Speech Discrimination for Fragile X Syndrome

Overseen By Craig Erickson, MD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Children's Hospital Medical Center, Cincinnati

Disqualifiers: Seizures, Premature birth, others

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

Compensation: Varies

Number of Visits: 7

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how children with Fragile X Syndrome perceive speech and sounds, as they often face challenges with language and sound sensitivity. Researchers will use tests and brain imaging to observe how these children process speech differently. Participants will listen to speech sounds to measure changes in brain activity. The study involves speech discrimination, also known as speech therapy or auditory training, to help assess these differences. Children who might be a good fit have Fragile X Syndrome, typical development, or a history of premature birth, can sit independently, and live in homes where English is spoken. As an unphased study, this trial offers a unique opportunity to contribute to understanding speech perception in children with Fragile X Syndrome.

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 this protocol is safe for children with Fragile X Syndrome?

Research shows that speech discrimination therapy, used in this study for Fragile X Syndrome, lacks specific safety data. However, studies have not reported major side effects, suggesting the therapy is generally well-tolerated. Speech discrimination involves listening to speech sounds while researchers monitor changes in brain activity. As this is neither a medication nor an invasive procedure, it is considered low risk. Participants typically do not experience negative effects from these non-invasive methods. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial for speech discrimination in Fragile X Syndrome because it explores a unique approach that could enhance our understanding of how individuals with this condition process speech sounds. Unlike traditional treatments that focus on behavioral therapies or medications to manage symptoms, this study investigates the brain's electrical and blood flow responses when listening to speech. By identifying specific changes in the brain's activity, this method could pave the way for developing new interventions that directly target communication challenges in Fragile X Syndrome, potentially leading to more effective and tailored therapies.

What evidence suggests that speech discrimination might be an effective treatment for Fragile X Syndrome?

Research shows that training to improve hearing and understanding of speech might help with speech and language issues in people with Fragile X Syndrome. In similar conditions, computer-based listening exercises significantly improved average scores for recognizing vowel sounds, from 63.1% to 84.8%. This trial will focus on participants listening to speech sounds while investigators measure electrical and hemodynamic changes in the brain. Although direct evidence for Fragile X Syndrome is limited, studying brain activity during speech tasks might lead to better treatments. While full proof for Fragile X is not yet available, early results in related areas are encouraging. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for infants with Fragile X Syndrome, a genetic condition that affects language and sound perception. It aims to understand how these children differ in speech understanding and hearing from an early age.

Inclusion Criteria

English is spoken at home

I have been diagnosed with Fragile X Syndrome, or I was born prematurely.

I can sit up on my own without help.

Exclusion Criteria

Not born prior to 32 weeks gestation (for typical development group and Fragile X group)

I haven't had a seizure in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Initial assessment of speech and language abilities, neuroimaging, and hearing tests

1-2 weeks

1 visit (in-person)

Longitudinal Assessment

Participants undergo EEG/fNIRS and other assessments at multiple age points to track development

18 months

Visits at 6, 12, 18, and 24 months

Follow-up

Participants are monitored for changes in auditory and language development

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Speech discrimination

Trial Overview

The study tests how babies with Fragile X Syndrome discriminate between different sounds. It involves behavioral assessments, brain imaging (fNIRS/EEG), and hearing tests to track the development of their speech and auditory processing.

How Is the Trial Designed?

Group I: Speech Sounds Experimental Treatment 1 Intervention

Participants listen to speech sounds while the investigators measure electrical and hemodynamic changes in the brain.

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Published Research Related to This Trial

In a study of 62 males with Fragile X syndrome, those with a mosaic pattern of premutation and full mutation alleles exhibited lower levels of irritability and inappropriate speech compared to those with only full mutation alleles and complete loss of FMR1 mRNA.

Higher levels of FMR1 mRNA were linked to increased irritability and lower quality of life scores, particularly in males with incomplete silencing of the FMR1 gene, suggesting that FMR1 mRNA levels could be an important factor in understanding behavioral outcomes in Fragile X syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FMR1 mRNA from full mutation alleles is associated with ABC-CFX scores in males with fragile X syndrome. Baker, EK., Arpone, M., Kraan, C., et al.[2021]

Boys with fragile X syndrome (FXS), whether they also have autism spectrum disorder (ASD) or not, showed similar phonological accuracy to typically developing (TD) boys but produced fewer intelligible words, indicating challenges in speech clarity.

Boys with Down syndrome (DS) had greater delays in phonological accuracy and intelligibility compared to both FXS and TD boys, highlighting more significant speech development issues in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phonological accuracy and intelligibility in connected speech of boys with fragile X syndrome or Down syndrome. Barnes, E., Roberts, J., Long, SH., et al.[2021]

This study reveals that Fmr1 knockout rats, a model for fragile X syndrome, show significant impairments in the cortical representation of speech sounds, despite being able to discriminate speech normally, indicating a disconnect between perception and processing.

