Official Title: “Neurophysiology of Attention-Deficit/Hyperactivity Disorder (ADHD) and Comorbid Dyslexia: Functional Magnetic Resonance Imaging (fMRI) Measures of Brain Activation During Attention and Reading Tasks Pre- and Post-Atomoxetine Treatment”

This study will evaluate the effects of atomoxetine on brain activation during attention and reading tasks via functional Magnetic Resonance Imaging (fMRI) in patients ages 10 to 16 years old with ADHD and comorbid dyslexia

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: April 2012

This is a randomized, placebo-controlled, double-blind, single site study that uses an fMRI measurement to assess brain activation during attention and reading tasks and the effects of atomoxetine in reducing symptoms of ADHD in patients with ADHD and comorbid dyslexia. Similar assessments are performed in two additional groups of patients with ADHD only and dyslexia only to determine to what extent symptomatic change in the comorbid ADHD & dyslexia is achieved independently by atomoxetine effects on either condition. A healthy control group of non-ADHD, non-dyslexia subjects (20) will be included to monitor practice effects & effects of treatment that may be interpreted as normal maturation. The healthy control group will not be treated with any study medications.

Intervention(s) in this Clinical Trial

• Drug: Atomoxetine
  • Atomoxetine will be administered at 1.0 to 1.4 mg/kg/day given orally once daily in the morning for 32 weeks
• Drug: Placebo
  • oral, daily, for 32 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Atomoxetine will be administered at 1.0 to 1.4 mg/Kg/day given orally once daily in the morning for 16 weeks (study period II). Patients who complete the study period II will be re-randomized in the study period III of 16-week duration to assess maintenance of benefit following discontinuation of treatment with atomoxetine. Patients assigned to atomoxetine during the study period II will be re-randomized to either atomoxetine or placebo whereas patients previously assigned to placebo will receive atomoxetine.
• Placebo Comparator: 2
  • Placebo will be packaged in the same way as active comparator will to enforce double-blind study design

Primary Measures

• To assess the effect of atomoxetine on brain activation pattern during attention & reading tasks in children & adolescents with ADHD & comorbid dyslexia and ADHD alone.
  • Time Frame: 16 weeks
    Safety Issue?: No

Secondary Measures

• To assess the correlation between the patterns of brain activation, measured via fMRI, & the clinical findings (ADHDRS & reading scores) in the ADHD alone group & in ADHD with comorbid dyslexia group.
  • Time Frame: 16 weeks
    Safety Issue?: No
• To assess the effect of atomoxetine on brain activation patterns as patients perform the Stroop attention task, pseudoword rhyming, and semantic-category tasks during fMRI in patients with ADHD alone compared to patients with ADHD & comorbid dyslexia.
  • Time Frame: 16
    Safety Issue?: No
• To assess brain activation patterns during fMRI as patients perform the Stroop attention task, pseudoword rhyming, & semantic-category tasks in patients with ADHD alone compared with healthy control subjects.
  • Time Frame: 16 weeks
    Safety Issue?: No
• To assess brain activation patterns during fMRI as patients perform the Stroop attention task, pseudoword rhyming, & semantic-category tasks in patients with ADHD & comorbid dyslexia compared with healthy control subjects.
  • Time Frame: 16 weeks
    Safety Issue?: No
• To assess Basic Reading, fluency, comprehension, & spelling skills as measured by Woodcock Johnson III in patients with ADHD alone & ADHD plus comorbid dyslexia.
  • Time Frame: 16 weeks, atomoxetine versus placebo; 32 weeks atomoxetine
    Safety Issue?: No
• To assess phonological processing as measured by the Comprehensive Test of Phonological Processing in patients with ADHD alone & ADHD plus comorbid dyslexia.
  • Time Frame: 16 weeks, atomoxetine versus placebo; 32 weeks atomoxetine
    Safety Issue?: No
• To assess oral reading rate, accuracy, fluency, and comprehension, and overall reading performance as measured by the Gray Oral Reading Tests-4 & Test of Word Reading Efficiency in patients with ADHD alone & ADHD plus comorbid dyslexia.
  • Time Frame: 16 weeks, atomoxetine versus placebo; 32 weeks atomoxetine
    Safety Issue?: No
• To assess working memory & executive functioning as measured by WMTB-C & Brown Attention-Deficit Disorder Scale-Adolescent Version (BADD-A), respectively in patients with ADHD alone & ADHD plus comorbid dyslexia.
  • Time Frame: 16 weeks, atomoxetine versus placebo; 32 weeks atomoxetine
    Safety Issue?: No
• To evaluate maintenance of benefit after discontinuation of treatment with atomoxetine in patients who were previously assigned to atomoxetine during the acute treatment period. These patients will be re-randomized to atomoxetine or placebo.
  • Time Frame: 16 weeks
    Safety Issue?: No
• To assess safety & tolerability of atomoxetine in the ADHD alone group, ADHD with comorbid dyslexia group, & dyslexia alone group as assessed by laboratory, vitals, ECG measures, & adverse events collection.
  • Time Frame: 16 & 32 weeks
    Safety Issue?: Yes

Inclusion Criteria:

• Patients must meet DSM-IV-TR criteria for ADHD
• Patient must meet DSM-IV-TR criteria for dyslexia
• Patients must achieve a score of 80 or more on the Full Scale Intelligence
• Quotient
• Child or adolescent patients must be 10 to 16 years old
• Must be able to communicate in English
• Must be able to swallow capsules
• Be reliable to keep appointments for clinic visits & all related tests
• Subjects for healthy control group do not meet DSM-IV-TR criteria for AHHD and/or dyslexia
• Subjects for healthy control group must achieve a score of at least 80 but not >120 on the Full Scale Intelligence Quotient

Exclusion Criteria:

• Patients who weigh less than 25 kg or greater than 70 kg
• Patients with severe allergies to more than 1 class of medications or who have had multiple adverse drug reactions
• Patients with prior diagnosis of bipolar I or bipolar II disorder or psychosis
• Patients with documented history of autism, Asperger's syndrome, or pervasive developmental disorder
• Females who are pregnant or breastfeeding
• Patients treated with atomoxetine at a therapeutic dose (1.2 mg/kg/day) for at least 4 to 6 weeks

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 10 Years

Maximum Age for this Clinical Trial: 16 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Eli Lilly and Company

Overall Clinical Trial Officials and Contacts

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

Overall Contact: There is only one site for this clinical trial 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00716274

Study ID Number: 12212

ClinicalTrials.gov Identifier: NCT00716274

Health Authority: United States: Food and Drug Administration

Lilly Clinical Trial Registry