Atomoxetine, Placebo and Parent Management Training in Autism

Study Overview
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Brief Summary
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The study will evaluate the effectiveness of atomoxetine (Strattera) with and without Parent Management Training (PMT) in children with Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDDNOS) who have symptoms of Attention Deficit Hyperactivity Disorder (ADHD). This is a double-blind placebo, parallel study where the atomoxetine will have a dose titration over a 6 week period. All children will be seen weekly during this titration period, with additional visits at Week 8 and Week 10. Families assigned to the PMT arm will have an additional weekly meeting with a clinician for a total of 9 PMT visits. PMT involves teaching parents to implement behavioral interventions with their children. Subjects who are clinical responders (ADHD Responders and Compliance Responders) from the 10 week study period will be followed every 4 weeks in a 24-week extension study. Subjects who are clinical nonresponders will continue in PMT if they received PMT during the double-blind phase, and they will receive an open trial of atomoxetine if they were on placebo during the double-blind phase. All subjects (responders and nonresponders) will be invited to participate in follow-up assessments every 4 weeks for 24 weeks after the completion of the double-blind phase.

Official Title
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Atomoxetine, Placebo and Parent Management Training in Autism

Conditions
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Autism, Pervasive Development Disorder, Asperger's Disorder, Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: atomoxetine
* Drug: Placebo
* Behavioral: Parent Management Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children 5 yrs to 14 years 11 mos with clinical diagnosis of Autism, Asperger's Disorder, or PDDNOS based upon the ADI-R and clinical evaluation by DSM-IV criteria, Mental age equal to or greater than 24 months, ADHD symptoms based upon the CASI and clinical confirmed diagnosis, CGIS-S rating of 4 or grater for ADHD symptoms, A mean item score of >1.5 on both the Parent and Teacher (non-parent caregiver) SNAP-IV 18 ADHD symptoms or the 9-symptom hyperactive-impulsive subscale (symptoms must be cross-situational), Reliable care provider available to bring subject to clinic visits and weekly sessions. Exclusion Criteria: DSM-IV diagnosis of schizophrenia, schizoaffective disorder psychotic disorder NOS,bipolar disorder, or major depression (if accompanied by a family history of bipolar disorder) based upon evidence of suicidality, CASI, and clinical interview/history, Prior failed adequate trial of atomoxetine, Use of other psychotropic medications that produce CNS effects, Diagnosis of bipolar disorder, major depression, hypertension, cardiovascular disease, narrow angle glaucoma, other significant physical illness, Pregnancy or sexually active females (intercourse in the past 6 months, reported by either the subject or caregiver), Currently on effective medication treatment for ADHD, Prior involvement in Parent Management Training or other similar program, Currently on albuterol or taking beta blockers, Taking supplements or other complementary medical treatments where dose cannot be held at current level for duration of study

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Atomoxetine + Parent Management Training | Drug: atomoxetine<br>* atomoxetine<br>Behavioral: Parent Management Training<br> <br> |
| Active Comparator: 2<br>Atomoxetine without Parent Management Training | Drug: atomoxetine<br>* atomoxetine<br>|
| Placebo Comparator: 3<br>Placebo + Parent Management Training | Drug: Placebo<br>* Placebo + parent management treatment<br>Behavioral: Parent Management Training<br> <br> |
| Placebo Comparator: 4<br>Placebo without Parent Management Training | Drug: Placebo<br>* Placebo + parent management treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Were Attention Deficit Hyperactivity Disorder (ADHD) Respondents | Respondents were defined as having ≥30% decrease on the SNAP and CGI-I<=2). The Swanson, Nolan, and Pelham (SNAP)-IV Parent and Teacher Rating Scales were used to measure ADHD and oppositional symptoms at home and school. The SNAP-IV ADHD section contains items for each of the 18 Diagnostic and Statistical Manual of Mental Disorders-IV symptoms of ADHD rated from 0 (not at all) to 3 (very much). The Clinical Global Impressions Scale (CGI) includes subscales for severity of illness and global improvement. The Severity scale is scored from 1 (normal) to 7 (extremely ill), with a rating of ≥4 required for inclusion. The Improvement score ranged from 1 (very much improved) through 4 (no change) to 7 (very much worse). The CGI was completed by a blinded rater based on parent/child interview and review of completed parent and school behavior problem questionnaires at each study visit. | week 10 | 
| Percentage of Participants Who Were Autism Spectrum Disorder Respondents | Respondents were defined as having ≥30% decrease on the HSQ and CGI-I≤2). The 25-item HSQ was adapted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate behavioral noncompliance in children with autism spectrum disorder (ASD). The Home Situations Questionnaire - Pervasive Developmental Disorder (HSQ) is a 25-item parent rating scale assessing noncompliance. Parents are asked to indicate whether each item is a problem and, if so, its severity from 1 (mild) to 9 (severe). The School Situations Questionnaire (SSQ) is a 9-item teacher rating scale that assesses noncompliance. The SSQ is a companion instrument to the HSQ and uses the same rating scale. The Clinical Global Impressions Scale (CGI) includes subscales for severity of illness and global improvement. The Severity scale is scored from 1 (normal) to 7 (extremely ill), | week 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism, PDD NOS, Attention Deficit Hyperactivity Disorder, Parent Management Training