Alpha Auditory Entrainment for Fragile X Syndrome

(ENTRAIN Trial)

Recruiting at 1 trial location

Overseen By Jae Citarella

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Children's Hospital Medical Center, Cincinnati

Disqualifiers: Auditory impairments, Visual impairments, Substance abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 week

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist individuals with Fragile X Syndrome (FXS) using special sounds played through headphones, known as Alpha Auditory Entrainment. Researchers believe this approach could enhance brain activity, facilitate information processing, and reduce sensitivity to sensory input in people with FXS. They are testing this method on individuals with FXS and comparing the results with two other groups: those with Autism Spectrum Disorder and typically developing individuals. Individuals with FXS confirmed through genetic testing may be suitable candidates for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new ways of managing FXS.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that auditory entrainment is safe for individuals with Fragile X Syndrome?

Research shows that Alpha Auditory Entrainment, which involves listening to specific sounds through headphones, is under study for its potential benefits for people with Fragile X Syndrome (FXS). Although this method is still in testing, some safety information is available.

Earlier studies did not report any major side effects from this technique. Researchers observed changes in brain activity, which might affect how people with FXS process information and respond to sensory input. These studies found no significant negative effects from the sounds used in the treatment.

As this trial is in its early stages, safety information remains limited. However, the absence of serious negative reactions in past studies offers some initial reassurance. It is important to note that more research is needed to fully understand the safety and effectiveness of this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Alpha Auditory Entrainment for Fragile X Syndrome because it uses sound frequencies to potentially improve brain function, offering a non-invasive alternative to traditional medications. Unlike current treatments, which primarily involve behavioral therapy and medications like antipsychotics or stimulants to manage symptoms, this technique aims to directly influence brainwave patterns. By targeting the brain's natural rhythms, Alpha Auditory Entrainment could provide a novel way to enhance cognitive and behavioral outcomes without the side effects often associated with pharmaceutical treatments.

What evidence suggests that Alpha Auditory Entrainment could be an effective treatment for Fragile X Syndrome?

Research has shown that people with Fragile X Syndrome (FXS) exhibit different brain activity, particularly in their alpha brain waves. This trial tests Alpha Auditory Entrainment, a technique targeting these often disrupted alpha waves. Participants listen to specific sounds through headphones, which may help balance brain activity. While human data remains limited, early animal studies and theoretical research suggest this method might enhance thinking skills and reduce sensory problems in individuals with FXS. This approach offers a novel way to address the unique brain activity associated with FXS. ^{1 2 3 4 6}

Who Is on the Research Team?

Ernest V Pedapati, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

This trial is for young individuals with developmental disorders such as Autism Spectrum Disorder, Asperger Syndrome, and Fragile X Syndrome. It's designed to help those who have cognitive challenges and are overly sensitive to sensory input.

Inclusion Criteria

TDC Cohort: Aged 5-15 years, inclusive; Have no known genetic mutation; Have documentation of ASD diagnosis; Score ≤ 15 on SCQ screen; Be in good health per investigator; Patient has met normal developmental milestones; Patient has no family history of heritable neuropsychiatric disorders; Patient has an IQ greater than 85 on the Stanford-Binet; Score ≤8 on an SCQ screen.

I am aged 5-15, have ASD without genetic mutations, scored ≤ 15 on SCQ, and am in good health.

I am between 5 and 15 years old with a confirmed full FMR1 mutation.

Exclusion Criteria

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo alpha auditory entrainment to normalize brain activity and improve cognitive function and sensory hypersensitivity

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Alpha Auditory Entrainment

Trial Overview The study tests Alpha Auditory Entrainment—a technique using special sounds played through headphones—to see if it can improve brain activity, cognition, and reduce sensory hypersensitivity in participants with these conditions.

How Is the Trial Designed?

Group I: Fragile X Syndrome Experimental Treatment 2 Interventions

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

Group II: Autism Spectrum Disorder Controls Active Control 2 Interventions

Age and sex-matched with FXS cohort

Group III: Typically Developing Controls Active Control 2 Interventions

Subjects with neither disorder who have met normal developmental milestones

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

In individuals with Fragile X syndrome (n = 65), there is a notable alteration in brain activity, characterized by a slower dominant alpha rhythm and a shift in alpha frequency towards the front of the brain, which may contribute to sensory processing issues.

