Attention Deficit Hyperactivity Disorder
Conditions
Keywords
Attention Deficit Hyperactivity Disorder, Methylphenidate, Attention, Working Memory
Brief summary
This study investigates whether OROS-methylphenidate improves performance on different aspects of attention and memory in children with Attention-Deficit Hyperactivity Disorder (ADHD).
Detailed description
This study investigates the effect of Osmotic-Release Oral System (OROS)-methylphenidate, a long-acting stimulant, on multiple dimensions of attention and on working memory. Specifically, we will investigate the following two hypotheses: (1) OROS-methylphenidate will result in improved performance on measures assessing multiple domains of attention, including sustained attention, attentional control, selective attention, and divided attention, and (2) OROS-methylphenidate will result in improved performance on measures of working memory. In addition we will use the study to collect pilot data on whether the magnitude of the effect of OROS-methylphenidate varies across the different components of attention and working memory and whether improvement across any of these measures is helpful in predicting parent or teacher ratings of improvement.
Interventions
DRUGPlacebo
Placebo (sugar pill)
18 mg to 54 mg once a day for 1 week
Sponsors
Ortho-McNeil Janssen Scientific Affairs, LLC
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Meets Diagnostic and Statistical Manual-IV Edition (DSM-IV) Criteria for ADHD.Combined Type * Parent and Teacher Ratings \>85 percentile on inattention and/or hyperactivity/impulsivity scales * Estimated Intelligence Quotient (IQ) \> 80 on Wechsler Abbreviated Scale of Intelligence or similar IQ test
Exclusion criteria
* Past or current diagnosis of Tourette syndrome or chronic tic disorder, Pervasive Developmental Disorder (PDD), Cerebral Palsy, Head Injury requiring hospitalization, psychotic disorder, hypertension, glaucoma, cardiovascular disease, severe narrowing of the gastrointestinal tract, or epilepsy * Current diagnosis of bipolar disorder, obsessive-compulsive disorder serious enough to warrant separate treatment, suicidal or homicidal behavior or ideation * Use within 14-days of a monoamine oxidase inhibitor * History of side effects on any methylphenidate preparation that required stopping the medication * Inability to swallow a capsule or tablet * Chronic treatment with coumarin, clonidine, or tricyclic antidepressants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Test of Everyday Attention for Children: Opposite Worlds | 2 weeks | The TEA-Ch is a battery of subtests designed to assess multiple attentional capacities in children 6-16y.o. The Opposite Worlds subtest is a measure of attentional control and response inhibition. There is not a finite range of scores on this test. Lower scores indicate better performance.. |
| Test of Everyday Attention for Children: Creature Counting | 2 weeks | The TEA-Ch is a battery of nine subtests designed to assess multiple attentional capacities in children 6-16y.o. The Creature Counting subtest is a measure of attentional control. There is not a finite range for this test, but lower scores indicate better performance. |
| Test of Everyday Attention for Children: Map Mission | 2 weeks | The TEA-Ch is a battery of nine subtests designed to assess multiple attentional capacities in children 6-16y.o. The Map Mission subtest is a measure of selective attention and indicates the number of targets found in one minute. Scores on this subtest can range from 0 to over 70 with higher scores representing improved performance. |
| Test of Everyday Attention for Children: Sky Search | 2 weeks | The TEA-Ch is a battery of nine subtests designed to assess multiple attentional capacities in children 6-16y.o. The Sky Search subtest is a measure of selective attention. There is not a finite range of scores on this subtest, but lower scores indicate better performance. |
| Test of Everyday Attention for Children: Walk, Don't Walk | 2 weeks | The TEA-Ch is a battery of nine subtests designed to assess multiple attentional capacities in children 6-16y.o. The Walk-Don't Walk subtest is a measure of sustained attention and response inhibition. Scores on this subtest can range from 0 to 20 with higher scores representing better performance. |
| Gordon Diagnostic System Continuous Performance Test | 2 weeks | This is a measure of sustained attention & response inhibition for children 6 yrs and older. During this task a series of numbers flash, one at a time, on a screen. The subject is told to press a button every time a 1 is followed by a 9. There are 45 possible correct responses over the 9-minute task. Omission errors are a measure of sustained attention and can range from 0 to 45. Commission errors are a measure of sustained attention and response inhibition can range from zero to hundreds (each time the button is pushed at the incorrect time). Lower scores indicate better performance. |
