Official Title: “Targeted Pharmacologic Interventions for Autism: A Double-Blind, Placebo-Controlled Trial of Atomoxetine in Children and Adolescents With Autism”

This study will evaluate the effectiveness of atomoxetine in treating children with attention deficit hyperactivity disorder symptoms associated with autistic disorder, Asperger's syndrome, and pervasive developmental disorder, not otherwise specified.

Study Type: Interventional

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

Study Primary Completion Date: July 2012

Autism is a developmental disorder that can cause severe and pervasive impairment in thinking, feeling, language, and the ability to relate to others. It is usually first diagnosed in early childhood. Children with autism demonstrate repetitive behaviors or interests and deficits in social interaction, verbal communication, and nonverbal communication. In addition, they often have unusual responses to sensory experiences, such as certain sounds or the way objects look. Some symptoms of attention deficit hyperactivity disorder (ADHD), such as inattention, hyperactivity, and impulsivity, are also associated with autism. Atomoxetine is a selective norepinephrine reuptake inhibitor that is used to treat ADHD. It works differently, however, than stimulant drugs and may help to reduce ADHD symptoms in children with autism. This study will evaluate the effectiveness of atomoxetine in treating children with ADHD symptoms associated with autism.

Potential participants will first attend a screening visit, which will include a psychiatric diagnostic interview, a practice session for swallowing pill capsules, a physical exam, an electrocardiogram (ECG), a blood test, and an assessment of pubertal stage. Females of childbearing age will also undergo a urine pregnancy test. In an initial double-blind study phase, eligible participants will be randomly assigned to receive either atomoxetine or placebo for 8 weeks. A baseline visit will include several rating scales, observations, and an interview to assess adaptive functioning. These measures and procedures will be used to keep track of symptoms, side effects, and behavior that could change during the study.

Children who are assigned to placebo and do not notice an improvement in their ADHD symptoms will be given the opportunity to receive atomoxetine at the end of 8 weeks. Study visits will occur once a week for 4 weeks, and then every other week for the remainder of the 8 weeks.

During these visits, many of the baseline questionnaires and interviews will be repeated. At the Week 8 visit, the physical exam, ECG, blood tests, and some baseline questionnaires will also be repeated. All children who respond well to atomoxetine may continue taking the drug for an additional 10 months. During this time, participants will report to the clinic once a month for the first 4 months, then once at the end of 7 months, and finally once at the end of 10 months. The same measures and procedures that were done during the 8-week phase will be done during the 10-month phase of this study.

Intervention(s) in this Clinical Trial

• Drug: Atomoxetine
  • Available tablet strengths of atomoxetine: 5 mg, 10 mg, 25 mg, 40 mg. Week 1 participant takes 0.5 mg/kg/day, Week 2: 0.8 mg/kg/day, Week 3: 1.2 mg/kg/day. Potential exists for dose increase at Week 4 to 1.8 mg/kg/day based on clinical global impression-improvement rating at Week 4.
• Drug: Placebo
  • Placebo tablets dosages: 5 mg, 10 mg, 25 mg, 40 mg.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Participants will receive atomoxetine for 8 weeks
• Placebo Comparator: 2
  • Participants will receive placebo for 8 weeks

Primary Measures

• ADHD symptoms
  • Time Frame: Measured at Weeks 1 through 4, 6, and 8
    Safety Issue?: No

Secondary Measures

• Irritability and anxiety
  • Time Frame: Measured at Weeks 1 through 4, 6, and 8
    Safety Issue?: Yes
• Core autistic symptoms
  • Time Frame: Measured at Weeks 1 through 4, 6, and 8
    Safety Issue?: No
• Quality of life
  • Time Frame: Measured at Weeks 1 through 4, 6, and 8
    Safety Issue?: No

Inclusion Criteria:

• Diagnosis of an autism spectrum disorder (autistic disorder, Asperger's syndrome, and pervasive developmental disorder, not otherwise specified).
• Significant hyperactivity, inattention, or impulsivity as determined by a score on an investigator-administered ADHD Rating Scale (ADHDRS)-Home Version that is at least 1.5 standard deviations above the mean for age and sex
• Parent/caregiver's primary complaint about the child is inattention, hyperactivity, and/or impulsivity ("ADHD" symptoms)
• Symptoms present for 6 months prior to study entry
• Psychotropic drug-free for at least 2 weeks prior to starting study medication. This drug-free period will be 5 weeks for fluoxetine (Prozac).

Exclusion Criteria:

• Weighs less than 15 kg (about 33 pounds)
• Any another psychiatric disorder that may require a different treatment, including psychotic disorders, major affective disorders, obsessive-compulsive disorder, panic disorder, or substance-related disorders
• DSM-IV diagnosis of Rett's disorder or childhood disintegrative disorder
• Presence of extreme aggression or self-injury
• Currently taking an effective psychotropic drug
• Currently using other medications that may be unsafe to take with atomoxetine (e.g., potent CYP 2D6 inhibitors, intravenous albuterol, monoamine oxidase [MAO] inhibitors)
• Inability to swallow study medication
• Presence of a medical condition that would make treatment with atomoxetine unsafe (e.g., unstable hypertension or cardiac disease, asthma requiring frequent treatment with albuterol, narrow angle glaucoma, pregnancy, etc.)
• Mental age of less than 18 months
• Previous adequate trial of atomoxetine
• Previous evidence of hypersensitivity or an allergic reaction to atomoxetine
• Clinically significant abnormalities in laboratory measures indicating an undiagnosed medical condition as determined by the study physician in discussion with the participant's primary care physician
• Clinically significant abnormalities on ECG as determined by a pediatric cardiologist
• Pregnant
• Initiation of a new psychosocial intervention within 90 days prior to starting study medication. Participants who have recently had a significant change in their psychosocial interventions will not be eligible until this intervention has been stable for 90 days in order to avoid confounding results of the study. Stable interventions (e.g., speech and occupational therapy) will be allowed to continue during the course of the study. Minor changes in ongoing treatment (e.g., missed therapy sessions due to holiday/vacation planned break in therapy due to school holidays) will not be considered significant.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 6 Years

Maximum Age for this Clinical Trial: 15 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Mental Health (NIMH)

Overall Clinical Trial Officials and Contacts

David J. Posey, MD, MS Principal Investigator Indiana University School of Medicine  

Overall Contact: Jennifer Mullett, RN, CCRP 317-274-1981 mullettj@iupui.edu

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00498173

Study ID Number: R01 MH77600

ClinicalTrials.gov Identifier: NCT00498173

Health Authority: United States: Federal Government

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