Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Massachusetts General Hospital
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Christopher John McDougle, M.D., Massachusetts General Hospital
ClinicalTrials.gov Identifier:
First received: July 6, 2007
Last updated: May 28, 2015
Last verified: May 2015
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.

Condition Intervention Phase
Drug: Atomoxetine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Targeted Pharmacologic Interventions for Autism: A Double-Blind, Placebo-Controlled Trial of Atomoxetine in Children and Adolescents With Autism

Resource links provided by NLM:

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • ADHD symptoms [ Time Frame: Measured at Weeks 2 and 4 and 6 and 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Irritability and anxiety [ Time Frame: Measured at Weeks 2 and 4,and 6, and 8 ] [ Designated as safety issue: Yes ]
  • Core autistic symptoms [ Time Frame: Measured at Weeks 2 and 4, and 6 and 8 ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: Measured at Weeks 2 and 4 and 6 and 8 ] [ Designated as safety issue: No ]

Estimated Enrollment: 86
Study Start Date: July 2007
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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.
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.
Other Name: Strattera
Placebo Comparator: 2
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.
Drug: Placebo
Placebo tablets dosages: 5 mg, 10 mg, 25 mg, 40 mg.

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.


Ages Eligible for Study:   5 Years to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   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
  • 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
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00498173

Contact: Jennifer Mullett, RN, CCRP 781-860-1711 LurieCenterResearch@partners.org

United States, Indiana
Christian Sarkine Autism Treatment Center at Riley Hospital for Children Completed
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Lurie Center - MassGeneral Hospital Recruiting
Lexington, Massachusetts, United States, 02421
Contact: Jennifer Mullett, RN, CCRP    781-860-1711    LurieCenterResearch@partners.org   
Principal Investigator: Christopher J McDougle, MD         
Sponsors and Collaborators
Massachusetts General Hospital
National Institute of Mental Health (NIMH)
Principal Investigator: Christopher J. McDougle, MD Massachusetts General Hospital
  More Information

Responsible Party: Christopher John McDougle, M.D., Director, Lurie Center for Autism, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00498173     History of Changes
Other Study ID Numbers: R01MH077600  DDTR B2-NDA 
Study First Received: July 6, 2007
Last Updated: May 28, 2015
Health Authority: United States: Federal Government

Keywords provided by Massachusetts General Hospital:
Autistic Disorder
Autism Spectrum Disorder

Additional relevant MeSH terms:
Autistic Disorder
Child Development Disorders, Pervasive
Mental Disorders
Neurodevelopmental Disorders
Atomoxetine Hydrochloride
Adrenergic Agents
Adrenergic Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 22, 2016