AWARE: Management of ADHD in Autism Spectrum Disorder

October 27, 2025 updated by: Daniel Coury

Comparative Effectiveness of Pharmacologic Management of ADHD in Children and Youth With Autism Spectrum Disorder

This study is a pragmatic clinical trial examining the comparative effectiveness of two stimulant medications (methylphenidate and amphetamine) in the treatment of ADHD in children and adolescents with autism. Using a sequential, multiple assignment randomization trial (SMART) design the study will not only assess these two medications but also the role of an increasingly popular class of ADHD medication, the alpha-2 agonists. Findings from this study will help improve clinicians' approach to medication selection and reduce the repeated trials of multiple medications that are current standard care.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Current data shows that 1 in 54 children in the United States are diagnosed with autism spectrum disorder (ASD). Additional data shows that those diagnosed with autism are also at risk for being diagnosed with a co-occurring condition such as attention deficit/hyperactivity disorder (ADHD). Managing the symptoms of each can be challenging for providers, patients, and parents.

Patients with ASD who are diagnosed with ADHD often face the challenge of finding the best medication options to treat symptoms. It is known that children with ASD and ADHD frequently respond differently to these treatments than typically developing (TD) children. Currently, no clear recommendations exist for parents or providers to follow to guide best medication options for patients with ASD and ADHD. This lack of medication knowledge and suboptimal medication management can lead to poor results and have substantial negative life impact for patients and their families.

The main goal of this study is to determine if the most prescribed medications for ADHD in TD children are similarly effective for patients who also have a diagnosis of autism. The results of this study will improve provider understanding of first-line stimulant medicines, methylphenidate and amphetamine compound, with ASD patients. Parents will determine medication effectiveness through discussion with their child and with their doctor as well as their own observations and will drive the medication adjustment process. Parents will provide ratings of effectiveness using the Clinical Global Impression measure every two weeks and the Aberrant Behavior Checklist and the Vanderbilt Parent Rating Scale will be completed monthly. For those patients who do not respond to first-line medicines, this study will further develop the understanding of second-line medication options, the alpha2 agonists guanfacine and clonidine. Parents will provide ratings using the same measures as before. Additional study measures will collect and review parent/caregiver input in the process of determining medication continuation. Most measures will be completed through electronic portals, reducing the need for families to come to the hospital to participate in this study.

While these medications are routinely prescribed to treat ADHD in children and adolescents with ASD, their relative effectiveness is not known. Randomizing participants to these different medicines in this format, called a SMART (Sequential Multiple Assignment Randomization Trial) design, will provide data on how well these medications work in children with ASD and ADHD, how they work compared to each other, and how their side effects differ from use in TD children. This study will also examine the effect of these medicines on target problems identified by parents, such as oppositional behavior. Parents/caregivers will be a significant part of the data and input captured to determine if medication should continue or be discontinued. The care team of patient, parent, and provider is solid in this project and will lead to optimal decision pathways for future patients with autism.

The aims outlined in this study are beneficial to patients with autism and their families/caregivers who often help navigate health care with them for life. Having access to evidence-based best practices when making medication decisions can impact and expedite positive outcomes in managing the symptoms of ADHD. When symptoms are managed at optimal levels, patients can focus on building life skills and accessing opportunities toward meaningful life outcomes.

Coproduced with parents and providers, this study is designed to reduce the trial and error aspect of prescribing ADHD medications and build provider and parent knowledge in best practice. The patient and family voice are an integral part of the study design process. This coproduction of treatment evidence helps ensure best outcomes for the patient and is supported by the inclusion of stakeholders. Participants will be children 4 to 17 years of age recruited from The Autism Care Network, the first and only network of its kind focused on better autism care, delivered at scale and at speed, to improve health and quality of life for children with autism and their families throughout North America. Twelve of the 20 network sites will participate in this study, each with providers and patients' parents committed to ensuring more than 500 patients will be part of this study and who are also committed to continuously improving whole-person and whole-family autism care.

Study Type

Interventional

Enrollment (Estimated)

500

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
      • Edmonton, Canada
        • Recruiting
        • University of Alberta, Glenrose Rehabilitation Hospital
        • Contact:
        • Principal Investigator:
          • Lonnie Zwaigenbaum, MD
      • Toronto, Canada
        • Recruiting
        • Holland Bloorview Kids Rehabilitation Hospital
        • Principal Investigator:
          • Danielle Baribeau, MD, PhD
        • Contact:
  • United States
    • California
      • Irvine, California, United States, 92697
        • Recruiting
        • University of California, Irvine
        • Principal Investigator:
          • Peter Chung, MD
        • Contact:
      • Los Angeles, California, United States, 90027
        • Recruiting
        • Children's Hospital Los Angeles
        • Contact:
        • Principal Investigator:
          • Kathryn Smith, RN, MN, DrPH
    • Maine
      • Portland, Maine, United States, 04102
        • Recruiting
        • Maine Medical Center
        • Principal Investigator:
          • Danielle Sipsock, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02421
        • Recruiting
        • Massachusetts General Hospital Lurie Center for Autism
        • Principal Investigator:
          • Ann Neumeyer, MD
        • Contact:
    • New York
      • Rochester, New York, United States, 14642
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital Medical Center
        • Principal Investigator:
          • Julia Anixt, MD
        • Contact:
      • Columbus, Ohio, United States, 43205
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19178
        • Recruiting
        • Children's Hospital of Philadelphia
        • Principal Investigator:
          • Carlyn Glatts, MD
        • Contact:
      • Pittsburgh, Pennsylvania, United States, 15262
        • Recruiting
        • University of Pittsburgh
        • Principal Investigator:
          • Benjamin Handen
        • Contact:
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • University of Virginia
        • Principal Investigator:
          • Richard Stevenson, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Participant and/or legal caregiver must be willing and able to give informed consent/assent for participation in this study.
  2. Participant and/or legal caregiver must be willing and able (in the Investigator's opinion) to comply with all study requirements.
  3. Participant must be between 4 and 17 years of age (inclusive) at time of enrollment.
  4. Participant must have a confirmed diagnosis of ASD based on supportive evidence (e.g. referring physician's report, medical records, such as ADOS or CARS, etc.).
  5. Participant must have the ability to consistently take medication (via pill, liquid or mixed with food/liquid).
  6. Participant must have a confirmed diagnosis of ADHD (based upon DSM-5 criteria and supportive evidence).
  7. Participant must have a consistent reporter (e.g., parent) who spends regular time with the child.
  8. Participant can be on other psychotropic medications (selective serotonin reuptake inhibitor (SSRI), atypical antipsychotic, anticonvulsant) if dose has been stable for > 4 weeks prior to consent with no plans for a dose change during the study.
  9. It has been at least 7 days since the participant last took an ADHD medication and the presiding clinician believes this to be a sufficient amount of time.
  10. Caregiver must be sufficiently fluent in English or Spanish to be able to complete questionnaires relevant to this study.

