Official Title: “Atomoxetine, Placebo, and Parent Training in Autism”

This study will evaluate the effectiveness of the medication atomoxetine, with and without parent management training, in treating children with autism or pervasive developmental disorder not otherwise specified who have symptoms of attention deficit hyperactivity disorder.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: April 2013

Autism and pervasive developmental disorder not otherwise specified (PDDNOS), an autism spectrum disorder, are brain development disorders characterized by abnormalities in communication, social interactions, and range of interests. Overactivity and inattention, both symptoms of attention deficit hyperactivity disorder (ADHD), are commonly reported among children with autism. Recent data have suggested that at least 14% of children with autism are treated for ADHD symptoms, typically with stimulant medication. However, response rates to stimulant medication are poorer among children with autism than among typically developing children with ADHD, suggesting a substantial need for potential alternative treatment options. Previous studies have shown that training programs that teach parents ways to address adaptive behavior and behavioral problems can be effective in improving symptoms of autism and ADHD in children. Parent training, in combination with the nonstimulant ADHD medication atomoxetine, may be the best way to improve emotional and attention-related problems in children with autism and ADHD. This study will evaluate the effectiveness of the medication atomoxetine, with and without parent management training (PMT), in treating children with autism or PDDNOS who have symptoms of ADHD.

Participation in this study will last 9 months and will include two phases. Phase 1 will last 12 weeks. After screening, all eligible child participants will undergo baseline assessments that will include tests of attention and/or memory on a computer system, vital sign measurements, and a review of past medications. Parent participants will also complete questionnaires about their child's behavior and symptoms and a review of any previous parent training experiences.

Participants will then be assigned randomly to one of four treatment groups: atomoxetine plus PMT, atomoxetine alone, placebo plus PMT, or placebo alone. Child participants will take their assigned study medication twice daily for 10 weeks and will attend weekly clinic visits. During these visits, child participants will undergo vital sign measurements, possible medication adjustments, and some of the baseline learning testing. Parent participants will be asked questions about their child's side effects and behavior.

Participants assigned to also receive PMT will individually meet with a clinician weekly for 10 weeks. The sessions involving a parent and child or parent alone will include parenting instruction, practice activities, behavior rehearsal with feedback from the behavior therapist, and role-playing of specific skills. Parents will also be given at-home homework assignments that will involve practicing techniques learned in sessions and collecting information on their child's behavior. At the end of Phase 1, all participants will repeat the baseline assessments and children will undergo a physical exam.

Any child participants who have shown improvement after Phase 1 will be invited to participate in Phase 2, which will last 24 weeks. Child participants will continue to take their assigned medications from Phase 1 and, if applicable, will continue PMT sessions once a month. They will attend 6 monthly clinic visits that will involve the same procedures conducted in Phase 1 visits. Upon completing the 24 additional weeks of treatment, all participants will undergo repeat baseline assessments.

Intervention(s) in this Clinical Trial

• Drug: Atomoxetine
  • Child participants will take atomoxetine twice a day for 10 weeks. The dose will be increased gradually for the first 6 weeks, based on the child's response to side effects. If the child shows improvement after the initial 10 weeks of treatment, atomoxetine treatment will be continued twice daily for 24 more weeks.
• Behavioral: Parent management training (PMT)
  • PMT will include individual parent sessions held weekly for 10 weeks. Some sessions will include both parent and child. Sessions will include parenting instruction, practice activities, behavior rehearsal with feedback from the behavior therapist, and role-playing of specific skills. If child participants show improvement after the initial 10 weeks of treatment, monthly PMT sessions will continue for 24 more weeks.
• Drug: Placebo
  • Child participants will take placebo twice a day for 10 weeks. If the child shows improvement after the initial 10 weeks of treatment, placebo treatment will be continued twice daily for 24 more weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Participants will receive treatment with atomoxetine plus parent management training.
• Active Comparator: 2
  • Participants will receive treatment with atomoxetine only.
• Placebo Comparator: 3
  • Participants will receive treatment with placebo plus parent management training.
• Placebo Comparator: 4
  • Participants will receive treatment with placebo only.

