Trial Outcomes & Findings for Study of the Effects of Osmotic-Release Oral System (OROS) Methylphenidate (Concerta) on Attention and Memory (NCT NCT00530257)

NCT ID: NCT00530257

Last Updated: 2011-12-19

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 30 participants
• Primary outcome timeframe: 2 weeks
• Results posted on: 2011-12-19

Participant Flow

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

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.

Participant milestones

Measure	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.
Overall Study STARTED	31
Overall Study COMPLETED	30
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure

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.

Overall Study Lost to Follow-up

1

Baseline Characteristics

Study of the Effects of Osmotic-Release Oral System (OROS) Methylphenidate (Concerta) on Attention and Memory

Baseline characteristics by cohort

Measure	OROS Methylphenidate n=30 Participants 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.
Age, Categorical <=18 years	30 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	8.5 years STANDARD_DEVIATION 1.9 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Medication n=30 Participants 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.	Placebo n=30 Participants This is a crossover study. Thirty of thirty-one enrolled subjects completed the medication and placebo phases
Test of Everyday Attention for Children: Walk, Don't Walk	13.5 units on a scale Interval 0.0 to 20.0	11 units on a scale Interval 0.0 to 19.0

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Medication n=29 Participants 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.	Placebo n=29 Participants This is a crossover study. Thirty of thirty-one enrolled subjects completed the medication and placebo phases
Gordon Diagnostic System Continuous Performance Test Omission Errors	2 errors Interval 0.0 to 31.0	4.5 errors Interval 0.0 to 42.0
Gordon Diagnostic System Continuous Performance Test Commission Errors	3 errors Interval 1.0 to 143.0	10.5 errors Interval 0.0 to 164.0

PRIMARY outcome

Timeframe: 2 weeks

Population: The 30 subjects who completed both arms of the crossover analysis

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.

Outcome measures

Measure	Medication n=30 Participants 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.	Placebo n=30 Participants This is a crossover study. Thirty of thirty-one enrolled subjects completed the medication and placebo phases
Wechsler Intelligence Scale for Children-IV, Digit Span Subtest	5.5 units on a scale Interval 0.0 to 10.0	5.0 units on a scale Interval 3.0 to 9.0

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Medication n=30 Participants 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.	Placebo n=30 Participants This is a crossover study. Thirty of thirty-one enrolled subjects completed the medication and placebo phases
Test of Everyday Attention for Children-Sky Search Dual Task	3.8 units on a scale Interval -3.3 to 429.0	3.9 units on a scale Interval -0.3 to 101.0

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Medication n=30 Participants 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.	Placebo n=30 Participants This is a crossover study. Thirty of thirty-one enrolled subjects completed the medication and placebo phases
Test of Everyday Attention for Children: Score Dual Task (DT)	14 units on a scale Interval 5.0 to 20.0	13 units on a scale Interval 3.0 to 19.0

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Medication n=30 Participants 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.	Placebo n=30 Participants This is a crossover study. Thirty of thirty-one enrolled subjects completed the medication and placebo phases
Test of Everyday Attention for Children: Creature Counting	4.9 units on a scale Interval 3.1 to 12.8	4.8 units on a scale Interval 3.1 to 28.2

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Medication n=30 Participants 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.	Placebo n=30 Participants This is a crossover study. Thirty of thirty-one enrolled subjects completed the medication and placebo phases
Test of Everyday Attention for Children: Map Mission	27.5 units on a scale Interval 15.0 to 57.0	27 units on a scale Interval 10.0 to 52.0

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Medication n=30 Participants 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.	Placebo n=30 Participants This is a crossover study. Thirty of thirty-one enrolled subjects completed the medication and placebo phases
Test of Everyday Attention for Children: Sky Search	5.8 units on a scale Interval 2.5 to 25.4	4.5 units on a scale Interval 2.3 to 26.0

PRIMARY outcome

Timeframe: 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

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..

Outcome measures

Measure	Medication n=30 Participants 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.	Placebo n=30 Participants This is a crossover study. Thirty of thirty-one enrolled subjects completed the medication and placebo phases
Test of Everyday Attention for Children: Opposite Worlds	38.5 units on a scale Interval 28.0 to 66.0	47.5 units on a scale Interval 27.0 to 63.0

SECONDARY outcome

Timeframe: 2 Weeks

Population: Although this was included in the protocol we have not analyzed the results of this rating scale