| Wechsler Intelligence Scale for Children-IV, Digit Span Subtest | 2 weeks | The verbal assessment of working memory uses the digit span reversed component of the Digit Span subtest of the Wechsler Intelligence Scale for Children-IV edition (WISC-IV).Scores could range from 0 to 16 with higher scores indicating better performance. |
| Test of Everyday Attention for Children-Sky Search Dual Task | 2 weeks | The TEA-Ch is a battery of nine subtests designed to assess multiple attentional capacities in children 6-16y.o. The Sky Search Dual Task is a measure of sustained attention. Lower scores indicate better performance. There is not a finite range for this test and very high scores can be negative numbers. |
| Test of Everyday Attention for Children: Score Dual Task (DT) | 2 weeks | The TEA-Ch is a battery of nine subtests designed to assess multiple attentional capacities in children 6-16y.o. The Score DT subtest is a measure of sustained attention. and response inhibition. Scores on this subtest can range from 0 to 20 with higher scores representing better performance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Behavior Rating Inventory of Executive Function | 2 Weeks | — |
| ADHD Rating Scale-IV, Parent and Teacher Version | 2 Weeks | This is the parent and teacher version of the ADHD Rating Scale-IV. The scale has 2 subscales, one for inattention and one for hyperactivity-impulsivity. The scores provided are percentile scores and can range from 1 to 99 percent. Higher scores indicate more problems in inattention or with hyperactivity-impulsivity |
Other
| Measure | Time frame | Description |
|---|---|---|
| Stimulant Side Effect Rating Scale | 2 weeks | Parents rate 16 possible stimulant side effects on a 10 point likert scale from 0-9 with 0 indicating no side effects and 9 indicating more severe symptoms. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from an outpatient ADHD evaluation and treatment program at a pediatric academic medical center. Eligible children wer: 1) Age 6-12 years and at least in 1st grade; 2) DSM-IVTR diagnosis of ADHD, Combined Type;3) Parent and teacher ratings on the ADHD Rating Scale-IV \> 85th percentile; 5) IQ greater than 75
Pre-assignment details
Parents of 41 patients inquired about participating in the study. Four did not meet eligibility requirements leaving 37 eligible children. Three families elected not to participate leaving 34 children. Three children did not complete the dose finding stage leaving 31 children who entered the double blind placebo controlled crossover study.
Participants by arm
| Arm | Count |
|---|---|
| OROS Methylphenidate Children participated in a double blind placebo controlled crossover study comparing one week of treatment with the optimal dose of OROS methylphenidate with one week of treatment with placebo. The order of administering OROS-methylphenidate versus placebo was randomized and counterbalanced across participants. At the end of each week the child's performance on different domains of attention and executive functioning was assessed on the measures described below. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | OROS Methylphenidate |
|---|---|
| Age, Categorical <=18 years | 30 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age Continuous | 8.5 years STANDARD_DEVIATION 1.9 |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 31 | 5 / 31 |
| serious Total, serious adverse events | 0 / 31 | 0 / 31 |
Outcome results
Primary
Gordon Diagnostic System Continuous Performance Test
This is a measure of sustained attention & response inhibition for children 6 yrs and older. During this task a series of numbers flash, one at a time, on a screen. The subject is told to press a button every time a 1 is followed by a 9. There are 45 possible correct responses over the 9-minute task. Omission errors are a measure of sustained attention and can range from 0 to 45. Commission errors are a measure of sustained attention and response inhibition can range from zero to hundreds (each time the button is pushed at the incorrect time). Lower scores indicate better performance.
Time frame: 2 weeks
Population: 31 participants began the crossover phase of the trial and 30 completed both the medication and placebo arms. For one patient there was an equipment problem so that subject did not have data available
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Medication | Gordon Diagnostic System Continuous Performance Test | Omission Errors | 2 errors |
| Medication | Gordon Diagnostic System Continuous Performance Test | Commission Errors | 3 errors |
| Placebo | Gordon Diagnostic System Continuous Performance Test | Omission Errors | 4.5 errors |
| Placebo | Gordon Diagnostic System Continuous Performance Test | Commission Errors | 10.5 errors |
Comparison: Same as described for TEA-Ch Walk, Don't Walkp-value: <0.01Wilcoxon (Mann-Whitney)
Primary
Test of Everyday Attention for Children: Creature Counting
The TEA-Ch is a battery of nine subtests designed to assess multiple attentional capacities in children 6-16y.o. The Creature Counting subtest is a measure of attentional control. There is not a finite range for this test, but lower scores indicate better performance.
