ADHDPhase 4NCT05916339
AWARE: Management of ADHD in Autism Spectrum Disorder
A Phase 4 study testing Randomization to either Amphetamine (AMP) class of stimulant medication or Methylphenidate (MPH) class of stimulant medication and Randomization to either Alpha 2 agonist class of medication or alternate class of stimulant. in people with ADHD and Autism Spectrum Disorder, run by Daniel Coury at 13 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 17 years
- Conditions the study is for
- ADHD, Autism Spectrum Disorder
- What is being tested?
- Randomization to either Amphetamine (AMP) class of stimulant medication or Methylphenidate (MPH) class of stimulant medication and Randomization to either Alpha 2 agonist class of medication or alternate class of stimulant.
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 13 sitesin 2 countries
- Study dates
- 1 Oct 2023to 30 Dec 2027
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
- 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.
Trial locations and contacts
13 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
13 sites in 2 countries
United States11 sites, 11 recruiting
- Recruiting
Massachusetts General Hospital Lurie Center for Autism
Boston, Massachusetts, 02421
Alexander Cordova, acordova1@mgh.harvard.edu
Ann Neumeyer, MD
- Recruiting
University of Virginia
Charlottesville, Virginia, 22903
Susie Hoffman, SRH@uvahealth.org
Richard Stevenson, MD
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Courtney Herberger, Courtney.Herberger@cchmc.org
Julia Anixt, MD
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
Johnny Dudley, 614-355-7584, Johnny.Dudley@nationwidechildrens.org
Eric Butter, PhD
- Recruiting
Prisma Health Upstate
Greenville, South Carolina, 29601
Vice President of Research Compliance and Administration, 864-797-7882, LegalAffairsDept@prismahealth.org
Karen L Ratliff-Schaub, MD, 864-454-5115, karen.ratliff-schaub@prismahealth.org
- Recruiting
University of California, Irvine
Irvine, California, 92697
Aisa Green-Hurley, 657-579-4100, apgreen@hs.uci.edu
Peter Chung, MD
- Recruiting
Children's Hospital Los Angeles
Los Angeles, California, 90027
Grace Anaya, granaya@chla.usc.edu
Kathryn Smith, RN, MN, DrPH
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19178
Danielle Collins, collinsd2@chop.edu
Carlyn Glatts, MD
- Recruiting
University of Pittsburgh
Pittsburgh, Pennsylvania, 15262
Sarah McAuliffe-Bellin, 412-235-5447, mcausj@upmc.edu
Benjamin Handen
- Recruiting
Maine Medical Center
Portland, Maine, 04102
Nicki Goldfeder, 207-661-5999, nichole.goldfeder@mainehealth.org
Danielle Sipsock, MD
- Recruiting
University of Rochester
Rochester, New York, 14642
Emily Wagner, Emily_wagner@urmc.rochester.edu
Lynn Cole, DNP
Canada2 sites, 2 recruiting
- Recruiting
University of Alberta, Glenrose Rehabilitation Hospital
Edmonton
Shannon Mah, 780-735-8285, shannon.mah@ahs.ca
Lonnie Zwaigenbaum, MD
- Recruiting
Holland Bloorview Kids Rehabilitation Hospital
Toronto
Christina Tsetsos, 416-425-6220 ext. 3561, ctsetsos@hollandbloorview.ca
Danielle Baribeau, MD, PhD
About this study
Official title: 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.
Read the 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.
- Conditions
- ADHD, Autism Spectrum Disorder
- Being tested
- Randomization to either Amphetamine (AMP) class of stimulant medication or Methylphenidate (MPH) class of stimulant medication, Randomization to either Alpha 2 agonist class of medication or alternate class of stimulant.
