Targeted Pharmacologic Interventions for Autism: A Double-Blind, Placebo-Controlled Trial of Atomoxetine in Children and Adolescents With Autism
Overview
- Phase
- Phase 3
- Intervention
- Atomoxetine
- Conditions
- Autism
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 60
- Locations
- 2
- Primary Endpoint
- ADHD Rating Scale (ADHDRS)-Home Version Total Score (Randomized Phase)
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Christopher John McDougle, M.D.
Director, Lurie Center for Autism
Massachusetts General Hospital
Eligibility Criteria
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
- •Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (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 inhibitors\[MAO\])
- •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
Arms & Interventions
Atomoxetine
Participants will receive flexibly dosed atomoxetine for 8 weeks. Dosage can be increased over the first 4 weeks of study participation and will then be held constant for the remainder of the 8-week trial.
Intervention: Atomoxetine
Placebo
Participants will receive blinded, matched placebo for 8 weeks. Dosage can be increased over the first 4 weeks of study participation and will then be held constant for the remainder of the 8-week trial.
Intervention: Placebo
Outcomes
Primary Outcomes
ADHD Rating Scale (ADHDRS)-Home Version Total Score (Randomized Phase)
Time Frame: 8 weeks
The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD-RS-IV is investigator-administered biweekly during the 8-week double-blind, placebo-controlled phase of the study. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. The total score can range form 0 to 54, with a higher score indicating greater severity. Estimates are adjusted for baseline score, study stratum, and site, which were set at their sample means.
Secondary Outcomes
- Change in ADHD Rating Scale (ADHDRS)-Home Version Total Score (Open-label Trial)(8 weeks)
- Change in ADHD Rating Scale (ADHDRS)-Home Version Inattention and Hyperactivity Scores (Open-label Trial)(8 weeks)
- Change in Pediatric Quality of Life Inventory (Open-label Trial)(8 weeks)
- Change in Pediatric Anxiety Rating Scale, 5-item Total (Open-label Trial)(8 weeks)
- ADHD Rating Scale (ADHDRS)-Home Version Inattention and Hyperactivity Scores (Randomized Phase)(8 weeks)
- Aberrant Behavior Checklist (ABC) (Randomized Phase)(8 weeks)
- Pediatric Anxiety Rating Scale, 5-Item Total (Randomized Phase)(8 weeks)
- Social Responsiveness Scale (SRS) (Randomized Phase)(8 weeks)
- Vineland Adaptive Behavior Scales (VABS) Composite Score (Randomized Phase)(8 weeks)
- Pediatric Quality of Life Inventory (Randomized Phase)(8 weeks)
- Odds of Clinical Global Impression-Improvement Scale, Very Much or Much Improved (1 or 2) (Randomized Phase)(8 weeks)
- Change in Aberrant Behavior Checklist (ABC) (Open-label Trial)(8 weeks)
- Change in Vineland Adaptive Behavior Scales (VABS) Composite Score (Open-label Trial)(8 weeks)
- Change in Social Responsiveness Scale (SRS) (Open-label Trial)(8 weeks)