Lab School Day Study for CONCERTA of Older Children With ADHD

Study Overview
=================
Brief Summary
-----------------
The purpose of this trial is to determine if the study medication, CONCERTA (methylphenidate HCl), is safe and effective in improving academic performance and behavior in children with attention deficit hyperactivity disorder (ADHD), when compared to placebo.

Detailed Description
-----------------
The hypothesis is that CONCERTA (methylphenidate HCl) is safe and effective in improving academic performance and behavior in children with ADHD, when compared to placebo as demonstrated using specified study measures. This is a double-blind (neither participant nor investigator knows the name of the assigned study drug), randomized (study drug assigned by chance), placebo-controlled, crossover study evaluating the academic, behavioral, and cognitive effects of CONCERTA (methylphenidate HCl) on older children with ADHD. This means that all eligible children will receive treatment with methylphenidate HCl throughout the study (the titration and assessment periods) and inactive pill (placebo) on one of the two laboratory classroom days. On the other laboratory classroom day they will receive their regular dose of methylphenidate HCl. The primary efficacy variable in this study is the Permanent Product Math Test (PERMP) attempted score. Secondary Measures include: SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham), tests of inattention, reading fluency and comprehension, and memory. Assessments will be completed during each of the laboratory assessment days (12.5 hours). Participants will be assessed for adverse events throughout the study. Patients will initiate treatment with oral CONCERTA (methylphenidate HCl) 18 mg at baseline and continue morning dosing with increases every 3 to 7 days until an optimal dose is achieved, up to the maximum of 54 mg/day. Eligible patients will remain in the study for a maximum of 8 weeks.

Official Title
-----------------
The ABC Study: A Double-Blind, Randomized, Placebo-Controlled, Crossover Study Evaluating the Academic, Behavioral, and Cognitive Effects of CONCERTA on Older Children With ADHD

Conditions
-----------------
Attention Deficit Hyperactivity Disorder

Intervention / Treatment
-----------------
* Drug: Placebo/ CONCERTA (methylphenidate HCl)
* Drug: CONCERTA (methylphenidate HCl) / Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ADHD diagnosis of all subtypes (except Not Otherwise Specified) Patients with total or subscale Attention Deficit Hyperactivity Disorder Rating Scale (ADHD RS-IV) scores > =90th percentile relative to the general population of children by age and gender Patients currently receiving ADHD medication must be inadequately managed on their current stimulant dose and meet this criteria at the screening visit Ability to read and understand English Ability to attend school regularly. Exclusion Criteria: Estimated Full Scale IQ score of 80 or below Severe Learning Disability History of, or current, primary diagnosis of: severe anxiety disorder, conduct disorder, psychotic disorders, pervasive developmental disorder, eating disorder, obsessive-compulsive disorder, sleep disorder, major depressive disorder, bipolar disorder, substance use disorder, chronic tic disorder, personal or family history of Tourette's syndrome Weight < 3rd percentile for age History of hospitalization for treatment of a mood, anxiety, or psychotic disorder History of failed response to methylphenidate.

