IMPACT-Ready Study

November 6, 2026 updated by: Coalition for Aligning Science

Aligning Research to Impact Autism (ARIA) Innovative Medicine and Precision Approaches to Clinical Trials (IMPACT)-Ready Study

The IMPACT-Ready Study is a multi-site, international short-term prospective natural history study to develop new outcome measures, clinical endpoints, and biomarkers for autism and related neurodevelopmental conditions. The primary objective is to systematically document over time the behavioral, medical, neurophysiological, and genetic presentation of children with profound autism and related neurodevelopmental conditions. Participants will be initially separated into two cohorts: those with a confirmed diagnosis of a monogenic disorder associated with profound autism, including ARID1B, GRIN2B, RNU4-2, SCN2A, SLC6A1, or other genes of interest (Cohort 1), or those with likely profound or profound autism without a definitive genetic cause for their autism at the time of enrollment who use few or no words to communicate, with significant cognitive impairments (Cohort 2).

All participants will complete a baseline visit, and a subset of participants will complete either 6-month or annual follow-up visits based on the results of their genetic testing and their age.

After whole genome sequencing and Fragile X testing at the baseline visit, Cohort 2 will be split into 2 groups: Cohort 2a (those with a definitive genetic cause for autism not identified) and Cohort 2b (those with the presence of pathogenic or likely pathogenic variant(s) in a neurodevelopmental gene other than one of the targeted genes of interest AND those that do not meet the criteria for profound/likely profound autism following baseline assessment).

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

The ARIA IMPACT-Ready Study aims to better understand and measure how autism and related neurodevelopmental conditions develop and change over time. What we learn may help improve future research and treatments. Eligibility criteria is children ages 0-18 years who have a pathogenic or likely pathogenic variant in ARID1B, GRIN2B, RNU4-2, SCN2A, SLC6A1, or other genes of interest AND children ages 2-18 years who have likely profound or profound autism with no known genetic cause and use few or no words to communicate (are minimally verbal or non-verbal), with significant cognitive impairments. Participation lasts up to 2 years, and depending on the child's age, it involves 1 to 5 study visits. Each visit will last between 5-8 hours and may be split over 2 to 3 days, if needed. During the study, participants will:

  • Provide a blood or cheek swab sample for whole genome sequencing (WGS). The blood or cheek sample is also required from biological parents, if available.
  • Complete physical and neurological exams
  • Participate in play-based activities and surveys to better understand cognitive (IQ), behavioral, and developmental skills.
  • Participate in studies to examine biomarkers of brain function, such as electroencephalography and eye tracking
  • Wear a smartwatch, an EEG headband, and have a thin mat placed under their mattress to monitor their sleep at home for 3 nights.
  • Parents will also be asked questions about their child's family and medical history.

Families receive a detailed behavioral report, genetic testing results and $250 for each completed visit. Reasonable travel costs will be covered.

Study Type

Observational

Enrollment (Estimated)

1250

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
    • Ontario
      • East York, Ontario, Canada
        • Holland Bloorview Rehabilitation Hospital/Hospital for Sick Children
        • Principal Investigator:
          • Evdokia Anagnostou, MD, FRCPC
        • Sub-Investigator:
          • Stephen Scherer, PhD, DSc, FRSC
        • Sub-Investigator:
          • Danielle Baribeau, MD, PhD
  • United Kingdom
      • Oxford, United Kingdom
        • University of Oxford/King's College London
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles/University of California Los Angeles
        • Principal Investigator:
          • Jonathan Santoro, MD
        • Sub-Investigator:
          • Rajsekar Rajaraman, MD, MS
        • Sub-Investigator:
          • Rujuta Wilson, MD
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Anschutz Medical Campus/Children's Hospital of Colorado
        • Principal Investigator:
          • Timothy Benke, MD, PhD
        • Sub-Investigator:
          • Scott Demarest, MD
        • Sub-Investigator:
          • Nicole Tartaglia, MD
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University/Georgia State University/Children's Healthcare of Atlanta
        • Principal Investigator:
          • Ami Klin, PhD
        • Sub-Investigator:
          • Warren Jones, PhD
        • Sub-Investigator:
          • Nathan Call, PhD, BCBA-D
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
        • Principal Investigator:
          • Siddharth Srivastava, MD
        • Sub-Investigator:
          • Susan Faja, PhD
        • Sub-Investigator:
          • Matthew Siegel, MD
    • New York
      • New York, New York, United States, 10032
        • New York State Psychiatric Institute/Weill Cornell Medicine/Columbia University Medical Center
        • Principal Investigator:
          • Jeremy Veenstra-Vanderweele, MD
        • Sub-Investigator:
          • William Fifer, PhD
        • Sub-Investigator:
          • Zachary Grinspan, MD, MS
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina at Chapel Hill
        • Principal Investigator:
          • Mark Shen, PhD
        • Sub-Investigator:
          • Jessica Girault, PhD
        • Sub-Investigator:
          • Gabriel Dichter, PhD
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
        • Principal Investigator:
          • Craig Erickson, MD
        • Sub-Investigator:
          • Ernest Pedapati, MD, MS, FAAP
        • Sub-Investigator:
          • Rebecca Schaffer, PsyD, HSPP
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia/University of Pennsylvania
        • Principal Investigator:
          • Eric Marsh, MD, PhD
        • Sub-Investigator:
          • Robert Schultz, PhD
        • Sub-Investigator:
          • Amanda Bennett, MD, MPH
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine/Texas Children's Hospital
        • Sub-Investigator:
          • Holly Harris, MD
        • Principal Investigator:
          • Jimmy Holder, MD, PhD
        • Sub-Investigator:
          • Mirjana Maletic-Savatic, MD, PhD
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital/University of Washington
        • Principal Investigator:
          • Sara Webb, PhD
        • Sub-Investigator:
          • Frederick Shic, PhD
        • Sub-Investigator:
          • Emily Neuhaus, PhD

