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

NCT00498173 | Completed Phase 3 Results DMC

• 2 other identifiers: R01MH077600DDTR B2-NDA
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

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.

Conditions

Autism

Keywords

Autistic Disorder; Autism Spectrum Disorder

Outcome Measures

Primary Outcomes (1)

• ADHD Rating Scale (ADHDRS)-Home Version Total Score (Randomized Phase)

  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.

  8 weeks

Secondary Outcomes (14)

• ADHD Rating Scale (ADHDRS)-Home Version Inattention and Hyperactivity Scores (Randomized Phase)

  8 weeks

• Aberrant Behavior Checklist (ABC) (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

Study Arms (2)

Atomoxetine

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Atomoxetine DRUG

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.

Also known as: Strattera

Atomoxetine

Placebo DRUG

Placebo tablets dosages: 5 mg, 10 mg, 25 mg, 40 mg.

Placebo

Eligibility Criteria

• Age: 5 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

Christian Sarkine Autism Treatment Center at Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Lurie Center - MassGeneral Hospital

Lexington, Massachusetts, 02421, United States

Location

Related Publications (1)

• Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.

  PMID: 37811711 DERIVED

MeSH Terms

Conditions

Autistic Disorder; Autism Spectrum Disorder

Interventions

Atomoxetine Hydrochloride

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Christopher John McDougle, M.D.
• Organization: Lurie Center for Autism, Massachusetts General Hospital

cmcdougle@mgh.harvard.edu

7818601721

Study Officials

• Christopher J. McDougle, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Lurie Center for Autism

Model Details: At the end of the 8-week double-blind, placebo-controlled study, participants randomized to placebo who are not responders at the end of 8 weeks will be treated with atomoxetine for 8 weeks during an open-label trial. All participants who are rated "much improved" or "very much improved" on the CGI-I following treatment with atomoxetine (i.e., atomoxetine responders) during either the 8-week placebo-controlled trial or the 8-week open-label phase for placebo nonresponders will be eligible to enter the 10-month open-label extension phase of the study.

Study Record Dates

• First Submitted: July 6, 2007
• First Posted: July 9, 2007
• Study Start: July 1, 2007
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: November 14, 2025
• Results First Posted: August 14, 2017

Record last verified: 2025-10

Locations

US (2)