Ages Eligible for Study
-----------------
Minimum Age: 9 Years
Maximum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>CONCERTA (methylphenidate HCl) / Placebo Optimal Subject Dose (18 mg-54 mg) once daily during Lab School Day #1 and Placebo once daily on Lab School Day #2 | Drug: CONCERTA (methylphenidate HCl) / Placebo<br>* Optimal Subject Dose (18 mg-54 mg) once daily during Lab School Day #1 and Placebo once daily on Lab School Day #2<br>|
| Experimental: 2<br>Placebo/ CONCERTA (methylphenidate HCl) Placebo once daily on Lab School Day #1 and Optimal Subject Dose (18 mg-54 mg) once daily during Lab School Day #2 | Drug: Placebo/ CONCERTA (methylphenidate HCl)<br>* Placebo once daily on Lab School Day #1 and Optimal Subject Dose (18 mg-54 mg) once daily during Lab School Day #2<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hour 4 Permanent Product Math Test Attempted Score (PERMP-Attempted) | PERMP (range: 0, 400) is a measure of academic productivity in children up to 14 years of age. These seatwork math tasks provide an objective measure of attention and accuracy in calculations. The level of difficulty is established on a screening math pretest. The subsequent laboratory school day assessments employed a series of 10-minute math tests (5 pages of 80 math problem each for a total of 400 problems available). Children were graded on the number of attempted problems. A higher number of problems attempted was indicative of greater attention to detail (higher score is preferable) | Hour 4 of the of the Lab School Day during Double-Blind Assessment Period | 
| Hour 4 Permanent Product Math Test Correct Score (PERMP-Correct) | PERMP (range: 0, 400) is a measure of academic productivity in children up to 14 years of age. These seatwork math tasks provide an objective measure of attention and accuracy in calculations. The level of difficulty is established on a screening math pretest performed at Visit 2. The subsequent laboratory school day assessments employed a series of 10-minute math tests (5 pages of 80 math problem each for a total of 400 problems available). Children were graded on the number of correct problems. A higher number of problems correct, of those attempted, was indicative of greater accuracy. | Hour 4 of the Lab School Day During the Double-Blind Assessment Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Deportment (SKAMP-Deportment) | The SKAMP scale measures the manifestations of ADHD using an independent observer (teacher) rating of the child's impairment in classroom behavior. The SKAMP-Deportment (SKAMP-D) (range: 0, 36) is a sum of ratings on 6 deportment items (interacting with other children, interacting with adults, remaining quiet, staying seated, complying with the teacher's directions, and following the classroom rules). Each item was rated on a 7-point impairment scale (0=normal, 6=maximum impairment), with higher scores indicating more severe symptoms. | Hour 4 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Attention (SKAMP-Attention) | The SKAMP scale measures the manifestations of ADHD using an independent observer (teacher) rating of the child's impairment in classroom behavior. The SKAMP-Attention (SKAMP-A) (range: 0, 42) is a sum of the ratings on 7 attention items (getting started, sticking with tasks, attending to an activity, making activity transitions, completing assigned tasks, performing work accurately, and being neat and careful while writing or drawing). Each item was rated on a 7-point impairment scale (0=normal, 6=maximum impairment), with higher scores indicating more severe symptoms. | Hour 4 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Composite (SKAMP-Composite) | The SKAMP scale measures the manifestations of ADHD using an independent observer (teacher) rating of the child's impairment in classroom behavior. A composite score (range: 0, 78) for the SKAMP variable (13 items total) was obtained by summing the SKAMP-D and SKAMP-A subscale scores. A lower score was preferable, as a higher score represented greater behavioral impairment. | Hour 4 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 5.5 Test of Variables of Attention (TOVA) ADHD Composite Cutoff Score | The TOVA (range: unbounded) is a computerized, visual continuous performance test providing a measure of attention. The stimulus, presented for 100 milliseconds (ms) at the rate of 30 per minute, is a computer-presented square containing a square hole near the top (target) or bottom (non-target) edge. Higher scores indicate better performance, lower scores indicate worse performance. Clinical interpretation: an ADHD scores of -1.80 or lower (<= -1.80) are considered not within normal limits scores above -1.80 (> -1.80) are considered inconclusive (meaning, neither like-ADHD nor like-normal). | Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 5.5 Test of Variables of Attention (TOVA) Reaction Time Standard Score | The TOVA (range: unbounded) is a computerized, visual continuous performance test providing a measure of attention. The stimulus, presented for 100 milliseconds (ms) at the rate of 30 per minute, is a computer-presented square containing a square hole near the top (target) or bottom (non-target) edge. Higher scores indicated better performance, lower scores indicate worse performance. Clinical interpretation: scores below 80 are considered abnormal, 80-85 are considered borderline, and scores above 85 are considered within normal limits. | Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 5.5 Test of Variables of Attention (TOVA) Reaction Time Variability Standard Score | The TOVA (range: unbounded) is a computerized, visual continuous performance test providing a measure of attention. The stimulus, presented for 100 