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

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.

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.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder; Reading Disorder
• Intervention / Treatment: Drug: Atomoxetine Hydrochloride; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Netherlands
  • Almere, Netherlands, 1311 RL
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Amsterdam, Netherlands, 1081 BT
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Breda, Netherlands, 4819 EV
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Vught, Netherlands, 5260 GB
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atomoxetine first, then Placebo; 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; Atomoxetine, 1.2 mg/kg/day, by mouth (PO); Other Names: LY139603; Strattera; Drug: placebo; Placebo, every day (QD), by mouth (PO)
Experimental: Placebo first, then Atomoxetine; 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; Atomoxetine, 1.2 mg/kg/day, by mouth (PO); Other Names: LY139603; Strattera; Drug: placebo; Placebo, every day (QD), by mouth (PO)
No Intervention: Normal Control; 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; 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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 . Mon-Fri 9AM - 5PM Eastern Time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

General Publications

• Bangs ME, Wietecha LA, Wang S, Buchanan AS, Kelsey DK. Meta-analysis of suicide-related behavior or ideation in child, adolescent, and adult patients treated with atomoxetine. J Child Adolesc Psychopharmacol. 2014 Oct;24(8):426-34. doi: 10.1089/cap.2014.0005. Epub 2014 Jul 14.
• de Jong CG, Van De Voorde S, Roeyers H, Raymaekers R, Allen AJ, Knijff S, Verhelst H, Temmink AH, Smit LM, Rodriques-Pereira R, Vandenberghe D, van Welsen I, ter Schuren L, Al-Hakim M, Amin A, Vlasveld L, Oosterlaan J, Sergeant JA. Differential effects of atomoxetine on executive functioning and lexical decision in attention-deficit/hyperactivity disorder and reading disorder. J Child Adolesc Psychopharmacol. 2009 Dec;19(6):699-707. doi: 10.1089/cap.2009.0029.

Helpful Links

• Lilly Clinical Trial Registry

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 19, 2005

Study Record Updates

• Last Update Posted (Estimate): May 25, 2010
• Last Update Submitted That Met QC Criteria: May 17, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Language Disorders; Communication Disorders; Learning Disabilities; Disease; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Dyslexia; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride
• Other Study ID Numbers: 7955 (CTEP); B4Z-MC-LYCK (Other Identifier: Eli Lilly and Company)