Time frame: 2 weeks
Population: Crossover design, all 30 of the 31 subjects completed both the placebo and medication phase of the study and were the group analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Medication | Test of Everyday Attention for Children: Creature Counting | 4.9 units on a scale |
| Placebo | Test of Everyday Attention for Children: Creature Counting | 4.8 units on a scale |
Comparison: Same as described for TEA-Ch: Walk, Don't Walkp-value: <0.01Wilcoxon (Mann-Whitney)
Primary
Test of Everyday Attention for Children: Map Mission
The TEA-Ch is a battery of nine subtests designed to assess multiple attentional capacities in children 6-16y.o. The Map Mission subtest is a measure of selective attention and indicates the number of targets found in one minute. Scores on this subtest can range from 0 to over 70 with higher scores representing improved performance.
Time frame: 2 weeks
Population: Crossover design, all 30 of the 31 subjects completed both the placebo and medication phase of the study and were the group analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Medication | Test of Everyday Attention for Children: Map Mission | 27.5 units on a scale |
| Placebo | Test of Everyday Attention for Children: Map Mission | 27 units on a scale |
Comparison: Same as described for TEA-Ch: Walk, Don't Walkp-value: <0.01Wilcoxon (Mann-Whitney)
Primary
Test of Everyday Attention for Children: Opposite Worlds
The TEA-Ch is a battery of subtests designed to assess multiple attentional capacities in children 6-16y.o. The Opposite Worlds subtest is a measure of attentional control and response inhibition. There is not a finite range of scores on this test. Lower scores indicate better performance..
Time frame: 2 weeks
Population: Crossover design, all 30 of the 31 subjects completed both the placebo and medication phase of the study and were the group analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Medication | Test of Everyday Attention for Children: Opposite Worlds | 38.5 units on a scale |
| Placebo | Test of Everyday Attention for Children: Opposite Worlds | 47.5 units on a scale |
Comparison: Same as described for TEA-Ch: Walk, Don't Walkp-value: <0.01Wilcoxon (Mann-Whitney)
Primary
Test of Everyday Attention for Children: Score Dual Task (DT)
The TEA-Ch is a battery of nine subtests designed to assess multiple attentional capacities in children 6-16y.o. The Score DT subtest is a measure of sustained attention. and response inhibition. Scores on this subtest can range from 0 to 20 with higher scores representing better performance.
Time frame: 2 weeks
Population: Crossover design, all 30 of the 31 subjects completed both the placebo and medication phase of the study and were the group analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Medication | Test of Everyday Attention for Children: Score Dual Task (DT) | 14 units on a scale |
| Placebo | Test of Everyday Attention for Children: Score Dual Task (DT) | 13 units on a scale |
p-value: <0.01Wilcoxon (Mann-Whitney)
Primary
Test of Everyday Attention for Children: Sky Search
The TEA-Ch is a battery of nine subtests designed to assess multiple attentional capacities in children 6-16y.o. The Sky Search subtest is a measure of selective attention. There is not a finite range of scores on this subtest, but lower scores indicate better performance.
Time frame: 2 weeks
Population: Crossover design, all 30 of the 31 subjects completed both the placebo and medication phase of the study and were the group analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Medication | Test of Everyday Attention for Children: Sky Search | 5.8 units on a scale |
| Placebo | Test of Everyday Attention for Children: Sky Search | 4.5 units on a scale |
Comparison: Same as described for TEA-Ch: Walk, Don't Walkp-value: <0.01Wilcoxon (Mann-Whitney)
Primary
Test of Everyday Attention for Children-Sky Search Dual Task
The TEA-Ch is a battery of nine subtests designed to assess multiple attentional capacities in children 6-16y.o. The Sky Search Dual Task is a measure of sustained attention. Lower scores indicate better performance. There is not a finite range for this test and very high scores can be negative numbers.
Time frame: 2 weeks
Population: Crossover design, all 30 of the 31 subjects completed both the placebo and medication phase of the study and were the group analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Medication | Test of Everyday Attention for Children-Sky Search Dual Task | 3.8 units on a scale |
| Placebo | Test of Everyday Attention for Children-Sky Search Dual Task | 3.9 units on a scale |
Comparison: Same as described for TEA-Ch: Walk, Don't Walkp-value: <0.01Wilcoxon (Mann-Whitney)
Primary
Test of Everyday Attention for Children: Walk, Don't Walk
The TEA-Ch is a battery of nine subtests designed to assess multiple attentional capacities in children 6-16y.o. The Walk-Don't Walk subtest is a measure of sustained attention and response inhibition. Scores on this subtest can range from 0 to 20 with higher scores representing better performance.