Primary Measures

• Effectiveness of atomoxetine versus placebo in treating children with autism or PDDNOS who exhibit symptoms of ADHD; Parent-rated Swann Nolan and Pelham Questionnaire (SNAP-IV)
  • Time Frame: Measured at Week 10 and Week 24 of extension phase
    Safety Issue?: Yes
• Effectiveness of parent management versus no parent management compliance
  • Time Frame: Measured at Week 10 and Week 24 of extension phase
    Safety Issue?: No
• Home and School Situations Questionnaires and the Standardized Observation Assessment Procedure
  • Time Frame: Measured at Week 10 and Week 24 of extension phase
    Safety Issue?: No

Secondary Measures

• Clinical Global Impressions CGI) - Improvement and severity
  • Time Frame: Measured at Week 10 and Week 24 of extension phase
    Safety Issue?: No
• Teacher-rated SNAP-IV
  • Time Frame: Measured at Week 10 and Week 24 of extension phase
    Safety Issue?: No
• Parent- and teacher-rated Aberrant Behavior Checklists (ABCs)
  • Time Frame: Measured at Week 10 and Week 24 of extension phase
    Safety Issue?: No
• CGI Severity Adverse Events Questionnaire
  • Time Frame: Measured at Week 10 and Week 24 of extension phase
    Safety Issue?: Yes
• Vital signs (blood pressure, pulse, height, weight)
  • Time Frame: Measured at Week 10 and Week 24 of extension phase
    Safety Issue?: No
• Labs (electrocardiogram, urinalysis, complete blood count, liver function tests)
  • Time Frame: Measured at Week 10 and Week 24 of extension phase
    Safety Issue?: No
• Cognitive performance (Continuous Performance Test, Delay of Gratification, Speeded Classification Test, Cancellation Task)
  • Time Frame: Measured at Week 10 and Week 24 of extension phase
    Safety Issue?: No
• Parenting Stress Index (Short Form)
  • Time Frame: Measured at Week 10 and Week 24 of extension phase
    Safety Issue?: No
• Parent Treatment Preference Questionnaire
  • Time Frame: Measured at Week 10 and Week 24 of extension phase
    Safety Issue?: No

Inclusion Criteria:

• Child is 5 years to 13 years 11 months old and has a clinical diagnosis of autism or PDDNOS on the basis of the Autism Diagnostic Interview-Revised (ADI-R) and clinical evaluation by Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria
• IQ of at least 35
• ADHD symptoms based upon the SNAP-IV, Diagnostic Interview for Children and Adolescents IV (DICA-IV) and clinically confirmed diagnosis
• Clinical Global Impressions-Severity Scale (CGISS) rating of 4 or greater for ADHD symptoms
• Reliable care provider available to bring child to clinic visits and weekly PMT sessions

Exclusion Criteria:

• DSM-IV diagnosis of Asperger's syndrome, schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified (based upon DICA-IV)
• Prior failed adequate trial of atomoxetine
• Use of other psychotropic medications that produce central nervous system effects
• Diagnosis of bipolar disorder or major depression
• Diagnosis of high blood pressure, cardiovascular disease, narrow angle glaucoma, or other significant physical illness
• Pregnant or sexually active female (intercourse in the 6 months before study entry)
• Currently taking effective medication treatment for ADHD
• Prior involvement in structured PMT or other similar program
• Currently on albuterol or taking beta blockers

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 5 Years

Maximum Age for this Clinical Trial: 14 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Mental Health (NIMH)

Overall Clinical Trial Officials and Contacts

Benjamin Handen, PhD Principal Investigator University of Pittsburgh  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00699205

Study ID Number: R01 MH079082

ClinicalTrials.gov Identifier: NCT00699205

Health Authority: United States: Food and Drug Administration