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Atomoxetine Versus Placebo for Symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) in Children and Adolescents With Autism Spectrum Disorder

Phase 4
Completed
Conditions
Attention Deficit Disorder With Hyperactivity
Autistic Disorder
Interventions
Drug: Placebo
Registration Number
NCT00380692
Lead Sponsor
Eli Lilly and Company
Brief Summary

The purpose of this study is to determine whether atomoxetine is effective in reducing ADHD (Attention Deficit/Hyperactivity Disorder) symptoms in children and adolescents with ASD (Autism Spectrum Disorder).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
97
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboplacebo every day (QD), by mouth (PO) for 8 weeks Then patients can take atomoxetine 0.5-1.2 mg/kg/day QD, PO up to 20 weeks
AtomoxetineAtomoxetineatomoxetine 0.5 mg/kg/day every day (QD), by mouth (PO) for 1 week, atomoxetine 0.8mg/kg/day QD, PO for 1 week, 1.2mg/kg/day QD, PO for 6 weeks then atomoxetine 0.5-1.2 mg/kg/day QD, PO for up to 20 weeks
Primary Outcome Measures
NameTimeMethod
ADHD Rating Scale-IV-Parent Version: Investigator Scored - Total ScoreBaseline and 8 weeks

Measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders, Version IV (DSM-IV) diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54.

Secondary Outcome Measures
NameTimeMethod
ADHD Rating Scale-IV-Parent Version: Investigator Scored Total Score28 weeks

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 scores range from 0 to 54.

Clinical Global Impressions-ADHD-Improvement (CGI-ADHD - I)8 weeks, 28 weeks

Measures total improvement (or worsening) of a patient's ADHD symptoms from the beginning of treatment (1=very much improved, 7=very much worsened).

Conners' Teacher Rating Scale - Revised: Short Form (CTRS-R:S)Baseline, 8 weeks, 28 weeks

A 28-item rating scale (0 \[not at all/never\] to 3 \[very much true/very often\]) completed by the teacher to assess problem behaviors related to ADHD. Subscale total scores range from 0 to 15 for Oppositional and Cognitive Problems, 0 to 21 for Hyperactivity, and 0 to 36 for ADHD Index.

Sleep Measure ScaleBaseline, 8 weeks, 28 weeks

10-item parent-based scale assessing sleep problems (6 point Likert scale). Scores: Difficulty falling asleep (1-6); Quality of sleep (3-18); Functional outcome (6-36). Lower scores indicate higher problems with item. Open-ended items: Time to fall asleep (1 \[0-15 minutes\] to 5 \[\>1 hour\]); Total hours (numbers associated with hours of sleep).

Aberrant Behavior Checklist (ABC)Baseline, 8 weeks, 28 weeks

The ABC is a 58-item informant-based scale comprised of five subscales (Irritability \[15 items\], Lethargy \[16\], Stereotypic Behaviors \[7\], Hyperactivity \[16\], Inappropriate Speech \[4\]). Individual item scores range from 0 (no problem) to 3 (severe problem). Subscale scores are total of individual item scores in subscale: Irritability (0-45); Lethargy (0-48); Stereotypic (0-21); Hyperactivity (0-48); Inappropriate Speech (0-12).

Children's Social Behavior Questionnaire (CSBQ) Total ScoreBaseline, 8 weeks, 28 weeks

CSBQ is filled out by parents and consists of 49 items. Items are rated in an ordinal rather than a discrete fashion in order to establish the extent to which problems are present. The CSBQ consists of six subscales. Individual item scores range from 0=does not apply to 2=applies clearly. Total score ranges from 0 to 98.

General Health Questionnaire (GHQ) Total ScoreBaseline, 8 weeks, 28 weeks

Parental distress is measured with the GHQ. The raw total score (based on 0-0-1-1 scoring system) can be used as an overall index of psychological distress, ranging from 0 to 12 with higher scores indicating more distress.

Nijmeegse Ouderlijke Stress Index (NOSI) Total ScoreBaseline, 8 weeks, 28 weeks

The NOSI contains 123 items to be completed by the primary caregiver. Individual item scores range from 1 (completely agree) to 6 (completely disagree). Total scores range from 123 to 738.

Amsterdam Neuropsychological Tasks (ANT): Focused Attention Task - Error RatesBaseline, 8 Weeks

Focused attention assessed distractibility. Child needs to identify a specific target (eg, Cherry); non-target is any other fruit. Child presses "yes" when target occurs in relevant position (eg, one of vertical positions on diamond). Child presses "no" when target is absent, or when target appears on horizontal position (irrelevant target). Error rates are percentage of missing relevant targets and percentage of false alarms in response to (irr)relevant (non)targets based on number of errors/total number of trials X 100.