Time frame: 2 weeks
Population: Crossover design, all 30 of the 31 subjects completed both the placebo and medication phase of the study and were the group analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Medication | Test of Everyday Attention for Children: Walk, Don't Walk | 13.5 units on a scale |
| Placebo | Test of Everyday Attention for Children: Walk, Don't Walk | 11 units on a scale |
Comparison: We evaluated the data for cross over effects. No statistical significant sequence effect were seen for our endpoints and hence we combined the data from both periods of the crossover design There was evidence against the assumption of normality for performance on some of the measures of attention. Thus we used the non-parametric Wilcoxon Signed Ranks Test to compare performance on OROS-methylphenidate versus placebo.p-value: <0.01Wilcoxon (Mann-Whitney)
Primary
Wechsler Intelligence Scale for Children-IV, Digit Span Subtest
The verbal assessment of working memory uses the digit span reversed component of the Digit Span subtest of the Wechsler Intelligence Scale for Children-IV edition (WISC-IV).Scores could range from 0 to 16 with higher scores indicating better performance.
Time frame: 2 weeks
Population: The 30 subjects who completed both arms of the crossover analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Medication | Wechsler Intelligence Scale for Children-IV, Digit Span Subtest | 5.5 units on a scale |
| Placebo | Wechsler Intelligence Scale for Children-IV, Digit Span Subtest | 5.0 units on a scale |
Comparison: We evaluated the data for cross over effects. No statistical significant sequence effect were seen for our endpoints and hence we combined the data from both periods of the crossover design There was evidence against the assumption of normality for performance on some of the measures of attention. Thus we used the non-parametric Wilcoxon Signed Ranks Test to compare performance on OROS-methylphenidate versus placebo.p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
ADHD Rating Scale-IV, Parent and Teacher Version
This is the parent and teacher version of the ADHD Rating Scale-IV. The scale has 2 subscales, one for inattention and one for hyperactivity-impulsivity. The scores provided are percentile scores and can range from 1 to 99 percent. Higher scores indicate more problems in inattention or with hyperactivity-impulsivity
Time frame: 2 Weeks
Population: We had complete data for all 30 subjects for the parent rating scale. We only had 24 sets of complete data for the teacher rating scale as some teachers did not return a rating scale when the subject was on both medication and placebo
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Medication | ADHD Rating Scale-IV, Parent and Teacher Version | Teacher Inattention Rating | 61.1 Percentile | Standard Deviation 23.2 |
| Medication | ADHD Rating Scale-IV, Parent and Teacher Version | Parent Inattention Rating | 70.6 Percentile | Standard Deviation 23.9 |
| Medication | ADHD Rating Scale-IV, Parent and Teacher Version | Teacher Hyperactivity-Impulsivity Rating | 58.1 Percentile | Standard Deviation 22.1 |
| Medication | ADHD Rating Scale-IV, Parent and Teacher Version | Parent Hyperactivity-Impulsivity Rating | 64.8 Percentile | Standard Deviation 26.5 |
| Placebo | ADHD Rating Scale-IV, Parent and Teacher Version | Teacher Hyperactivity-Impulsivity Rating | 75.2 Percentile | Standard Deviation 19.8 |
| Placebo | ADHD Rating Scale-IV, Parent and Teacher Version | Parent Inattention Rating | 92.6 Percentile | Standard Deviation 9 |
| Placebo | ADHD Rating Scale-IV, Parent and Teacher Version | Teacher Inattention Rating | 73.3 Percentile | Standard Deviation 19.9 |
| Placebo | ADHD Rating Scale-IV, Parent and Teacher Version | Parent Hyperactivity-Impulsivity Rating | 89.6 Percentile | Standard Deviation 13.1 |
Comparison: A paired t-test was used to compare the medication versus placebo.p-value: <0.05t-test, 2 sided
Secondary
Behavior Rating Inventory of Executive Function
Time frame: 2 Weeks
Population: Although this was included in the protocol we have not analyzed the results of this rating scale
Other Pre-specified
Stimulant Side Effect Rating Scale
Parents rate 16 possible stimulant side effects on a 10 point likert scale from 0-9 with 0 indicating no side effects and 9 indicating more severe symptoms.