- Keywords
- ADHD, Autism, ASD
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Randomization to either Amphetamine (AMP) class of stimulant medication or Methylphenidate (MPH) class of stimulant medicationDrug
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)
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). Receives: Drug: Randomization to either Alpha 2 agonist class of medication or alternate class of stimulant. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 16 Weeks
Secondary outcomes (2)
Parent reported Clinical Global Impression
Parent reported Clinical Global Impression - Improvement is a Likert scale ranging from 1 to 7. Higher scores indicate worse outcome.
Measured: 16 Weeks
Aberrant Behavior Checklist- Hyperactivity/Impulsivity subscale
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.
Measured: 16 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2023
- Study start1 Oct 2023
- Primary completion1 Jan 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (78)Papers the sponsor has linked to this study.
- Other trials for ADHDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Daniel Coury
- Sponsor type
- University, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute, University of California, Irvine, Holland Bloorview Kids Rehabilitation Hospital, University of Rochester, Nationwide Children's Hospital, Children's Hospital Medical Center, Cincinnati, University of Virginia, University of Alberta, Massachusetts General Hospital, MaineHealth, University of Michigan, University of Pittsburgh, Children's Hospital of Philadelphia, Children's Hospital Los Angeles, Prisma Health-Upstate
- Responsible party
- Sponsor-investigator, Daniel Coury, Nationwide Children's Hospital
- Investigators
- Daniel Coury, MD, Principal investigator, Nationwide Children's HospitalKaren Kuhlthau, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05916339
- Sponsor's protocol ID
- STUDY00003286
- Status last verified
- Oct 2026
- First submitted
- 31 May 2023
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will not be shared.
Publications
Soke GN, Maenner MJ, Christensen D, Kurzius-Spencer M, Schieve LA. Prevalence of Co-occurring Medical and Behavioral Conditions/Symptoms Among 4- and 8-Year-Old Children with Autism Spectrum Disorder in Selected Areas of the United States in 2010. J Autism Dev Disord. 2018 Aug;48(8):2663-2676. doi: 10.1007/s10803-018-3521-1.
PubMed 29524016Maenner MJ, Shaw KA, Baio J; EdS1; Washington A, Patrick M, DiRienzo M, Christensen DL, Wiggins LD, Pettygrove S, Andrews JG, Lopez M, Hudson A, Baroud T, Schwenk Y, White T, Rosenberg CR, Lee LC, Harrington RA, Huston M, Hewitt A; PhD-7; Esler A, Hall-Lande J, Poynter JN, Hallas-Muchow L, Constantino JN, Fitzgerald RT, Zahorodny W, Shenouda J, Daniels JL, Warren Z, Vehorn A, Salinas A, Durkin MS, Dietz PM. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2016. MMWR Surveill Summ. 2020 Mar 27;69(4):1-12. doi: 10.15585/mmwr.ss6904a1.
PubMed 32214087Loomes R, Hull L, Mandy WPL. What Is the Male-to-Female Ratio in Autism Spectrum Disorder? A Systematic Review and Meta-Analysis. J Am Acad Child Adolesc Psychiatry. 2017 Jun;56(6):466-474. doi: 10.1016/j.jaac.2017.03.013. Epub 2017 Apr 5.
PubMed 28545751Neumeyer AM, Anixt J, Chan J, Perrin JM, Murray D, Coury DL, Bennett A, Farmer J, Parker RA. Identifying Associations Among Co-Occurring Medical Conditions in Children With Autism Spectrum Disorders. Acad Pediatr. 2019 Apr;19(3):300-306. doi: 10.1016/j.acap.2018.06.014. Epub 2018 Jul 24.
PubMed 30053632Davignon MN, Qian Y, Massolo M, Croen LA. Psychiatric and Medical Conditions in Transition-Aged Individuals With ASD. Pediatrics. 2018 Apr;141(Suppl 4):S335-S345. doi: 10.1542/peds.2016-4300K.
PubMed 29610415Spencer D, Marshall J, Post B, Kulakodlu M, Newschaffer C, Dennen T, Azocar F, Jain A. Psychotropic medication use and polypharmacy in children with autism spectrum disorders. Pediatrics. 2013 Nov;132(5):833-40. doi: 10.1542/peds.2012-3774. Epub 2013 Oct 21.
