Randomization Phase 2 (week 10) | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .008 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 118.12 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 44.2 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | MPH Discontinuation, Sustained MPH |
|---|---|---|
| Comments | Comparison at Randomization Phase 3 (week 12) | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .07 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 77.09 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 42.9 |
|
| Estimation Comments | ||
| Title | Sluggish Cognitive Tempo (SCT) Ratings |
|---|---|
| Description | assessed via parent and teacher-completed Sluggish Cognitive Tempo Scale |
| Time Frame | baseline, study weeks 1, 2, 3, 4, 8, 9, 10 &12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Executive Function Ratings |
|---|---|
| Description | assessed via parent and teacher-completed Behavior Rating Inventory of Executive Function (BRIEF) scales |
| Time Frame | baseline, study weeks 1, 8, 9, 10 &12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Child Ratings of Depression |
|---|---|
| Description | assessed via child-completed Children's Depression Inventory |
| Time Frame | baseline, study weeks 1, 8, 9, 10 &12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Child Ratings of Anxiety |
|---|---|
| Description | assessed via child-completed Multidimensional Anxiety Scale for Children |
| Time Frame | baseline, study weeks 1, 8, 9, 10 &12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Child Ratings of Suicidality |
|---|---|
| Description | assessed via child-completed Columbia Suicide Severity Rating Scale |
| Time Frame | baseline, study weeks 1, 8, 9, 10 &12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Parent Ratings of Emotional Regulation |
|---|---|
| Description | assessed via parent-completed Emotion Regulation Checklist |
| Time Frame | baseline, study weeks 1, 8, 9, 10 &12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Side Effect Ratings |
|---|---|
| Description | assessed via parent- and teacher-completed Pittsburgh Side Effects Rating Scale |
| Time Frame | baseline, study weeks 1, 2, 3, 4, 8, 9, 10 &12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Sleep Ratings |
|---|---|
| Description | assessed via parent-completed Children's Sleep Habits Questionnaire |
| Time Frame | baseline, study weeks 1, 8, 9, 10 &12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Ecological Momentary Assessment |
|---|---|
| Description | 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 |
| Time Frame | Baseline, weeks 1, 8, and 9-12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Spatial Working Memory |
|---|---|
| Description | Assessed via the Computerized Spatial Span Task |
| Time Frame | baseline, study weeks 1, 8, 9, 10 &12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Math Reasoning |
|---|---|
| Description | Assessed by child's completion of the AIMSWEB CBM test of math concepts and applications |
| Time Frame | baseline, study weeks 1, 8, 9, 10 &12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Reading Fluency and Comprehension |
|---|---|
| Description | Assessed by child's completion of the AIMSWEB CBM test of reading fluency and comprehension |
| Time Frame | baseline, study weeks 1, 8, 9, 10 &12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Written Expression |
|---|---|
| Description | Assessed by child's completion of the AIMSWEB CBM test of written expression |
| Time Frame | baseline, study weeks 1, 8, 9, 10 &12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Spelling |
|---|---|
| Description | Assessed by child's completion of the AIMSWEB CBM test of spelling. |
| Time Frame | baseline, study weeks 1, 8, 9, 10 &12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | Duration of trial (3 months) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All-Cause Mortality: The occurrence of death due to any cause. Serious Adverse Events: adverse events resulting: death, life-threatening event, inpatient hospitalization, significant incapacity, inability to conduct normal functions, or a congenital anomaly. Important medical events may also be considered serious when they require medical or surgical intervention to prevent one of the outcomes listed in this definition. Other: Adverse events that are not Serious Adverse Events. | |||
| Arm/Group Title | MPH Discontinuation | Sustained MPH | ||
| Arm/Group Description | 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. 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. 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. | 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. 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. 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. | ||
All Cause Mortality |
||||
| MPH Discontinuation | Sustained MPH | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/92 (0%) | 0/18 (0%) | ||
Serious Adverse Events |
||||
| MPH Discontinuation | Sustained MPH | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/92 (1.1%) | 0/18 (0%) | ||
| Psychiatric disorders | ||||
| Suicidal Ideation | 1/92 (1.1%) | 1 | 0/18 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| MPH Discontinuation | Sustained MPH | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 55/92 (59.8%) | 15/18 (83.3%) | ||
| Gastrointestinal disorders | ||||
| Decreased appetite | 16/92 (17.4%) | 16 | 10/18 (55.6%) | 10 |
| Stomachache | 8/92 (8.7%) | 8 | 1/18 (5.6%) | 1 |
| General disorders | ||||
| Trouble Sleeping | 13/92 (14.1%) | 13 | 4/18 (22.2%) | 4 |
| Dull, tired, listless | 9/92 (9.8%) | 9 | 3/18 (16.7%) | 3 |
| Nervous system disorders | ||||
| Headache | 6/92 (6.5%) | 6 | 3/18 (16.7%) | 3 |
| Psychiatric disorders | ||||
| Irritability | 17/92 (18.5%) | 17 | 4/18 (22.2%) | 4 |
| Social Withdrawal | 2/92 (2.2%) | 2 | 1/18 (5.6%) | 1 |
| Sadness | 5/92 (5.4%) | 5 | 3/18 (16.7%) | 3 |
| Skin-picking | 13/92 (14.1%) | 13 | 1/18 (5.6%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 0/92 (0%) | 0 | 1/18 (5.6%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Tanya Froehlich, MD |
|---|---|
| Organization | Cincinnati Children's Hospital Medical Center |
| Phone | 5136361154 |
| tanya.froehlich@cchmc.org |
- ADHDMedTEAMStudy