Comparison of Atomoxetine and Placebo in Children With Attention-Deficit/Hyperactivity Disorder (ADHD) and/or Reading Disorder (RD)

Study Overview
=================
Brief Summary
-----------------
To test the hypothesis that a 4 week treatment with atomoxetine is more effective than placebo in patients with combined type Attention Deficit/Hyperactivity Disorder (ADHD), patients with only Reading Disorder, and patients with combined type ADHD and Reading Disorder.

Official Title
-----------------
A Randomized, Double-Blind, Crossover Comparison of Atomoxetine and Placebo in Child Outpatients With Attention-Deficit/Hyperactivity Disorder, Reading Disorder, or Comorbid Attention-Deficit/Hyperactivity Disorder and Reading Disorder.

Conditions
-----------------
Attention Deficit Hyperactivity Disorder, Reading Disorder

Intervention / Treatment
-----------------
* Drug: Atomoxetine Hydrochloride
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical diagnosis with Attention Deficit Hyperactivity Disorder and/or Reading Disorder Exclusion Criteria: Patients with Conduct Disorder Patients who have a history of Bipolar I or II Disorder, psychosis, or Pervasive Development Disorder. Patients who have a current diagnosis of Vocal Tic Disorder, Obsessive Compulsive Disorder, Major Depressive Disorder, Post Traumatic Stress Disorder, Anxiety Disorder, and certain other learning disorders.

Ages Eligible for Study
-----------------
Minimum Age: 8 Years
Maximum Age: 12 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atomoxetine first, then Placebo<br>Atomoxetine, 1.2 mg/kg/day, by mouth (PO) for 4 weeks, 2 week washout period and cross-over to placebo, every day (QD), PO for 4 weeks | Drug: Atomoxetine Hydrochloride<br>* Atomoxetine, 1.2 mg/kg/day, by mouth (PO)<br>* Other names: Strattera;Drug: placebo<br>* Placebo, every day (QD), by mouth (PO)<br>|
| Experimental: Placebo first, then Atomoxetine<br>Placebo, every day (QD), by mouth (PO) for 4 weeks, 2 week washout period and cross-over to atomoxetine 1.2 mg/kg/day, PO for 4 weeks | Drug: Atomoxetine Hydrochloride<br>* Atomoxetine, 1.2 mg/kg/day, by mouth (PO)<br>* Other names: Strattera;Drug: placebo<br>* Placebo, every day (QD), by mouth (PO)<br>|
| No Intervention: Normal Control<br>Normal controls were children selected from the general population. The normal control was matched (have same proportion) by sex (male/female) and by age (have same age range) as the study population. | |
| No Intervention: Reading Disordered Control<br>The reading disordered control group is comprised of children with reading disorder who receive standard remedial teaching therapy. | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stop Signal Reaction Time (SSRT) as Derived From the Stop Signal Reaction Time Paradigm | SSRT measures response execution (go trials) and response inhibition (stop trials). Go trials consist of stimulus (airplane). Child to press response button corresponding to direction airplane is pointing. Stop trials consist of go trial and audible stop signal. Initial delay between go trial and stop signal = 250 msec. If child succeeded in inhibiting response, delay on next stop trial increased by 50 msec, otherwise, delay decreased by 50 msec. SSRT = subtract mean delay from mean go signal reaction time. Lower scores mean better ability to suppress response when presented with stop signal. | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Stop Signal Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset | SSRT measures response execution (go trials) and response inhibition (stop trials). Go trials consist of stimulus (airplane). Child to press response button corresponding to direction airplane is pointing. Stop trials consist of go trial and audible stop signal. Initial delay between go trial and stop signal = 250 msec. If child succeeded in inhibiting response, delay on next stop trial increased by 50 msec, otherwise, delay decreased by 50 msec. SSRT = subtract mean delay from mean go signal reaction time. Lower scores mean better ability to suppress response when presented with stop signal. | Baseline and 4 weeks of therapy | 
| Change From Baseline in Mean Stop Signal Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset | SSRT measures response execution (go trials) and response inhibition (stop trials). Go trials consist of stimulus (airplane). Child to press response button corresponding to direction airplane is pointing. Stop trials consist of go trial and audible stop signal. Initial delay between go trial and stop signal = 250 msec. If child succeeded in inhibiting response, delay on next stop trial increased by 50 msec, otherwise, delay decreased by 50 msec. SSRT = subtract mean delay from mean go signal reaction time. Lower scores mean better ability to suppress response when presented with stop signal. | Baseline and 4 weeks of therapy | 
| Lexical Decision Task Mean Reaction Time: Correct Words | Measure of reaction time to identify whether a word displayed on a computer is a real or correct word versus a pseudo word. During the performance of the lexical decision task that was presented on a computer, the reaction times and accuracy of responses were measured. Data presented are the mean reaction times over the 4 weeks of each therapy for identifying correct words correctly. | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | 
| Lexical Decision Task Mean Reaction Time: Pseudo Words | Measure of reaction time to identify whether a word displayed on a computer is a pseudo word versus a real or correct word. During the performance of the lexical decision task that was presented on a computer, the reaction times and accuracy of responses were measured. Data presented are the mean reaction times over the 4 weeks of each therapy for identifying pseudo words correctly. | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | 
| Working Memory by Corsi Block Tapping Test (CBTT) | Measures the visuo-spatial working memory span, and corresponds to the longest sequence of blocks that has been reproduced correctly at least once. Scores can range from 3 to 8, with the higher score indicating better function. | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | 
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total Score | Measures the 18 symptoms contained in the DSM-IV diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total score is the sum of the scores on the 18 items and range from 0 to 54. | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | 
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Inattention Subscale | Measures the degree of inattention symptoms based on answers to 9 items. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often), for a total Inattention Subscale score range of 0 to 27. | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | 
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Hyperactivity-Impulsivity Subscale | Measures the degree of hyperactivity-impulsivity symptoms, based on answers to 9 items. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often) for a total Hyperactivity-Impulsivity Subscale score of 0 to 27. | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | 
| Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total T-Score | Measures the 18 symptoms contained in the DSM-IV diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total score is computed as the sum of the scores on each of the 18 items. Total score is the sum of the scores on the 18 items and range from 0 to 54. Total T-score = (Total Score - 50)/10. Total T-score ranges from -5 (low severity) to 0.4 (high severity). | Baseline and Week 4 of initial therapy and Week 4 of crossover therapy | 
| Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale | Measures total improvement (or worsening) of a patient's ADHD symptoms from the beginning of treatment (1=very much improved, 7=very much worsened). | 4 week therapy endpoint | 
| Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale | Measures severity of the patient's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients). | 4 week therapy endpoint | 
| Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset: Pseudohomophones | Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudohomophones and pseudo words. Data presented here are for reaction time to identifying psuedohomophones correctly. | Baseline and 4 weeks of therapy | 
| Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset: Pseudo Words | Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudo homophones and pseudo words. Data presented here are for reaction time to identifying pseudo words correctly. | Baseline and 4 weeks of therapy | 
| Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset: Pseudohomophones | Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudo homophones and pseudo words. Data presented here are for reaction time to identifying psuedohomophones correctly. | Baseline and 4 weeks of therapy | 
| Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset: Pseudo Words | Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudo homophones and pseudo words. Data presented here are for reaction time to indentifying pseudo words correctly. | Baseline and 4 weeks of therapy |