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

NCT06227780 | Recruiting DMC

• 2 other identifiers: 2022-09111R01HD108222-01
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Fragile X Syndrome; Autism Spectrum Disorder; Autistic Disorder; Asperger Syndrome

Keywords

Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Fragile X Syndrome; Fragile X; FXS; ASD; Asperger; Autism

Outcome Measures

Primary Outcomes (1)

• Alpha auditory entrainment versus sham effect on Word Learning Index during the Statistical Learning Passive Task.

  The Statistical Learning Passive Task uses an EEG-based measure of neural entrainment that uses inter-trial coherence (ITC) to calculate Word Learning Index (WLI). Patterns of EEG phase-locking, corresponding to a shift in processing from raw syllable units to cohesive words, reflect gradual statistical learning in the brain. The WLI effect can be quantified by creating a ratio of the inter-trail coherence for words versus syllables, as follows: WLI = Inter-trial Coherence word rate / Inter-trial Coherence syllable rate A higher WLI indicates a relatively stronger response to tri-syllabic nonwords compared to raw syllables, reflecting stronger word segmentation due to statistical learning.

  1 week

Other Outcomes (1)

• Alpha auditory entrainment versus sham effect on the Behavior Learning Effect during the Statistical Learning Active Task.

  1 week

Study Arms (3)

Fragile X Syndrome

EXPERIMENTAL

Fragile X Syndrome with full FMR1 mutations (\>200 CGG repeats; at least partial FMR1 gene methylation)

Other: Alpha Auditory Entrainment; Other: Sham

Autism Spectrum Disorder Controls

ACTIVE COMPARATOR

Age and sex-matched with FXS cohort

Other: Alpha Auditory Entrainment; Other: Sham

Typically Developing Controls

ACTIVE COMPARATOR

Subjects with neither disorder who have met normal developmental milestones

Other: Alpha Auditory Entrainment; Other: Sham

Interventions

Alpha Auditory Entrainment OTHER

Alpha Brainwave Entrainment (AAE) stimulus: starts at high theta range (7-Hz) through high alpha (13-Hz) in 2 Hz steps on a 500 Hz sine carrier tone Target frequency: 10 Hz Delivery: headphones/speakers

Also known as: Alpha Brainwave Entrainment, Alpha Binaural Beats, Pulsed Sound Stimulation, Sonic Entrainment

Autism Spectrum Disorder Controls; Fragile X Syndrome; Typically Developing Controls

Sham OTHER

Sham stimulus: carrier tone alone Target frequency: N/A Delivery: headphones/speakers

Autism Spectrum Disorder Controls; Fragile X Syndrome; Typically Developing Controls

Eligibility Criteria

• Age: 5 Years - 10 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45226, United States

RECRUITING

MeSH Terms

Conditions

Fragile X Syndrome; Autism Spectrum Disorder; Autistic Disorder; Asperger Syndrome; Neurodevelopmental Disorders

Interventions

salicylhydroxamic acid

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System; Child Development Disorders, Pervasive; Mental Disorders

Study Officials

• Ernest V Pedapati, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jae Citarella

CONTACT

513-636-0875; Jae.Citarella@cchmc.org

Grace Westerkamp

CONTACT

513-636-2332; grace.westerkamp@cchmc.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: As the randomization and "dispensing" of the intervention is conducted via software, investigators, study staff, and study subjects will all be blinded to the randomized study treatment assignments.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: All visits across all arms will follow identical procedures. Aim 1 and Aim 2 consist of a case-control study that will be completed over two visits, in which baseline data will be collected from participants that will be used to optimize the intervention delivered in Aim 3. Aim 3 consists of a two-visit, randomized controlled, crossover acute perturbation study to study the effect of alpha auditory entrainment (AAE) or sham stimulation on brain activity. AAE will be performed in two visits as a double-blind, sham-controlled crossover study such that each participant will receive AAE and sham in random order.

Study Record Dates

• First Submitted: November 16, 2023
• First Posted: January 29, 2024
• Study Start: May 24, 2023
• Primary Completion (Estimated): May 24, 2027
• Study Completion (Estimated): May 24, 2028
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: upon publication of results
• Access Criteria: Research data gathered as part of this study may be shared and provided to other investigators affiliated with the Neurobehavioral and Neurology Research Teams at CCHMC for the purpose of data sharing. If participants are enrolled in multiple studies, their research data will be shared across studies to reduce participant burden and avoid duplication of procedures. Only investigators/research team affiliated with CCHMC will have access to secured files and/or research data and will be well-informed regarding the protection of participants' rights to confidentiality.

Locations

US (1)