Clincosm LogoSign in Get a demo

Management of ADHD in Autism Spectrum Disorder

Sponsor
Daniel Coury (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05916339
Collaborator
Patient-Centered Outcomes Research Institute (Other), University of California, Irvine (Other), Holland Bloorview Kids Rehabilitation Hospital (Other), Children's Hospital of Philadelphia (Other), University of Rochester Golisano Children's Hospital (Other), Nationwide Children's Hospital (Other), Children's Hospital Medical Center, Cincinnati (Other), University of Pittsburgh (Other), Children's Hospital Los Angeles (Other), University of Virginia (Other), University of Alberta (Other), Massachusetts General Hospital (Other), MaineHealth (Other), University of Michigan (Other)
500
Enrollment
12
Locations
2
Arms
51
Anticipated Duration (Months)
41.7
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Randomization to either Amphetamine (AMP) class of stimulant medication or Methylphenidate (MPH) class of stimulant medication
  • Drug: Randomization to either Alpha 2 agonist class of medication or alternate class of stimulant.
 Phase 4

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 Design

Study Type:
Interventional
Anticipated Enrollment :
500 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Health Services Research
Official Title:
Efficacy of Pharmacologic Management of ADHD in Children and Youth With Autism Spectrum Disorder
Anticipated Study Start Date :
Oct 1, 2023
Anticipated Primary Completion Date :
Mar 1, 2027
Anticipated Study Completion Date :
Dec 30, 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. The Vanderbilt Parent Rating Scale [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.

Secondary Outcome Measures

  1. Parent reported Clinical Global Impression [16 Weeks]

    Parent reported Clinical Global Impression - Improvement is a Likert scale ranging from 1 to 7. Higher scores indicate worse outcome.

  2. Aberrant Behavior Checklist- Hyperactivity/Impulsivity subscale [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
4 Years to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  1. Patient and/or legally authorized representative must be willing and able to give informed consent/assent for participation in this study.

  2. Patient and their caregiver must be willing and able (in the Investigator's opinion) to comply with all study requirements.

  3. Patient must be between 4 and 17 years of age (inclusive) at time of enrollment.

  4. Patient must have a confirmed diagnosis of ASD based on supportive evidence (e.g. referring physician's report, medical records, such as ADOS (Autism Diagnostic Observation Schedule) or CARS (Childhood Autism Rating Scale), etc.).

  5. Patient must have the ability to consistently take medication (via pill, liquid or mixed with food/liquid).

  6. Patient must have a confirmed diagnosis of ADHD (based upon DSM-5 criteria and supportive evidence).

  7. Patient must have a consistent reporter (e.g., parent) who spends regular time with the child.

  8. Patient 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.

  1. Patient with prior trial of ADHD medication more than one year before enrollment, based on clinician judgement of reason for prior trial failure.

  2. Patient and/or family/caregiver must be sufficiently fluent in English or Spanish to be able to complete questionnaires relevant to this study.

Exclusion Criteria:

  1. Patient history of more than one prior trial of an ADHD medication within the past year.

  2. Less than 4 weeks since last ADHD medication was taken.

  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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of California, Irvine Irvine California United States 92697
2 Children's Hospital Los Angeles Los Angeles California United States 90027
3 Maine Medical Center Portland Maine United States 04102
4 Massachusetts General Hospital Lurie Center for Autism Boston Massachusetts United States 02421
5 University of Rochester Rochester New York United States 14642
6 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
7 Nationwide Children's Hospital Columbus Ohio United States 43205
8 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19178
9 University of Pittsburgh Pittsburgh Pennsylvania United States 15262
10 University of Virginia Charlottesville Virginia United States 22903
11 University of Alberta, Glenrose Rehabilitation Hospital Edmonton Canada
12 Holland Bloorview Kids Rehabilitation Hospital Toronto Canada

Sponsors and Collaborators

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

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Daniel Coury, Behavioral Pediatrics Physician, Nationwide Children's Hospital
ClinicalTrials.gov Identifier:
NCT05916339
Other Study ID Numbers:
  • STUDY00003286
First Posted:
Jun 23, 2023
Last Update Posted:
Jun 23, 2023
Last Verified:
Jun 1, 2023
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Keywords provided by Daniel Coury, Behavioral Pediatrics Physician, Nationwide Children's Hospital
ADHD
Autism
ASD
Additional relevant MeSH terms:
Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Methylphenidate
Amphetamine
Central Nervous System Stimulants

Study Results

No Results Posted as of Jun 23, 2023