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Measure	Medication n=30 Participants 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.	Placebo n=30 Participants This is a crossover study. Thirty of thirty-one enrolled subjects completed the medication and placebo phases
ADHD Rating Scale-IV, Parent and Teacher Version Parent Inattention Rating	70.6 Percentile Standard Deviation 23.9	92.6 Percentile Standard Deviation 9.0
ADHD Rating Scale-IV, Parent and Teacher Version Parent Hyperactivity-Impulsivity Rating	64.8 Percentile Standard Deviation 26.5	89.6 Percentile Standard Deviation 13.1
ADHD Rating Scale-IV, Parent and Teacher Version Teacher Inattention Rating	61.1 Percentile Standard Deviation 23.2	73.3 Percentile Standard Deviation 19.9
ADHD Rating Scale-IV, Parent and Teacher Version Teacher Hyperactivity-Impulsivity Rating	58.1 Percentile Standard Deviation 22.1	75.2 Percentile Standard Deviation 19.8

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Medication n=28 Participants 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.	Placebo n=28 Participants This is a crossover study. Thirty of thirty-one enrolled subjects completed the medication and placebo phases
Stimulant Side Effect Rating Scale Euphoric	0.5 Units on a scale Standard Deviation 1.4	0.3 Units on a scale Standard Deviation 0.7
Stimulant Side Effect Rating Scale Insomnia	2.8 Units on a scale Standard Deviation 2.3	1.2 Units on a scale Standard Deviation 2.1
Stimulant Side Effect Rating Scale Nightmares	0.3 Units on a scale Standard Deviation 0.9	0.2 Units on a scale Standard Deviation 0.8
Stimulant Side Effect Rating Scale Stares/Day Dreams	1.1 Units on a scale Standard Deviation 1.7	0.8 Units on a scale Standard Deviation 1.3
Stimulant Side Effect Rating Scale Talks less with others	1 Units on a scale Standard Deviation 1.7	0.4 Units on a scale Standard Deviation 0.8
Stimulant Side Effect Rating Scale Uninterested in others	0.8 Units on a scale Standard Deviation 1.4	0.3 Units on a scale Standard Deviation 0.7
Stimulant Side Effect Rating Scale Decreased appetite	3.4 Units on a scale Standard Deviation 2.7	1 Units on a scale Standard Deviation 1.8
Stimulant Side Effect Rating Scale Irritable	2.6 Units on a scale Standard Deviation 2.4	1.7 Units on a scale Standard Deviation 1.9
Stimulant Side Effect Rating Scale Stomachaches	1.5 Units on a scale Standard Deviation 2.5	0.5 Units on a scale Standard Deviation 1.2
Stimulant Side Effect Rating Scale Headaches	0.9 Units on a scale Standard Deviation 1.8	0.3 Units on a scale Standard Deviation 0.9
Stimulant Side Effect Rating Scale Drowsiness	0.9 Units on a scale Standard Deviation 2.1	0.3 Units on a scale Standard Deviation 0.9
Stimulant Side Effect Rating Scale Sad	1.6 Units on a scale Standard Deviation 2	1 Units on a scale Standard Deviation 1.8
Stimulant Side Effect Rating Scale Prone to Crying	2.2 Units on a scale Standard Deviation 2.8	1.4 Units on a scale Standard Deviation 2.1
Stimulant Side Effect Rating Scale Anxiety	2.3 Units on a scale Standard Deviation 2.4	1.8 Units on a scale Standard Deviation 1.9
Stimulant Side Effect Rating Scale Bites fingernails	1.3 Units on a scale Standard Deviation 2.4	0.5 Units on a scale Standard Deviation 0.9
Stimulant Side Effect Rating Scale Dizziness	0.1 Units on a scale Standard Deviation 0.3	0.04 Units on a scale Standard Deviation 0.19

Adverse Events

OROS Methylphenidate

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	OROS Methylphenidate n=31 participants at risk 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 parents rated medication side effects on the Stimulant Side Effect Rating Scale (described previously). Score of 7-9 on this scale were considered adverse effects.	Placebo n=31 participants at risk 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 parents rated medication side effects on the Stimulant Side Effect Rating Scale (described previously). Score of 7-9 on this scale were considered adverse effects.
Gastrointestinal disorders decrease appetite	14.3% 4/28	3.6% 1/28
Nervous system disorders Irritable	10.7% 3/28	3.6% 1/28
Nervous system disorders stomachaches	7.1% 2/28	0.00% 0/28
Nervous system disorders Headaches	3.6% 1/28	0.00% 0/28
Nervous system disorders prone to crying	14.3% 4/28	3.6% 1/28
Psychiatric disorders Bites Fingernails	10.7% 3/28	0.00% 0/28
Nervous system disorders Tics/Nervous movements	3.6% 1/28	0.00% 0/28
Nervous system disorders Insomnia	7.1% 2/28	7.1% 2/28

Additional Information

Dr. Nathan Blum

The Children's Hospital of Philadelphia

Phone: 215-590-6336

Email: blum@email.chop.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place