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
Overview
- Phase
- Phase 4
- Intervention
- Atomoxetine
- Conditions
- Attention Deficit Hyperactivity Disorder
- Sponsor
- Eli Lilly and Company
- Enrollment
- 110
- Locations
- 1
- Primary Endpoint
- Change From Baseline to Endpoint in Functional Magnetic Resonance Imaging (fMRI) Activation in Participants With Dyslexia Alone (Pseudoword Rhyming and Semantic-category)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This study will evaluate the effects of atomoxetine on brain activation during attention and reading tasks via functional Magnetic Resonance Imaging (fMRI) in participants ages 10 to 16 years old with ADHD and comorbid dyslexia
Detailed Description
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 participants with ADHD and comorbid dyslexia. Similar assessments are performed in two additional groups of participants 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants in the ADHD-only or ADHD+dyslexia groups must meet DSM-IV-TR criteria for ADHD
- •Participants in the dyslexia-alone group or ADHD+dyslexia groups must meet criteria for dyslexia
- •Participants must achieve a score of 80 or more on the Full Scale Intelligence Quotient
- •Child or adolescent participants 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
- •Participants for healthy control group do not meet DSM-IV-TR criteria for ADHD and/or dyslexia
- •Participants for healthy control group must achieve a score of at least 80 but not \>120 on the Full Scale Intelligence Quotient
Exclusion Criteria
- •Participants who weigh less than 25.1 kilogram (kg) or greater than 70 kg.
- •Participants with severe allergies to more than 1 class of medications or who have had multiple adverse drug reactions
- •Participants with prior diagnosis of bipolar I or bipolar II disorder or psychosis
- •Participants with documented history of autism, Asperger's syndrome, or pervasive developmental disorder
- •Females who are pregnant or breastfeeding
- •Participants treated with atomoxetine at a therapeutic dose (1.2 mg/kg/day) for at least 4 to 6 weeks
Arms & Interventions
Atomoxetine
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). Participants 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. Participants assigned to atomoxetine during the study period II will be re-randomized to either atomoxetine or placebo whereas participants previously assigned to placebo will receive atomoxetine.
Intervention: Atomoxetine
Placebo
Placebo will be packaged in the same way as active comparator to enforce double-blind study design
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline to Endpoint in Functional Magnetic Resonance Imaging (fMRI) Activation in Participants With Dyslexia Alone (Pseudoword Rhyming and Semantic-category)
Time Frame: Baseline, 16 Weeks
Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) BOLD response (Blood-oxygen-level-dependent response)
Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Pseudoword Rhyming and Semantic-category Tasks)
Time Frame: Baseline, 16 Weeks
Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) BOLD response (Blood-oxygen-level-dependent response)
Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Stroop Tasks)
Time Frame: Baseline, 16 Weeks
Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Stroop Tasks)
Change From Baseline to Endpoint in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version (ADHDRS) Total Score in the ADHD or ADHD + Dyslexia
Time Frame: Baseline, 16 weeks
The ADHDRS-IV-Parent is an 18-item scale with 1 item for each of the 18 symptoms contained in the DSM-IV diagnosis of ADHD. Each item is scored on a 0 to 3 scale: 0=none (never or rarely); 1=mild (sometimes); 2=moderate (often); 3=severe (very often). Total scores range from 0-54. Higher scores indicate higher impairment and lower scores indicate no impairment. LS mean was calculated using a restricted maximum likelihood (REML)-based, MMRM analysis which includes treatment, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.
Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Stroop Attention Tasks)
Time Frame: Baseline, 16 Weeks
Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Stroop Attention Tasks)
Change From Baseline to Endpoint in Woodcock Johnson Tests of Achievement (WJ III) Word Attack Total Score in Participants With Dyslexia Alone
Time Frame: Baseline, 16 Weeks
WJ III (Woodcock et al. 2001) has two parallel forms (A and B) alternating two batteries of tests-Standard and Extended. Standard tests (1 -12) have a broad set of scores. Extended tests (13 -22) have a more in-depth diagnostic assessment of academic strengths and weaknesses. Tests administered were 1, 2, 7, 9, 13, 17, and 20. The standard score scale is a mean (M) of 100 and a standard deviation (SD) of 15. The WJ III ACH has extended standard scores which is a greater range of standard scores. Test 13, Word Attack, measures skill in applying phonic, structural analysis to the pronunciation of unfamiliar printed words. Each individual test scores range from 0 to over 200 where 69 and below is very low and 131 and above is very superior. Higher scores indicate better reading skills. Least Square (LS) Mean was analyzed using last observation carried forward (LOCF), fixed-effects analysis of covariate (ANCOVA) models with terms for treatment, gender, baseline, age, treatment\*baseline.