Amsterdam Neuropsychological Tasks (ANT): Focused Attention Task - Reaction Times for Hits and Correct RejectionsBaseline, 8 Weeks

Task is the same as described in Outcome Measure #10. Reaction times (RT) for hits are mean RTs of correct responses to relevant targets. RTs for correct rejections are mean RTs for correct rejections are mean RTs for correct no responses to irrelevant targets and relevant nontargets.

Amsterdam Neuropsychological Tasks (ANT): Focused Attention Task - Standard Deviation of Reaction Times for Hits and Correct RejectionsBaseline, 8 Weeks

Task is the same as described in Outcome Measure #10. Standard deviations of reaction times (RT) assess intraindividual variability in RT and refer to the same conditions as those for mean reaction times described in Outcome Measure #11.

Amsterdam Neuropsychological Tasks (ANT): Memory Search Task - Error RatesBaseline, 8 Weeks

The memory search task aims at measuring serial search processes to be carried out in working memory. There are 2 blocks (loads) with 40 trials each. Load 1 has 1 target to identify (e.g., an animal). A "yes" is required whenever the target is part of the displayed set of four stimuli (all animals). Load 2 has 2 targets. Whenever 1 of the targets appears in the successively displayed sets of four animals, a "yes" is required. Targets are present in 50% of trials. Error rates are the percentages of errors made in each task condition, based on the number of errors/total number of trials X 100.

Amsterdam Neuropsychological Tasks (ANT): Memory Search Task - Reaction Times for Hits and Correct RejectionsBaseline, 8 Weeks

Memory search task aims at measuring serial search processes to be carried out in working memory. There are 2 blocks (loads) with 40 trials each. Load 1 has 1 target to remember (one animal). A "yes" is required whenever the target is part of displayed set of 4 animals. Load 2 has 2 animals. A "yes" is required whenever one of the animals appears in successively displayed sets of 4 animals. Targets are present in 50% of the trials. Reaction time (RT) for hits is mean RT of correct "yes" responses to targets. RT correct rejections are mean RTs of correct "no" responses when target was missing.

Amsterdam Neuropsychological Tasks (ANT): Memory Search Task - Standard Deviation (SD) of Reaction Times for Hits and Correct RejectionsBaseline, 8 weeks

Task is the same as described in Outcome Measure #14. Standard deviations of reaction times (RT) assess intraindividual variability in RT referring to the two conditions creating hits and correct rejections as mentioned in Outcome Measure #14.

Amsterdam Neuropsychological Tasks (ANT): Pursuit Motor Control Task - AccuracyBaseline, 8 weeks

A complex visuo-motor flexibility task that aims at measuring eye-hand co-ordination and fine motor control. By moving mouse cursor, the child is required to follow as closely as possible a target that randomly moves across the PC-screen. Accuracy is the mean distance between the mouse cursor and the moving target.

Amsterdam Neuropsychological Tasks (ANT): Pursuit Motor Control Task - Stability of MovementBaseline, 8 weeks

A complex visuo-motor flexibility task that measures eye-hand co-ordination and fine motor control. By moving mouse cursor, the child is required to follow as closely as possible a target that randomly moves across the PC-screen. Stability is within subject variability of mean distance between cursor and target.

Amsterdam Neuropsychological Tasks (ANT): Go/No-Go Response Inhibition Task - Error RatesBaseline, 8 weeks

Measures inhibition of pre-potent responses. 24 Go signals (open squares) are presented, randomly mixed with 24 No-Go signals (closed squares). Subjects are required to press a key if a Go signal (target) appears on the screen but to withhold a response if they see a No-Go signal. Error rate is the percentage of key presses to No-Go signals/total number of trials X 100.

Amsterdam Neuropsychological Tasks (ANT): Flanker Interference Task - Error RatesBaseline, 8 weeks

Measures ability to neglect stimuli interfering with predefined stimulus-response coupling. Child presented with displays of 9 colored squares. Child responds to color of central square by pressing left mouse key when blue, and right mouse key when yellow. Part 1 (40 trials), surrounding squares may be same color (compatible) or different (neutral). Part 2 (80 trials), in 50% of trials, surrounding squares have color corresponding to predefined key press for other hand (incompatible). Error rates are percentages of errors in response to compatible and incompatible signals, respectively.

Amsterdam Neuropsychological Tasks (ANT): Flanker Interference Task - Reaction TimesBaseline, 8 weeks

Task is the same as described in Outcome Measure #19. Mean reaction times (RTs) are computed for correct responses to compatible and incompatible flankers, respectively.

Cytochrome P450 2D6 Genotypebaseline

Genotype characterization was used to determine participants' metabolic status.

Trial Locations

Locations (1)

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.

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Utrecht, Netherlands

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