Clinical trial NCT00380692: Atomoxetine Versus Placebo for Symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) in Children and Adolescents With Autism Spectrum Disorder
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Autistic Disorder
Attention Deficit Disorder With Hyperactivity
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2006-09-26
Enrollment: 97
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: ADHD Rating Scale-IV-Parent Version: Investigator Scored - Total Score
timeFrame: Baseline and 8 weeks
Secondary outcomes:
measure: Clinical Global Impressions-ADHD-Improvement (CGI-ADHD - I)
timeFrame: 8 weeks, 28 weeks
measure: Conners' Teacher Rating Scale - Revised: Short Form (CTRS-R:S)
timeFrame: Baseline, 8 weeks, 28 weeks
measure: ADHD Rating Scale-IV-Parent Version: Investigator Scored Total Score
timeFrame: 28 weeks
measure: Sleep Measure Scale
timeFrame: Baseline, 8 weeks, 28 weeks
measure: Aberrant Behavior Checklist (ABC)
timeFrame: Baseline, 8 weeks, 28 weeks
measure: Children's Social Behavior Questionnaire (CSBQ) Total Score
timeFrame: Baseline, 8 weeks, 28 weeks
measure: General Health Questionnaire (GHQ) Total Score
timeFrame: Baseline, 8 weeks, 28 weeks
measure: Nijmeegse Ouderlijke Stress Index (NOSI) Total Score
timeFrame: Baseline, 8 weeks, 28 weeks
measure: Amsterdam Neuropsychological Tasks (ANT): Focused Attention Task - Error Rates
timeFrame: Baseline, 8 Weeks
measure: Amsterdam Neuropsychological Tasks (ANT): Focused Attention Task - Reaction Times for Hits and Correct Rejections
timeFrame: Baseline, 8 Weeks
measure: Amsterdam Neuropsychological Tasks (ANT): Focused Attention Task - Standard Deviation of Reaction Times for Hits and Correct Rejections
timeFrame: Baseline, 8 Weeks
measure: Amsterdam Neuropsychological Tasks (ANT): Memory Search Task - Error Rates
timeFrame: Baseline, 8 Weeks
measure: Amsterdam Neuropsychological Tasks (ANT): Memory Search Task - Reaction Times for Hits and Correct Rejections
timeFrame: Baseline, 8 Weeks
measure: Amsterdam Neuropsychological Tasks (ANT): Memory Search Task - Standard Deviation (SD) of Reaction Times for Hits and Correct Rejections
timeFrame: Baseline, 8 weeks
measure: Amsterdam Neuropsychological Tasks (ANT): Pursuit Motor Control Task - Accuracy
timeFrame: Baseline, 8 weeks
measure: Amsterdam Neuropsychological Tasks (ANT): Pursuit Motor Control Task - Stability of Movement
timeFrame: Baseline, 8 weeks
measure: Amsterdam Neuropsychological Tasks (ANT): Go/No-Go Response Inhibition Task - Error Rates
timeFrame: Baseline, 8 weeks
measure: Amsterdam Neuropsychological Tasks (ANT): Flanker Interference Task - Error Rates
timeFrame: Baseline, 8 weeks
measure: Amsterdam Neuropsychological Tasks (ANT): Flanker Interference Task - Reaction Times
timeFrame: Baseline, 8 weeks
measure: Cytochrome P450 2D6 Genotype
timeFrame: baseline
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: 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.
city: Den Haag
country: Netherlands
facility: 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.
city: Groningen
country: Netherlands
facility: 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.
city: Hoorn
country: Netherlands
facility: 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.
city: Maastricht
country: Netherlands
facility: 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.
city: Nijmegen
country: Netherlands
facility: 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.
city: Oosterhout
country: Netherlands
facility: 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.
city: Utrecht
country: Netherlands
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.