Secondary Outcomes
- Change From Baseline to Endpoint in BADD-A Total Score in Participants With ADHD or ADHD + Dyslexia(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in Basic Reading Skills Cluster WJ III in Participants With Dyslexia Alone(Baseline, 16 Weeks)
- Change From Baseline to Endpoint in GORT-4 in Participants With ADHD Alone(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in CTOPP Composite Score in Participants With ADHD + Dyslexia(Baseline, 16 weeks)
- Change From Baseline to Endpoint in Working Memory Test Battery for Children (WMTB-C) in Participants With Dyslexia Alone(Baseline, 16 Weeks)
- Change From Baseline to Endpoint in Comprehensive Test of Phonological Processing (CTOPP) Composite Scores in Participants With Dyslexia Alone(Baseline, 16 weeks)
- Change From Baseline to Endpoint in Gray Oral Reading Tests-4 (GORT-4) in Participants With Dyslexia Alone(Baseline, 16 weeks)
- Change From Baseline to Endpoint in GORT-4 in Participants With ADHD + Dyslexia(Baseline, 32 Weeks)
- Change From Baseline to Endpoint WMTB-C in Participants With ADHD + Dyslexia(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in ADHDRS-IV Total Score in Participants With Dyslexia Alone(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in WJ III Individual Test Scores in Participants With Dyslexia Alone(Baseline, 16 Weeks)
- Change From Baseline to Endpoint in WJ III Individual Test Scores in Participants With ADHD + Dyslexia(Baseline, 16 Weeks)
- Change From Baseline to Endpoint in CTOPP Composite Score in Participants With ADHD Alone(Baseline, 16 weeks)
- Change From Baseline to Endpoint in WJ III Individual Scores in Participants With Dyslexia Alone(From Week 16, Up to 32 Weeks)
- Change From Baseline to Endpoint in WJ III Individual Test Scores in Participants With ADHD Alone(Baseline, 16 Weeks)
- Change From Baseline to Endpoint Test of Word Reading Efficiency (TOWRE) Total Score in Participants With Dyslexia Alone(Baseline, 16 Weeks)
- Change From Baseline to Endpoint in TOWRE Total Score in Participants With ADHD or ADHD + Dyslexia(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in WJ III Individual Scores in Participants With ADHD Alone(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in Participants in WMTB-C With Dyslexia Alone(Baseline, 32 Weeks)
- Change From Baseline to Endpoint WMTB-C in Participants With ADHD Alone(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in BADD-A Total Score in Participants With Dyslexia Alone(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in WJ III Individual Scores in Participants With ADHD + Dyslexia(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in CTOPP Composite Scores in Participants With ADHD Alone(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in Participants in TOWRE Total Score With Dyslexia Alone(Baseline, 32 Weeks)
- Change From Baseline to Endpoint in CTOPP Composite Scores in Participants With ADHD + Dyslexia(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Stroop Tasks)(From Week 16, Up to 32 Weeks)
- Change From Baseline to Endpoint in ADHDRS-IV-Parent: Inv Total Score in Participants With ADHD or ADHD + Dyslexia(From Week 16, Up to Week 32)
- The Number of Participants With Treatment Emergent Adverse Events (TEAE) in Participants With Dyslexia(16 Weeks)
- Change From Baseline to Endpoint in CTOPP Composite Scores in Participants With Dyslexia Alone(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in GORT-4 in Participants With Dyslexia Alone(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in ADHDRS-IV-Parent: Inv Total Score in Participants With ADHD or ADHD +Dyslexia(Baseline, 32 Weeks)
- Change From Baseline to Endpoint in WMTB-C in Participants With Dyslexia Alone(From Week 16, Up to Week 32)
- The Number of Participants With TEAE in Participants With Dyslexia(From 16 Weeks Up to Week 32)
- Change From Baseline to Endpoint in Participants in TOWRE Total Score With ADHD or ADHD + Dyslexia(Baseline, 32 Weeks)
- Change From Baseline to Endpoint TOWRE Total Score in Participants With Dyslexia Alone(From Week 16, Up to Week 32)
- The Number of Participants With TEAE in Participants With ADHD or ADHD+Dyslexia.(From Week 16 Up to Week 32)
- Change From Baseline to Endpoint in WJ III Individual Scores in Healthy Participants(Baseline, 32 Weeks)
- Change From Baseline to Endpoint in Participants in WMTB-C With ADHD + Dyslexia(Baseline, 32 Weeks)
- Change From Baseline to Endpoint in Participants in WMTB-C With ADHD Alone(Baseline, 32 Weeks)
- Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Pseudoword Rhyming, Semantic-category)(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Stroop Tasks)(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in GORT-4 in Participants With ADHD+ Dyslexia(From Week 16, Up to Week 32)
- Number of Participants With Adverse Events(32 Weeks)
- Change From Baseline to Endpoint in CTOPP Composite Scores in Healthy Participants(Baseline, 32 weeks)
- Change From Baseline to Endpoint in GORT-4 in Healthy Participants(Baseline, 32 Weeks)
- Change From Baseline to Endpoint in ADHDRS-IV-Parent: Inv Total Score in Participants With Dyslexia Alone(Baseline, 32 Weeks)
- Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Pseudoword Rhyming and Semantic-category Tasks)(From Week 16, Up to Week 32)
- Change From Baseline to Endpoint in ADHDRS-IV Total Score in Healthy Participants(Baseline, 16 Weeks)
- Change From Baseline to Endpoint in TOWRE Total Score in Healthy Participants(Baseline, 32 Weeks)
- Change From Baseline to Endpoint TOWRE Total Score in Healthy Participants(Baseline, 16 Weeks)
- Change From Baseline to Endpoint in WMTB-C in Healthy Participants(Baseline, 32 Weeks)
- Change From Baseline to Endpoint in ADHDRS-IV-Parent: Inv Total Score in Healthy Participants(Baseline, 32 Weeks)
- Change From Baseline to Endpoint in BADD-A Total Score in Healthy Participants(Baseline, 32 Weeks)