- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00380692
Atomoxetine Versus Placebo for Symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) in Children and Adolescents With Autism Spectrum Disorder
May 5, 2010 updated by: Eli Lilly and Company
A Randomized, Double-blind Comparison of Atomoxetine Hydrochloride and Placebo for Symptoms of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents With Autism Spectrum Disorder
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).
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
97
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Amsterdam, Netherlands, 1100 AL
- 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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Den Haag, Netherlands, 2566 ER
- 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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Groningen, Netherlands, 9713 GZ
- 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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Hoorn, Netherlands, 1624 NP
- 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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Maastricht, Netherlands, 6229 HX
- 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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Nijmegen, Netherlands, 6500 HB
- 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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Oosterhout, Netherlands, 4901 ZG
- 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, 3584 CX
- 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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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
6 years to 17 years (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria (most important):
- ASD (autistic disorder or Asperger's disorder or Pervasive Developmental Disorder - Not Otherwise Specified [PDD NOS])
- Criteria A through D for Attention-Deficit/Hyperactivity Disorder (ADHD)
- At least 1.5 standard deviations above the age norm for their diagnostic subtype using published norms for the ADHD Rating Scale-IV-Parent Version
- Intelligence quotient (IQ) score > 60
Exclusion Criteria (most important):
- weight under 20 kg
- Patients who meet Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) criteria for ASD other than Autistic Disorder, PDD-NOS or Asperger's Disorder;history of Bipolar I or II disorder, schizophrenia, another psychotic disorder, substance abuse;Have a significant medical condition such as heart disease, hypertension, liver or renal failure, pulmonary disease, or seizure disorder identified by history, physical examination, or laboratory tests; Patients who have taken (or are currently taking) anticonvulsants for seizure control.
- patients at serious suicidal risk.
- Contraindication to the use of atomoxetine
- Patients who in the investigator's judgment are likely to need psychotropic medications apart from the drug. Patients who at any time during Study Period II are likely to begin a structured psychotherapy, likely to require hospitalization (i.e. in-patient treatment) or likely to be dismissed from in-patient treatment. Psychotherapy (including hospitalization) initiated at least 2 months prior to study participation is acceptable; however, after study participation has begun, only during Study Period III supportive or educational therapy is permitted.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Atomoxetine
atomoxetine 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
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Other Names:
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Placebo Comparator: Placebo
placebo 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 |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
ADHD Rating Scale-IV-Parent Version: Investigator Scored - Total Score
Time Frame: Baseline and 8 weeks
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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.
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Baseline and 8 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Global Impressions-ADHD-Improvement (CGI-ADHD - I)
Time Frame: 8 weeks, 28 weeks
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Measures total improvement (or worsening) of a patient's ADHD symptoms from the beginning of treatment (1=very much improved, 7=very much worsened).
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8 weeks, 28 weeks
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Conners' Teacher Rating Scale - Revised: Short Form (CTRS-R:S)
Time Frame: Baseline, 8 weeks, 28 weeks
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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.
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Baseline, 8 weeks, 28 weeks
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ADHD Rating Scale-IV-Parent Version: Investigator Scored Total Score
Time Frame: 28 weeks
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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.
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28 weeks
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Sleep Measure Scale
Time Frame: Baseline, 8 weeks, 28 weeks
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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).
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Baseline, 8 weeks, 28 weeks
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Aberrant Behavior Checklist (ABC)
Time Frame: Baseline, 8 weeks, 28 weeks
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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).
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Baseline, 8 weeks, 28 weeks
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Children's Social Behavior Questionnaire (CSBQ) Total Score
Time Frame: Baseline, 8 weeks, 28 weeks
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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.
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Baseline, 8 weeks, 28 weeks
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General Health Questionnaire (GHQ) Total Score
Time Frame: Baseline, 8 weeks, 28 weeks
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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.
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Baseline, 8 weeks, 28 weeks
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Nijmeegse Ouderlijke Stress Index (NOSI) Total Score
Time Frame: Baseline, 8 weeks, 28 weeks
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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.
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Baseline, 8 weeks, 28 weeks
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Amsterdam Neuropsychological Tasks (ANT): Focused Attention Task - Error Rates
Time Frame: Baseline, 8 Weeks
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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.
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Baseline, 8 Weeks
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Amsterdam Neuropsychological Tasks (ANT): Focused Attention Task - Reaction Times for Hits and Correct Rejections
Time Frame: Baseline, 8 Weeks
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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.
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Baseline, 8 Weeks
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Amsterdam Neuropsychological Tasks (ANT): Focused Attention Task - Standard Deviation of Reaction Times for Hits and Correct Rejections
Time Frame: Baseline, 8 Weeks
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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.