Exclusion Criteria:

  1. Participant has taken ADHD medication within the past 7 days.
  2. Participant is not stable on other medications (< 4 weeks).

  3. Any other risk factor that might prevent patient from safely taking the study medications.

    • There are no inclusion/exclusion criteria based upon participant IQ. We will include individuals across the entire range of cognition, just as practitioners are asked to treat ADHD in children with ASD across the entire IQ range.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Stage 1 - Stimulant

This proposed naturalistic, pragmatic clinical trial does not involve investigational drugs. Sequential, multiple assignment randomized trial (SMART) pragmatic clinical trial.

Stage 1 - randomization to either Amphetamine (AMP) or Methylphenidate (MPH). The specific medication prescribed by the physician will be determined by discussion between physician and parent / caregiver and review of the subject's insurance coverage. Subjects will receive their medication from their pharmacy.
Drug: Randomization to either Amphetamine (AMP) class of stimulant medication or Methylphenidate (MPH) class of stimulant medication

Amphetamine (AMP) medication names: Adderall, Adderall XR, Adzenys ER, Adzenys XR-ODT, Dayanavel XR, Dexedrine (spansule), Dexedrine (tablet), Mydayis, Procentra liquid

Methylphenidate (MPH) medication names: Adhansia XR, Aptensio XR, Azstarys, Concerta, Cotempla XR-ODT, Daytrana, Focalin, Focalin XR, Jornay PM. Metadate CD, Methylin (liquid), Ritalin, Ritalin LA, Quillichew ER, Quillivant XR (liquid)
Active Comparator: Stage 2 - Alpha-2 Agonist or Alternate Stimulant

Stage 2 - randomization to either Alpha-2 Agonist or other stimulant not randomized to in Stage 1: Amphetamine (AMP) or Methylphenidate (MPH).

(frequency, dosage, format, and duration dependent on participant and study doctor discussion).
Drug: Randomization to either Alpha 2 agonist class of medication or alternate class of stimulant.

If first line stimulant therapy (Amphetamine/Methylphenidate) is deemed not effective or tolerable, re-randomization to the alternate stimulant or alpha-2 agonist will occur. If participant is satisfied with first line stimulant treatment, first-line stimulant therapy will continue.

Catapres, Clonidine, Guanfacine, Intuniv, Kapvay, Tenex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Vanderbilt Parent Rating Scale
Time Frame: 16 Weeks
The primary outcome measure is The Vanderbilt Parent Rating Scale for ADHD consists of 18 item, each scored from 0 to 3. It has a minimum score of 0, maximum score of 54. Higher scores indicate worse outcome.
16 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Parent reported Clinical Global Impression
Time Frame: 16 Weeks
Parent reported Clinical Global Impression - Improvement is a Likert scale ranging from 1 to 7. Higher scores indicate worse outcome.
16 Weeks
Aberrant Behavior Checklist- Hyperactivity/Impulsivity subscale
Time Frame: 16 Weeks
Aberrant Behavior Checklist- Hyperactivity/Impulsivity subscale consists of 16 items, each scored from 0 to 3. It has a minimum score of 0, maximum score of 48. Higher scores indicate worse outcome.
16 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Daniel Coury

Collaborators

Patient-Centered Outcomes Research Institute
Massachusetts General Hospital
Children's Hospital of Philadelphia
University of Pittsburgh
University of Michigan
University of Alberta
Nationwide Children's Hospital
University of California, Irvine
Children's Hospital Medical Center, Cincinnati
University of Virginia
University of Rochester
Children's Hospital Los Angeles
Holland Bloorview Kids Rehabilitation Hospital
MaineHealth

Investigators

  • Principal Investigator: Daniel Coury, MD, Nationwide Children's Hospital
  • Principal Investigator: Karen Kuhlthau, PhD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2023

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

December 30, 2027

Study Registration Dates

First Submitted

May 31, 2023

First Submitted That Met QC Criteria

June 14, 2023

First Posted (Actual)

June 23, 2023

Study Record Updates

Last Update Posted (Estimated)

October 29, 2025

Last Update Submitted That Met QC Criteria

October 27, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00003286

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD will not be shared.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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