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

Trial Summary

What is the purpose of this trial?

Individuals with Fragile X Syndrome show differences in how they understand and learn language from infancy. They frequently have lifelong delays in speech and language as well. In addition, they experience other auditory symptoms, including being very sensitive to certain sounds as well as being more sensitive than others to loud sounds. The underlying brain activity for sound perception and speech learning in Fragile X is not well understood, especially in the infant and toddler years. This study uses behavioral assessment of speech and language abilities, neuroimaging, and hearing tests to understand how speech and hearing are different 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 data supports the effectiveness of the treatment Speech discrimination, Speech Therapy, Auditory Training for Fragile X Syndrome?

Research indicates that individuals with Fragile X Syndrome have difficulties with auditory processing and speech sound processing, which can impact language development. Speech therapy and auditory training may help improve these areas by targeting the specific auditory and speech challenges identified in studies, such as impaired phonological processing and abnormal neural responses to sounds. ^{1 2 3 4 5}

Is speech discrimination therapy safe for humans?

The research articles provided do not contain specific safety data for speech discrimination therapy or related treatments like speech therapy or auditory training in humans. ^{4 6 7 8 9}

How does the treatment Speech Discrimination differ from other treatments for Fragile X Syndrome?

Speech Discrimination therapy focuses on improving the ability to distinguish and understand speech sounds, which is particularly important for individuals with Fragile X Syndrome who often have difficulties with language development and auditory processing. This approach is unique because it targets the specific auditory processing challenges associated with the syndrome, unlike other treatments that may not address these specific speech and language issues. ^{1 2 3 5 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phonological accuracy and intelligibility in connected speech of boys with fragile X syndrome or Down syndrome. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Development of Neural Response to Novel Sounds in Fragile X Syndrome: Potential Biomarkers. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Degraded speech sound processing in a rat model of fragile X syndrome. [2021]

4. United States 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. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Early Intervention Practices and Communication Intervention Strategies for Young Males With Fragile X Syndrome. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Effects of AFQ056 on language learning in fragile X syndrome. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Auditory brainstem responses in young males with Fragile X syndrome. [2007]

8. England pubmed.ncbi.nlm.nih.gov

FMR1 mRNA from full mutation alleles is associated with ABC-CFX scores in males with fragile X syndrome. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

A Pilot Quantitative Evaluation of Early Life Language Development in Fragile X Syndrome. [2020]

10. United States 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. [2019]