The greatest deficits were found in the ventral auditory field, which is linked to emotional regulation, suggesting that these processing issues may contribute to emotional challenges in individuals with fragile X syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Degraded speech sound processing in a rat model of fragile X syndrome. Engineer, CT., Centanni, TM., Im, KW., et al.[2021]

A study involving 23 young males with Fragile X syndrome (FXS) found that their auditory brainstem responses (ABRs) were within normal limits, indicating typical auditory function despite the syndrome's associated developmental delays.

When compared to typically developing males matched for both developmental and chronological age, males with FXS showed no significant differences in hearing sensitivity or auditory pathway integrity, suggesting that FXS does not inherently affect auditory brainstem function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auditory brainstem responses in young males with Fragile X syndrome. Roberts, J., Hennon, EA., Anderson, K., et al.[2007]

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]

In the FXLEARN trial, which involved 110 children with fragile X syndrome (FXS), the mGluR5 negative allosteric modulator AFQ056 did not show a significant improvement in language learning compared to placebo, despite both groups making progress.

The study highlights that the promising results seen in animal models for mGluR5 NAMs do not necessarily translate to benefits in human subjects with FXS, indicating a need for better strategies to connect preclinical findings to human treatments in genetic neurodevelopmental disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of AFQ056 on language learning in fragile X syndrome. Berry-Kravis, E., Abbeduto, L., Hagerman, R., et al.[2023]

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]

Infants and toddlers with fragile X syndrome (FXS) show early language skill deficits compared to typical developmental expectations, although their skills may align with their overall developmental level.

Caregivers of children with FXS tend to use fewer vocalizations than caregivers of typically developing children, indicating a potential gap in the language learning environment that requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Quantitative Evaluation of Early Life Language Development in Fragile X Syndrome. Reisinger, DL., Shaffer, RC., Pedapati, EV., et al.[2020]

Speech-language pathologists observed that young males with fragile X syndrome (FXS) often have unique communication difficulties, including a preference for visually based and experiential learning, which necessitates individualized and syndrome-specific interventions.

Interventions should address specific challenges such as limited attention spans, sensory sensitivities, and anxiety, focusing on tailored speech and language goals that enhance verbal communication, listening skills, and social interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Intervention Practices and Communication Intervention Strategies for Young Males With Fragile X Syndrome. Mirrett, PL., Roberts, JE., Price, J.[2019]

In a study comparing 12 adult males with Fragile X syndrome to matched groups with nonspecific mental retardation and autism, no significant differences in speech and language measures were found, except for higher rates of echolalia in the autistic group.

There was a nonsignificant trend indicating that individuals with Fragile X syndrome may have poorer performance on expressive language measures, suggesting a need for further research into the specific language characteristics associated with this syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of language characteristics of mentally retarded adults with fragile X syndrome and those with nonspecific mental retardation and autism. Paul, R., Dykens, E., Leckman, JF., et al.[2019]

Citations

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withpower.com/trial/phase-fragile-x-syndrome-9-2022-9d06a

Speech Discrimination Assessments for Fragile X Syndrome

This study uses behavioral assessment of speech and language abilities, neuroimaging, and hearing tests to understand how speech and hearing are different in ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4034469/

Degraded speech sound processing in a rat model of fragile X ...

Neural classifier accuracy did not improve following speech training and still exhibited a 6% deficit in AAF, 7% deficit in A1, and 9% deficit in VAF compared ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT06088589?cond=speech%20perception%20in%20noise%20children%20&rank=4

Speech-in-noise Perception in Autism and Fragile X

The goal of this study is to identify which brain regions are active during speech-in-noise perception, as well as how those regions interact.

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pubs.asha.org

pubs.asha.org/doi/10.1044/2023_AJA-23-00078

Effectiveness of Computerized Auditory Training on ...

Mean scores of vowel recognition improved significantly from 63.1% to 84.8% after training, p = .006. Mean scores of consonant recognition ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S0891422224001719

Effects of a combined neuropsychological and cognitive ...

This study aimed to investigate the effectiveness of a combined neuropsychological and cognitive behavioral group therapy (nCBT) among young adults with FXS.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05957549

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Fragile X Syndrome (FXS) is the leading monogenic cause of intellectual disability and autism and is associated with extremely high risk for early delays in ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11144093/

State-of-the-art therapies for fragile X syndrome - PMC

The use of psychotropic medications should be combined with individualized therapies from psychology, speech and language therapy, occupational therapy, and ...

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fragilex.org/resources/treatment/assessment-fxs-clinicians/

Assessment of Fragile X Syndrome — For Clinicians

The FXS behavioral phenotype is characterized by problems with hyperactivity and impulsivity, inattentive behaviors, repetitive or stereotyped behavior and ...

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We will review the results of recent clinical trials conducted in FXS that were based on some of the preclinical findings, and discuss how the observed outcomes ...