These changes in alpha activity suggest that disruptions in thalamocortical physiology play a significant role in the heightened excitability of the neocortex observed in Fragile X syndrome, indicating a need for further exploration of these neural mechanisms beyond what has been studied in animal models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empirical Frequency Bound Derivation Reveals Prominent Mid-Frontal Alpha Associated with Neurosensory Dysfunction in Fragile X Syndrome. Pedapati, EV., Sweeney, JA., Schmitt, LM., et al.[2023]

Children with fragile X syndrome showed significantly larger N1 responses to standard auditory tones compared to age-matched controls, indicating heightened auditory processing sensitivity.

The study also found that fragile X children did not exhibit habituation of the N1 response or sensitization of the N2 response to repeated tones, suggesting abnormal auditory stimulus processing in their brains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmentation of auditory N1 in children with fragile X syndrome. Castrén, M., Pääkkönen, A., Tarkka, IM., et al.[2019]

In a study of 933 individuals with fragile X syndrome (FXS), sensory symptoms (SS) and signs of hyperarousal (HA) were more prevalent in males, with 87% of males experiencing SS compared to 68% of females, indicating a gender difference in symptom expression.

The presence of strong sensory responses was linked to more behavioral problems and limited participation in daily activities, highlighting the need for further research on how these symptoms affect individuals with FXS and their families.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensory Symptoms and Signs of Hyperarousal in Individuals with Fragile X Syndrome: Findings from the FORWARD Registry and Database Multisite Study. Lachiewicz, AM., Stackhouse, TM., Burgess, K., et al.[2023]

Individuals with fragile X syndrome (FXS) exhibit distinct auditory processing abnormalities, including larger N1 and P2 amplitudes and abnormal modulation of these responses, which may impact language development and pattern recognition.

Despite showing a normal developmental trajectory for most auditory measures, participants with FXS demonstrate age-independent and gender-dependent challenges in processing novel stimuli, suggesting potential biomarkers for clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Neural Response to Novel Sounds in Fragile X Syndrome: Potential Biomarkers. Ethridge, L., Thaliath, A., Kraff, J., et al.[2022]

The study found that adolescents and adults with fragile X syndrome (FXS) exhibited decreased gamma band phase-locking in their auditory cortex, indicating altered neural entrainment compared to healthy controls.

These neural abnormalities were linked to heightened sensory sensitivities and social communication deficits, suggesting that targeting the functionality of fast-spiking interneurons could be a potential therapeutic strategy for FXS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome. Ethridge, LE., White, SP., Mosconi, MW., et al.[2018]

In a study of 36 adolescents and adults with Fragile X syndrome (FXS) compared to 40 typically developing controls, individuals with FXS exhibited significant differences in alpha brain wave activity, particularly in the right hemisphere, which may affect sensory processing.

Males with FXS showed more frequent bursts of alpha activity, while females had fewer bursts but maintained high alpha states longer, suggesting different mechanisms of sensory processing and clinical presentation between sexes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemispheric Utilization of Alpha Oscillatory Dynamics as a Unique Biomarker of Neural Compensation in Females with Fragile X Syndrome. Norris, JE., DeStefano, LA., Schmitt, LM., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06227780

Study Details | NCT06227780 | Alpha Auditory Entrainment ... The investigators propose that auditory entrainment, a technique that involves playing special sounds through headphones, will normalize brain activity in ...

2. withpower.com withpower.com/trial/alpha-auditory-entrainment-for-fragile-x-syndrome-449c7

Alpha Auditory Entrainment for Fragile X Syndrome Alpha Auditory Entrainment is unique because it targets the brain's alpha waves, which are often disrupted in Fragile X Syndrome, to help manage symptoms like ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12454403/

FX ENTRAIN: scientific context, study design, and biomarker ... During resting-state EEG, individuals with FXS demonstrated a reduction and global leftward shift in alpha, while studies in Fmr1–/– KO mice ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11838689/

Auditory steady-state response deficits in Fragile X Syndrome ... The present study aims to evaluate the 40 Hz auditory steady state response (ASSR) in FXS to evaluate stimulus representation maintenance in FXS.

5. cincinnatichildrens.org cincinnatichildrens.org/service/c/clinical-trials/studies/entrain-study-121124

Clinical Trials / Research Studies ... Cincinnati Children's is conducting a study to see if listening to specific sounds can help improve learning and sensory symptoms in children with FXS.

6. nature.com nature.com/articles/s41598-020-75893-x

Gamma power abnormalities in a Fmr1-targeted transgenic ... Fmr1-KO rats exhibited reduced basal alpha power and enhanced gamma power, and these rats showed enhanced locomotor activity in novel environment.