ClinicalTrials.gov record NCT06227780

Alpha Auditory Entrainment for Cognitive Enhancement and Sensory Hypersensitivity in Youth With Developmental Disorders

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Jul 27, 2026

FX ENTRAIN: Perturbation of Neurodynamics Underlying Sensory Hyperarousal and Statistical Learning in Youth With FXS

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
Healthy volunteersAcceptedPeople who do not have the condition being studied who are allowed to take part. Some studies include both people with the condition and healthy volunteers; others may enrol only healthy volunteers.
Age5 years old to 10 years old
SexAll
LocationUnited States
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This randomized, quadruple-masked crossover study compares real alpha auditory entrainment with a sham sound in children aged 5–10. It enrolls three groups: Fragile X syndrome, autism spectrum disorder without a known genetic mutation, and typically developing controls. The study measures brain activity with EEG and a statistical learning (word-learning) task to see short-term effects.

What it is studying. The study tests whether playing individualized sounds designed to drive alpha brain rhythms (alpha auditory entrainment) changes EEG signatures (alpha and gamma activity) tied to sensory hyperarousal and statistical learning. It also examines whether those neural changes relate to performance on a word-learning task and whether features seen in people map onto existing mouse EEG data.

What the researchers hope to learn. To characterize neurodynamic differences in alpha and gamma brain activity in Fragile X and autism. To link those neural patterns to statistical learning (word segmentation) and individual variability. To test whether individualized closed-loop alpha auditory entrainment can perturb and normalize neural signatures relevant to sensory sensitivity and learning.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

Fragile X Syndrome (FXS) is a complex neurodevelopmental disorder caused by a mutation on the X chromosome. Scientists have investigated FXS extensively in both humans and animals. Thus far, phenotypic rescue in animal models has not resulted in treatment breakthroughs in humans, though some important discoveries have been made. Research has shown that individuals with FXS process sounds differently than those in the typical population, and they also show baseline differences in brain activity, including high gamma activity, increased theta activity, and decreased alpha activity. The investigators' central hypothesis is that these alterations in brain activity (specifically alpha and gamma activity) impair the brain's ability to process new information, thereby impeding cognitive functioning and increasing sensory sensitivity. The investigators propose that auditory entrainment, a technique that involves playing special sounds through headphones, will normalize brain activity in individuals with FXS and lead to increased cognitive function and decreased sensory hypersensitivity.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Other
  • Alpha Auditory Entrainment
  • Sham

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • FXS Cohort: 1) Aged 5-10 years, inclusive; 2) Patient has full FMR1 mutation confirmed by genetic testing.
  • ASD Cohort: 1) Aged 5-10 years, inclusive; 2) Have no known genetic mutation; 3) Have documentation of ASD diagnosis; 4) Score ≤ 15 on SCQ screen; 5) Be in good health per investigator.
  • TDC Cohort: 1) Aged 5-10 years, inclusive; 2) Have no known genetic mutation; 3) Have documentation of ASD diagnosis; 4) Score ≤ 15 on SCQ screen; 5) Be in good health per investigator; 6) Patient has met normal developmental milestones; Patient has no family history of heritable neuropsychiatric disorders; 7) Patient has an IQ greater than 85 on the Stanford-Binet; 8) Score ≤8 on an SCQ screen.

Exclusion criteria

  • All subjects: 1) Patient has auditory or visual impairments that cannot be corrected; 2) History of substance abuse or dependence within the past 6 months

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

Fragile X Syndrome (FXS) is an exemplar monogenetic neurodevelopmental disorder (NDD) where a tremendous body of multi-species translational research has elucidated the underlying molecular pathophysiology, and more recently, in-depth electrophysiology of cortical function. Thus far, phenotypic rescue in animal models has not resulted in treatment breakthroughs in humans. Central to this discrepancy is a poor understanding of the constituent neurodynamics of averaged group effects and individual variability in human brain activity as related to higher-level cognitive symptomatology and clinical phenotype. The investigators' large collection of preliminary data demonstrates that individuals with FXS do not mount precise neural responses to the sensory auditory chirp and, instead, have "noisy" asynchronous gamma activity. Furthermore, a marked reduction in alpha power suggests altered thalamocortical function, reducing the ability to detect signal from noise and representing potential tractable targets for "bottom-up" entrainment. This approach involves three scientific aims, which, if addressed, would ascertain underlying mechanisms that may alleviate sensory and cognitive impairments. First, the investigators will study transient, non-continuous features (neurodynamics) of alpha and gamma oscillations in resting-state EEG and sensory auditory chirp that model patient-level heterogeneity and constitute group effects (Aim 1A), and will also identify what, if any, of these novel features are conserved in the Fmr1-/-KO using preexisting murine EEG data and represent patient subgroups (Aim 1B). Second, the research team will extend into cognition by studying neurodynamics and circuit modeling associated with statistical learning (SL), which shares similar neural mechanisms to the sensory auditory chirp (Aim 2). Third, the investigators will use individualized closed-loop alpha auditory entrainment (AAE) to attempt the normalization of neural signatures of the sensory auditory chirp and SL tasks (Aim 3). Aim 1 and 2 findings will provide critical data to optimize closed-loop parameters of AAE to serve as a "bottom- up" neural probe to understand the mechanics of disorder-relevant circuit activity through perturbation of thalamocortical drive. Ascertaining the mechanisms underlying these alterations would have a high clinical impact, especially to enhance early intervention to alter the trajectory of intellectual development in which no definitive treatments are available.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participants are randomly assigned in a crossover so they receive both the active alpha auditory entrainment sound and a sham (carrier tone) in different sessions while wearing headphones/speakers. The study records brain activity with EEG during resting-state and auditory/statistical‑learning tasks and measures a Word Learning Index from those recordings. Sessions involve listening to sounds and completing passive learning/cognitive tasks; the study is described as quadruple-masked. The registry does not list invasive procedures (for example, no lumbar puncture or biopsies are mentioned).

How the study is structured. Participants are randomly assigned to the order of two sessions (real entrainment and sham) in a crossover design so each child experiences both conditions. The study is masked at four levels (quadruple) and uses EEG during resting and task-based recordings, including a statistical learning task; the main neural/behavioral effect is evaluated over a short timeframe (primary outcome at about 1 week).

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on fragile X syndrome

Clinical trials20 trials listed for fragile X syndromeEvery trial the registry lists for fragile X syndrome, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in fragile X syndrome researchLatest monthly update: September 2026. Includes: Multiple behavior challenges. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
May 24, 2023
Primary completion
May 24, 2027 (estimated)
Study completion
May 24, 2028 (estimated)
Target enrollment
180 participants (estimated)
Last updated on registry
Mar 30, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
Children's Hospital Medical Center, Cincinnati
Principal investigator
Ernest Pedapati, MD, Assistant Professor
Children's Hospital Medical Center, Cincinnati
Collaborators
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (1)

  • Cincinnati Children's Hospital Medical CenterRecruiting

    Cincinnati, Ohio, 45226 · United States

Terms used on this page · explanations by MedicalUpdates.ai

baseline
Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
Cohort
A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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