milliseconds (ms) at the rate of 30 per minute, is a computer-presented square containing a square hole near the top (target) or bottom (non-target) edge. Higher scores indicated better performance, lower scores indicate worse performance. Clinical interpretation: scores below 80 are considered abnormal, 80-85 are considered borderline, and scores above 85 are considered within normal limits. | Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 5.5 Wide Range Assessment of Memory and Learning (WRAML-2) Finger Windows Backwards | WRAML-2 (range: 0, 28) is designed to evaluate a child's ability to learn and to memorize information, consists of 9 subtests from which 4 summary indexes can be calculated: verbal memory index, visual memory index, learning index, and general memory index. During this test the investigator pointed to a longer and longer series of windows on a card at the rate of 1 location per second, and then the child was asked to reproduce the sequence exactly in reverse order. One point was given for each correctly recalled sequence, and the test was discontinued after 3 consecutive errors. | Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 5.5 Wide Range Assessment of Memory and Learning (WRAML-2) Finger Windows Forwards | WRAML-2 (range: 0, 28) is designed to evaluate a child's ability to learn and to memorize information, consists of 9 subtests from which 4 summary indexes can be calculated: verbal memory index, visual memory index, learning index, and general memory index. During this test the investigator pointed to a longer and longer series of windows on a card at the rate of 1 location per second, and then the child was asked to reproduce the sequence exactly. One point was given for each correctly recalled sequence, and the test was discontinued after 3 consecutive errors. | Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 5.5 Test of Variables of Attention (TOVA) Commissions Standard Score | The TOVA (range: unbounded) is a computerized, visual continuous performance test providing a measure of attention. The stimulus, presented for 100 milliseconds (ms) at the rate of 30 per minute, is a computer-presented square containing a square hole near the top (target) or bottom (non-target) edge. Higher scores indicated better performance, lower scores indicate worse performance. Clinical interpretation: scores below 80 are considered abnormal, 80-85 are considered borderline, and scores above 85 are considered within normal limits. | Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 5.5 Wechsler Intelligence Scale for Children - 3rd ed. (WISC-III-PI) Digit Span Backwards | Each child individually was given a sequence of numbers with the sequence becoming progressively longer. The child was then asked to repeat the digits in the same sequence, either forwards or backwards. Each sequence length was attempted twice. The test was complete after failure on both trials of any sequence length. One point was awarded if the participant passed only 1 trial of a sequence length. Zero points were given if the participant failed both trials. The maximum raw scores were 16 forwards and 14 backwards. A higher score was indicative of better recall and attention (range: 0, 14). | Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 8.75 Gray Silent Reading Test (GSRT) Reading Quotient | Gray Silent Reading Test (GSRT)Reading Quotient is a reliable, validated measure of reading comprehension administered in the group setting during the first half hour of the homework session (range: 0,unbounded). A higher score is preferable as it means more questions were answered correctly. | Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 7.5 Test of Handwriting Skills (Revised) (THS-R) Standard Score | The THS-R (range: unbounded) is a standardized, untimed assessment designed to evaluate neurosensory integration manifested in manuscript and cursive writing. The test includes subtests: writing from memory or dictation the letters of the alphabet in order, single digit-numbers out of order, selected words, and copying selected letters, words, and sentences. Each subtest was scored from zero (poorly formed letters) to 3 (perfectly formed letters). 100 is the normal mean; scores lower than 100 indicate performance worse than normal, scores above 100 indicate performance better than normal. | Hour 7.5 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 3.5 Dynamic Indicators of Basic Early Literacy Skills (DIBELS) | The DIBELS (range: 0, 376), used to assess reading fluency, consists of standardized, individually administered measures of early literacy development. These short (1 minute) fluency measures were developed based upon essential early literacy domains to assess development of phonological awareness, alphabetic understanding, and automaticity and fluency. Only the paragraph fluency component of an age/grade-appropriate DIBELS was used. A higher score indicated better performance, as it represented that the subject orally read a greater number of words correctly within the time allowed. | Hour 3.5 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 5.5 Wechsler Intelligence Scale for Children - 3rd ed. (WISC-III-PI) Digit Span Forwards | Each child individually was given a sequence of numbers with the sequence becoming progressively longer. The child was then asked to repeat the digits in the same sequence, either forwards or backwards. Each sequence length was attempted twice. The test was complete after failure on both trials of any sequence length. One point was awarded if the participant passed only 1 trial of a sequence length. Zero points were given if the participant failed both trials. The maximum raw scores were 16 forwards and 14 backwards. A higher score was