Time frame: 2 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Medication | Stimulant Side Effect Rating Scale | Insomnia | 2.8 Units on a scale | Standard Deviation 2.3 |
| Medication | Stimulant Side Effect Rating Scale | Nightmares | 0.3 Units on a scale | Standard Deviation 0.9 |
| Medication | Stimulant Side Effect Rating Scale | Stares/Day Dreams | 1.1 Units on a scale | Standard Deviation 1.7 |
| Medication | Stimulant Side Effect Rating Scale | Talks less with others | 1 Units on a scale | Standard Deviation 1.7 |
| Medication | Stimulant Side Effect Rating Scale | Uninterested in others | 0.8 Units on a scale | Standard Deviation 1.4 |
| Medication | Stimulant Side Effect Rating Scale | Decreased appetite | 3.4 Units on a scale | Standard Deviation 2.7 |
| Medication | Stimulant Side Effect Rating Scale | Irritable | 2.6 Units on a scale | Standard Deviation 2.4 |
| Medication | Stimulant Side Effect Rating Scale | Stomachaches | 1.5 Units on a scale | Standard Deviation 2.5 |
| Medication | Stimulant Side Effect Rating Scale | Headaches | 0.9 Units on a scale | Standard Deviation 1.8 |
| Medication | Stimulant Side Effect Rating Scale | Drowsiness | 0.9 Units on a scale | Standard Deviation 2.1 |
| Medication | Stimulant Side Effect Rating Scale | Sad | 1.6 Units on a scale | Standard Deviation 2 |
| Medication | Stimulant Side Effect Rating Scale | Prone to Crying | 2.2 Units on a scale | Standard Deviation 2.8 |
| Medication | Stimulant Side Effect Rating Scale | Anxiety | 2.3 Units on a scale | Standard Deviation 2.4 |
| Medication | Stimulant Side Effect Rating Scale | Bites fingernails | 1.3 Units on a scale | Standard Deviation 2.4 |
| Medication | Stimulant Side Effect Rating Scale | Euphoric | 0.5 Units on a scale | Standard Deviation 1.4 |
| Medication | Stimulant Side Effect Rating Scale | Dizziness | 0.1 Units on a scale | Standard Deviation 0.3 |
| Placebo | Stimulant Side Effect Rating Scale | Dizziness | 0.04 Units on a scale | Standard Deviation 0.19 |
| Placebo | Stimulant Side Effect Rating Scale | Insomnia | 1.2 Units on a scale | Standard Deviation 2.1 |
| Placebo | Stimulant Side Effect Rating Scale | Headaches | 0.3 Units on a scale | Standard Deviation 0.9 |
| Placebo | Stimulant Side Effect Rating Scale | Nightmares | 0.2 Units on a scale | Standard Deviation 0.8 |
| Placebo | Stimulant Side Effect Rating Scale | Anxiety | 1.8 Units on a scale | Standard Deviation 1.9 |
| Placebo | Stimulant Side Effect Rating Scale | Stares/Day Dreams | 0.8 Units on a scale | Standard Deviation 1.3 |
| Placebo | Stimulant Side Effect Rating Scale | Drowsiness | 0.3 Units on a scale | Standard Deviation 0.9 |
| Placebo | Stimulant Side Effect Rating Scale | Talks less with others | 0.4 Units on a scale | Standard Deviation 0.8 |
| Placebo | Stimulant Side Effect Rating Scale | Euphoric | 0.3 Units on a scale | Standard Deviation 0.7 |
| Placebo | Stimulant Side Effect Rating Scale | Uninterested in others | 0.3 Units on a scale | Standard Deviation 0.7 |
| Placebo | Stimulant Side Effect Rating Scale | Sad | 1 Units on a scale | Standard Deviation 1.8 |
| Placebo | Stimulant Side Effect Rating Scale | Decreased appetite | 1 Units on a scale | Standard Deviation 1.8 |
| Placebo | Stimulant Side Effect Rating Scale | Bites fingernails | 0.5 Units on a scale | Standard Deviation 0.9 |
| Placebo | Stimulant Side Effect Rating Scale | Irritable | 1.7 Units on a scale | Standard Deviation 1.9 |
| Placebo | Stimulant Side Effect Rating Scale | Prone to Crying | 1.4 Units on a scale | Standard Deviation 2.1 |
| Placebo | Stimulant Side Effect Rating Scale | Stomachaches | 0.5 Units on a scale | Standard Deviation 1.2 |