Effects of Atomoxetine on Brain Activation During Attention & Reading Tasks in Participants With ADHD & Comorbid Dyslexia

NCT00716274 | Completed Phase 4 Results

• 3 other identifiers: 12212B4Z-US-LYEI2019-000419-98
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

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

Conditions

Attention Deficit Hyperactivity Disorder; Dyslexia

Outcome Measures

Primary Outcomes (6)

• Change From Baseline to Endpoint in Functional Magnetic Resonance Imaging (fMRI) Activation in Participants With Dyslexia Alone (Pseudoword Rhyming and Semantic-category)

  Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) BOLD response (Blood-oxygen-level-dependent response)

  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 fMRI Activation in Participants With Dyslexia Alone (Stroop Attention Tasks)

  Baseline, 16 Weeks

• Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Pseudoword Rhyming and Semantic-category Tasks)

  Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) BOLD response (Blood-oxygen-level-dependent response)

  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 fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Stroop Tasks)

  Baseline, 16 Weeks

• Change From Baseline to Endpoint in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version (ADHDRS) Total Score in the ADHD or ADHD + Dyslexia

  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.

  Baseline, 16 weeks

• Change From Baseline to Endpoint in Woodcock Johnson Tests of Achievement (WJ III) Word Attack Total Score in Participants With Dyslexia Alone

  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.

  Baseline, 16 Weeks

Secondary Outcomes (77)

• 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 BADD-A Total Score in Participants With ADHD or ADHD + Dyslexia

  Baseline, 16 Weeks

• 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 WJ III Individual Test Scores in Participants With ADHD Alone

  Baseline, 16 Weeks

Study Arms (2)

Atomoxetine

EXPERIMENTAL

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.

Drug: Atomoxetine

Placebo

PLACEBO COMPARATOR

Placebo will be packaged in the same way as active comparator to enforce double-blind study design

Drug: Placebo

Interventions

Atomoxetine DRUG

Atomoxetine will be administered at 1.0 to 1.4 mg/kg/day given orally once daily in the morning for 16 weeks

Also known as: LY139603

Atomoxetine

Placebo DRUG

oral, daily, for 16 weeks

Placebo

Eligibility Criteria

• Age: 10 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

Related Links

• Lilly Clinical Trial Registry

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity; Dyslexia

Interventions

Atomoxetine Hydrochloride

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Specific Learning Disorder; Learning Disabilities; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2008
• First Posted: July 16, 2008
• Study Start: September 1, 2008
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: November 4, 2022
• Results First Posted: February 7, 2018

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

US (1)