indicative of better recall and attention (range: 0, 16). | Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 5.5 Test of Variables of Attention (TOVA) Omissions Standard Score | The TOVA (range: unbounded) is a computerized, visual continuous performance test providing a measure of attention. The stimulus, presented for 100 milliseconds (ms) at the rate of 30 per minute, is a computer-presented square containing a square hole near the top (target) or bottom (non-target) edge. Higher scores indicated better performance, lower scores indicate worse performance. Clinical interpretation: scores below 80 are considered abnormal, 80-85 are considered borderline, and scores above 85 are considered within normal limits. | Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 3.0 Grammar Task | This task, presented once during a laboratory school day, was designed to index attention to detail by determining how many grammatical mistakes each child could identify and circle in a brief paragraph. The errors were not difficult to identify and were designed to show attention to task, not comprehension. A higher number of errors identified, of those possible, was indicative of better attention - identification of grammatical errors(range: 0, 1 represents correct responses divided by the number of possible responses). | Hour 3.0 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 8.75 Packet Activity Short Story With Questions for Comprehension | Packet Activities: Assessment of ability to organize, listen to instructions, initiate task, complete task, and distractibility, by completing a word search, reading a short story for comprehension on a multiple choice test, reading a longer story for comprehension on a true/false test, decoding a mystery sentence, and completing various vocabulary assessments (word choice, homophones; base/root words, alphabetic order) (range: 0, 1 represents correct responses divided by the number of possible responses). | Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 8.75 Packet Activity Identify Root Word | Packet Activities: Assessment of ability to organize, listen to instructions, initiate task, complete task, and distractibility, by completing a word search, reading a short story for comprehension on a multiple choice test, reading a longer story for comprehension on a true/false test, decoding a mystery sentence, and completing various vocabulary assessments (word choice, homophones; base/root words, alphabetic order) (range: 0, 1 represents correct responses divided by the number of possible responses). | Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 8.75 Packet Activity Alphabetize List of Words | Packet Activities: Assessment of ability to organize, listen to instructions, initiate task, complete task, and distractibility, by completing a word search, reading a short story for comprehension on a multiple choice test, reading a longer story for comprehension on a true/false test, decoding a mystery sentence, and completing various vocabulary assessments (word choice, homophones; base/root words, alphabetic order) (range: 0, 1 represents correct responses divided by the number of possible responses). | Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 8.75 Packet Activity Identify Multiple Meanings for Words | Packet Activities: Assessment of ability to organize, listen to instructions, initiate task, complete task, and distractibility, by completing a word search, reading a short story for comprehension on a multiple choice test, reading a longer story for comprehension on a true/false test, decoding a mystery sentence, and completing various vocabulary assessments (word choice, homophones; base/root words, alphabetic order) (range: 0, 1 represents correct responses divided by the number of possible responses). | Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 8.75 Packet Activity Complete Sentences Using Words Provided | Packet Activities: Assessment of ability to organize, listen to instructions, initiate task, complete task, and distractibility, by completing a word search, reading a short story for comprehension on a multiple choice test, reading a longer story for comprehension on a true/false test, decoding a mystery sentence, and completing various vocabulary assessments (word choice, homophones; base/root words, alphabetic order) (range: 0, 1 represents correct responses divided by the number of possible responses). | Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 8.75 Packet Activity Word Search | Packet Activities: Assessment of ability to organize, listen to instructions, initiate task, complete task, and distractibility, by completing a word search, reading a short story for comprehension on a multiple choice test, reading a longer story for comprehension on a true/false test, decoding a mystery sentence, and completing various vocabulary assessments (word choice, homophones; base/root words, alphabetic order) (range: 0, 1 represents correct responses divided by the number of possible responses). | Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period | 
| Hour 8.75 Packet Activity Decode the Mystery Sentence | Packet Activities: Assessment of ability to organize, listen to instructions, initiate task, complete task, and distractibility, by completing a word search, reading a short story for comprehension on a multiple choice test, reading a longer story for comprehension on a true/false test, decoding a mystery sentence, and completing various vocabulary assessments (word choice, homophones; base/root words, alphabetic order) (range: 0, 1 represents correct responses divided by the number of possible responses). | Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ADHD, Attention Deficit Hyperactivity Disorder