PubMed 24144704Kuhlthau KA, McDonnell E, Coury DL, Payakachat N, Macklin E. Associations of quality of life with health-related characteristics among children with autism. Autism. 2018 Oct;22(7):804-813. doi: 10.1177/1362361317704420. Epub 2017 Jul 9.
PubMed 28691502Lai MC, Kassee C, Besney R, Bonato S, Hull L, Mandy W, Szatmari P, Ameis SH. Prevalence of co-occurring mental health diagnoses in the autism population: a systematic review and meta-analysis. Lancet Psychiatry. 2019 Oct;6(10):819-829. doi: 10.1016/S2215-0366(19)30289-5. Epub 2019 Aug 22.
PubMed 31447415Danielson ML, Bitsko RH, Ghandour RM, Holbrook JR, Kogan MD, Blumberg SJ. Prevalence of Parent-Reported ADHD Diagnosis and Associated Treatment Among U.S. Children and Adolescents, 2016. J Clin Child Adolesc Psychol. 2018 Mar-Apr;47(2):199-212. doi: 10.1080/15374416.2017.1417860. Epub 2018 Jan 24.
PubMed 29363986Pastor P, Reuben C, Duran C, Hawkins L. Association between diagnosed ADHD and selected characteristics among children aged 4-17 years: United States, 2011-2013. NCHS Data Brief. 2015 May;(201):201.
PubMed 25974000Wolraich ML, Hagan JF Jr, Allan C, Chan E, Davison D, Earls M, Evans SW, Flinn SK, Froehlich T, Frost J, Holbrook JR, Lehmann CU, Lessin HR, Okechukwu K, Pierce KL, Winner JD, Zurhellen W; SUBCOMMITTEE ON CHILDREN AND ADOLESCENTS WITH ATTENTION-DEFICIT/HYPERACTIVE DISORDER. Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. Pediatrics. 2019 Oct;144(4):e20192528. doi: 10.1542/peds.2019-2528.
PubMed 31570648Newcorn JH, Kratochvil CJ, Allen AJ, Casat CD, Ruff DD, Moore RJ, Michelson D; Atomoxetine/Methylphenidate Comparative Study Group. Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: acute comparison and differential response. Am J Psychiatry. 2008 Jun;165(6):721-30. doi: 10.1176/appi.ajp.2007.05091676. Epub 2008 Feb 15.
PubMed 18281409Attention deficit hyperactivity disorder: diagnosis and management. London: National Institute for Health and Care Excellence (NICE); 2019 Sep. Available from http://www.ncbi.nlm.nih.gov/books/NBK493361/
PubMed 29634174Bolea-Alamanac B, Nutt DJ, Adamou M, Asherson P, Bazire S, Coghill D, Heal D, Muller U, Nash J, Santosh P, Sayal K, Sonuga-Barke E, Young SJ; British Association for Psychopharmacology. Evidence-based guidelines for the pharmacological management of attention deficit hyperactivity disorder: update on recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2014 Mar;28(3):179-203. doi: 10.1177/0269881113519509. Epub 2014 Feb 12.
PubMed 24526134Kooij SJ, Bejerot S, Blackwell A, Caci H, Casas-Brugue M, Carpentier PJ, Edvinsson D, Fayyad J, Foeken K, Fitzgerald M, Gaillac V, Ginsberg Y, Henry C, Krause J, Lensing MB, Manor I, Niederhofer H, Nunes-Filipe C, Ohlmeier MD, Oswald P, Pallanti S, Pehlivanidis A, Ramos-Quiroga JA, Rastam M, Ryffel-Rawak D, Stes S, Asherson P. European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD. BMC Psychiatry. 2010 Sep 3;10:67. doi: 10.1186/1471-244X-10-67.
PubMed 20815868