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Baseline, 8 Weeks
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Amsterdam Neuropsychological Tasks (ANT): Memory Search Task - Error Rates
Time Frame: Baseline, 8 Weeks
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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.
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Baseline, 8 Weeks
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Amsterdam Neuropsychological Tasks (ANT): Memory Search Task - Reaction Times for Hits and Correct Rejections
Time Frame: Baseline, 8 Weeks
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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.
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Baseline, 8 Weeks
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Amsterdam Neuropsychological Tasks (ANT): Memory Search Task - Standard Deviation (SD) of Reaction Times for Hits and Correct Rejections
Time Frame: Baseline, 8 weeks
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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.
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Baseline, 8 weeks
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Amsterdam Neuropsychological Tasks (ANT): Pursuit Motor Control Task - Accuracy
Time Frame: Baseline, 8 weeks
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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.
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Baseline, 8 weeks
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Amsterdam Neuropsychological Tasks (ANT): Pursuit Motor Control Task - Stability of Movement
Time Frame: Baseline, 8 weeks
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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.
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Baseline, 8 weeks
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Amsterdam Neuropsychological Tasks (ANT): Go/No-Go Response Inhibition Task - Error Rates
Time Frame: Baseline, 8 weeks
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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.
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Baseline, 8 weeks
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Amsterdam Neuropsychological Tasks (ANT): Flanker Interference Task - Error Rates
Time Frame: Baseline, 8 weeks
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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.
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Baseline, 8 weeks
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Amsterdam Neuropsychological Tasks (ANT): Flanker Interference Task - Reaction Times
Time Frame: Baseline, 8 weeks
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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.
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Baseline, 8 weeks
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Cytochrome P450 2D6 Genotype
Time Frame: baseline
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Genotype characterization was used to determine participants' metabolic status.
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baseline
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
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.
- Harfterkamp M, Buitelaar JK, Minderaa RB, van de Loo-Neus G, van der Gaag RJ, Hoekstra PJ. Atomoxetine in autism spectrum disorder: no effects on social functioning; some beneficial effects on stereotyped behaviors, inappropriate speech, and fear of change. J Child Adolesc Psychopharmacol. 2014 Nov;24(9):481-5. doi: 10.1089/cap.2014.0026. Epub 2014 Nov 4.
- van der Meer JM, Harfterkamp M, van de Loo-Neus G, Althaus M, de Ruiter SW, Donders AR, de Sonneville LM, Buitelaar JK, Hoekstra PJ, Rommelse NN. A randomized, double-blind comparison of atomoxetine and placebo on response inhibition and interference control in children and adolescents with autism spectrum disorder and comorbid attention-deficit/hyperactivity disorder symptoms. J Clin Psychopharmacol. 2013 Dec;33(6):824-7. doi: 10.1097/JCP.0b013e31829c764f. No abstract available.
- Harfterkamp M, Buitelaar JK, Minderaa RB, van de Loo-Neus G, van der Gaag RJ, Hoekstra PJ. Long-term treatment with atomoxetine for attention-deficit/hyperactivity disorder symptoms in children and adolescents with autism spectrum disorder: an open-label extension study. J Child Adolesc Psychopharmacol. 2013 Apr;23(3):194-9. doi: 10.1089/cap.2012.0012. Epub 2013 Apr 11.
- Harfterkamp M, van de Loo-Neus G, Minderaa RB, van der Gaag RJ, Escobar R, Schacht A, Pamulapati S, Buitelaar JK, Hoekstra PJ. A randomized double-blind study of atomoxetine versus placebo for attention-deficit/hyperactivity disorder symptoms in children with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2012 Jul;51(7):733-41. doi: 10.1016/j.jaac.2012.04.011. Epub 2012 May 25.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2006
Primary Completion (Actual)
May 1, 2008
Study Completion (Actual)
October 1, 2008
Study Registration Dates
First Submitted
September 22, 2006
First Submitted That Met QC Criteria
September 22, 2006
First Posted (Estimate)
September 26, 2006
Study Record Updates
Last Update Posted (Estimate)
May 11, 2010
Last Update Submitted That Met QC Criteria
May 5, 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
- Dyskinesias
- Attention Deficit and Disruptive Behavior Disorders
- Neurodevelopmental Disorders
- Child Development Disorders, Pervasive
- Disease
- Attention Deficit Disorder with Hyperactivity
- Autistic Disorder
- Autism Spectrum Disorder
- Hyperkinesis
- 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
- 10483 (Other Identifier: CTEP)
- B4Z-UT-S017 (Other Identifier: Eli Lilly and Company)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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