AWARE: Management of ADHD in Autism Spectrum Disorder

NCT05916339 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: STUDY00003286
• Study Type: interventional
• Target: 500
• Locations: 2 countries
• Sites: 12

Brief Summary

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.

Conditions

ADHD; Autism Spectrum Disorder

Keywords

ADHD; Autism; ASD

Outcome Measures

Primary Outcomes (1)

• The Vanderbilt Parent Rating Scale

  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 Outcomes (2)

• Parent reported Clinical Global Impression

  16 Weeks

• Aberrant Behavior Checklist- Hyperactivity/Impulsivity subscale

  16 Weeks

Study Arms (2)

Stage 1 - Stimulant

ACTIVE COMPARATOR

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

Stage 2 - Alpha-2 Agonist or Alternate Stimulant

ACTIVE COMPARATOR

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.

Interventions

Randomization to either Amphetamine (AMP) class of stimulant medication or Methylphenidate (MPH) class of stimulant medication DRUG

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)

Stage 1 - Stimulant

Randomization to either Alpha 2 agonist class of medication or alternate class of stimulant. DRUG

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

Stage 2 - Alpha-2 Agonist or Alternate Stimulant

Eligibility Criteria

• Age: 4 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant and/or legal caregiver must be willing and able to give informed consent/assent for participation in this study.
• Participant and/or legal caregiver must be willing and able (in the Investigator's opinion) to comply with all study requirements.
• Participant must be between 4 and 17 years of age (inclusive) at time of enrollment.
• 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.).
• Participant must have the ability to consistently take medication (via pill, liquid or mixed with food/liquid).
• Participant must have a confirmed diagnosis of ADHD (based upon DSM-5 criteria and supportive evidence).
• Participant must have a consistent reporter (e.g., parent) who spends regular time with the child.
• 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.
• 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.
• Caregiver must be sufficiently fluent in English or Spanish to be able to complete questionnaires relevant to this study.

You may not qualify if:

• Participant has taken ADHD medication within the past 7 days.
• Participant is not stable on other medications (\< 4 weeks).
• Any other risk factor that might prevent patient from safely taking the study medications.

Sponsors & Collaborators

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

Study Sites (12)

University of California, Irvine

Irvine, California, 92697, United States

RECRUITING

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Maine Medical Center

Portland, Maine, 04102, United States

RECRUITING

Massachusetts General Hospital Lurie Center for Autism

Boston, Massachusetts, 02421, United States

RECRUITING

University of Rochester

Rochester, New York, 14642, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19178, United States

RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, 15262, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

University of Alberta, Glenrose Rehabilitation Hospital

Edmonton, Canada

RECRUITING

Holland Bloorview Kids Rehabilitation Hospital

Toronto, Canada

RECRUITING

Related Publications (78)

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MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Autistic Disorder

Interventions

Adenosine Monophosphate; Methylphenidate; 5,10-dihydro-5-methylphenazine

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Child Development Disorders, Pervasive

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Daniel Coury, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

• Karen Kuhlthau, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amanda James, BS

CONTACT

(614) 722-4006; Amanda.James@nationwidechildrens.org

Samantha Sharpe

CONTACT

(614) 722-8509; Samantha.Sharpe@nationwidechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Behavioral Pediatrics Physician

Study Record Dates

• First Submitted: May 31, 2023
• First Posted: June 23, 2023
• Study Start: October 1, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: October 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (10)