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

1 second to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Children and young adults with autism and related neurodevelopmental conditions

Description

Inclusion Criteria

  • For Cohort 1: age 0-18 years with clinical documentation of a genetically-defined disorder associated with profound autism, including a pathogenic/likely pathogenic variant in ARID1B, GRIN2B, RNU4-2, SCN2A, or SLC6A1.
  • For Cohort 2: ages 2-18 years with profound autism or likely profound autism, either without previous genetic testing or previous testing that was non-diagnostic.

Exclusion Criteria

  • For Cohort 1: Aged over 18 years at enrollment.
  • For Cohort 2: Age <2 or >18 years at enrollment
  • For Cohort 2: Participants with an established genetic diagnosis for their autism on the basis of a pathogenic variant (or variants) identified in a non-target neurodevelopmental gene.
  • Primary language other than English or Spanish.
  • Treatment with an investigational drug, biological agent, or device as part of another research study, within 30 days prior to study enrollment.
  • Previous treatments involving disease-modifying therapies, such as gene therapy, antisense oligonucleotide (ASO), or a repurposed drug.

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

  • Observational Models: COHORT
  • Time Perspectives: PROSPECTIVE

Cohorts and Interventions

Group / Cohort
Cohort 1

Children and young adults (birth to 18 years) with confirmed pathogenic or likely pathogenic variants in genes strongly linked to autism, including ARID1B, GRIN2B, RNU4-2, SCN2A, SLC6A1, or other genes of interest. A formal diagnosis of profound autism is not required to participate. This group will be followed over time.
Cohort 2a

Children and young adults (2-18 years) with likely profound or profound autism without a definitive genetic cause for autism identified from whole-genome sequencing or Fragile X testing at the baseline visit. This cohort will be followed over time.
Cohort 2b

Children and young adults (2-18 years) with either 1) likely profound or profound autism with the presence of a genetic variant(s) in a gene other than one of the targeted genes of interest or another gene known to cause autism or 2) do not meet the study definition for profound/likely profound autism following baseline assessment. Meaningful genetic, clinical, and biomarker data will be collected from these participants at the baseline visit, but this cohort will not be followed over time.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cognition
Time Frame: 0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.

Cognition will be assessed using the Bayley Scales of Infant & Toddler Development-4 or the Stanford-Binet Intelligence Scales-5. The primary composite variable (40-160) will be evaluated, with higher scores indicating more advanced cognitive development.
0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.
Language & Communication
Time Frame: 0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.

Language and communication will be assessed using the Clinical Evaluation of Language Fundamentals-5 (CELF-5) or Preschool Language Scales-5 (PLS-5). The primary composite variable (0-130 for the CELF-5, 50-150 for the PLS-5) will be evaluated, with higher scores indicating more advanced language and communication.
0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.
Autism Symptoms
Time Frame: 0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.

Autism symptoms will be assessed using the Autism Diagnostic Observation Scales-2 (ADOS) or the Autism Observation Scale for Infants (AOSI). The primary composite variable (1-10 for the ADOS, 0-16 for the AOSI) will be evaluated, with lower scores indicating greater symptom severity.
0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.
Adaptive Behavior
Time Frame: 0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.

Adaptive behavior will be assessed using the Vineland Adaptive Behavior Scale-3. The primary composite variable (20-140) will be evaluated, with higher scores indicating better adaptive functioning.
0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.
Motor Skills
Time Frame: 0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.

Motor skills will be assessed using the Motor Assessment Battery for Children-3 (MABC-3) or the Peabody Developmental Motor Scales-3 (PDMS-3). The primary composite variable (0-100 for MABC-3, 50-150 for the PDMS-3) will be evaluated, with higher scores indicating more advanced motor skills.
0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genetic
Time Frame: At baseline visit

Whole genome sequencing and Fragile X testing (when applicable)
At baseline visit

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biomarkers & Quantitative Phenotyping
Time Frame: 0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.

High-density research EEG
0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.
Biomarkers & Quantitative Phenotyping
Time Frame: 0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.

Eye-tracking
0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.
Biomarkers & Quantitative Phenotyping
Time Frame: 0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.

Quantitative video motion capture
0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.
Biomarkers & Quantitative Phenotyping
Time Frame: 0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.

Overnight sleep monitoring
0-2 years old: 6-month assessment at baseline, and 6, 12, 18, and 24 month follow-up visits. Participants who reach 24 months during the study move to annual assessments. 2-18 years old: annual assessment at baseline, year 1 and year 2 follow-up visits.

Collaborators and Investigators

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

Sponsor

Coalition for Aligning Science

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 (Estimated)

November 1, 2026

Primary Completion (Estimated)

November 1, 2033

Study Completion (Estimated)

November 1, 2040

Study Registration Dates

First Submitted

September 3, 2026

First Submitted That Met QC Criteria

November 6, 2026

First Posted (Actual)

November 12, 2026

Study Record Updates

Last Update Posted (Actual)

November 12, 2026

Last Update Submitted That Met QC Criteria

November 6, 2026

Last Verified

November 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IMPACT-Ready-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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