Speech Discrimination Assessments 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: 1

90 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, toddler, and preschool 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 shows that individuals with Fragile X Syndrome have difficulties with auditory processing, which can affect language development. Speech therapy and auditory training may help improve these skills by targeting the brain's response to sounds, as seen in studies where individuals with Fragile X Syndrome showed changes in neural activity related to sound processing. ^{1 2 3 4 5}

Is speech discrimination therapy safe for humans?

The research does not provide specific safety data for speech discrimination therapy, but no significant side effects were noted in a related study on folinic acid therapy for Fragile X syndrome, suggesting that treatments in this area may generally be safe. ^{1 3 6 7 8}

How does this treatment for Fragile X Syndrome differ from other treatments?

This treatment focuses on assessing speech discrimination, which is unique because it targets the specific auditory processing abnormalities in Fragile X Syndrome that contribute to language development difficulties. Unlike other treatments that may address broader symptoms, this approach aims to understand and potentially improve the neural response to novel sounds, which could be a novel way to enhance communication skills in individuals with Fragile X Syndrome. ^{1 2 3 5 9}

Eligibility Criteria

This trial is for children who have Fragile X Syndrome, can sit by themselves, and come from homes where English is spoken. It's also open to those with typical development or a history of premature birth. Children who've had seizures in the last six months or were born before 36 weeks (except for preemies) cannot participate.

Inclusion Criteria

I can sit up by myself without help.

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

I speak English at home.

Exclusion Criteria

You were not born before 36 weeks of pregnancy.

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

Assessment

Participants undergo behavioral assessment of speech and language abilities, neuroimaging, and hearing tests using EEG/fNIRS during presentation of speech and nonspeech sounds.

Single visit

1 visit (in-person)

Follow-up

Participants are monitored for changes in developmental skills and auditory processing through outcome measures.

4 weeks

Treatment Details

Interventions

• Speech discrimination

Trial Overview The study investigates how kids with Fragile X Syndrome process sounds and learn speech. It involves behavioral assessments, brain imaging (fNIRS/EEG), and hearing tests to compare their abilities with typically developing children.

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

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]

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]

Infants with Fragile X syndrome show significantly reduced vocal development, producing fewer syllables and having lower canonical babbling ratios compared to typically developing infants, based on a study of 24 infants (10 with Fragile X and 14 typically developing).

The study indicates that early vocal measures, such as babbling, can effectively differentiate between typical and disordered development, suggesting their potential use in early identification of developmental issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Video Analysis of Canonical Babbling and Volubility in Infants with Fragile X Syndrome at 9-12 Months of Age. Belardi, K., Watson, LR., Faldowski, RA., et al.[2023]

The study tested expressive language sampling as a potential outcome measure for assessing language ability in 36 verbal participants with fragile X syndrome (FXS), showing that the tasks were feasible and reproducible.

Results indicated high reliability of the measures used, with strong correlations to established language assessments, suggesting that these tasks could effectively quantify language improvements in future clinical trials for FXS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of an expressive language sampling procedure in fragile X syndrome: a pilot study. Berry-Kravis, E., Doll, E., Sterling, A., et al.[2022]

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 randomized, double-blind, placebo-controlled crossover study involving 21 males with Fragile X syndrome, folinic acid therapy did not show statistically significant improvements in functioning compared to placebo, despite some parents reporting perceived benefits during the treatment phase.

No significant side effects were observed from long-term folinic acid therapy, leading researchers to offer a 3-month trial of the medication to all Fragile X patients, indicating a potential for safe use even if efficacy remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, placebo-controlled crossover study of folinic acid (Leucovorin for the treatment of fragile X syndrome. Strom, CM., Brusca, RM., Pizzi, WJ.[2013]

The study of 38 female carriers of the FMR1 gene premutation over eight years found that as they aged, they experienced significant declines in word retrieval abilities, evidenced by fewer words spoken, reduced variety in word choice, and increased errors.

These findings indicate that cognitive decline related to word retrieval begins earlier in life for female premutation carriers than typically expected in healthy aging, highlighting the need for early intervention and support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Word retrieval difficulty in adult females with the FMR1 premutation: Changes over time and across contexts. Bredin-Oja, SL., Warren, SF., Swinburne Romine, RE., et al.[2022]

References

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

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

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

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

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

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

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

A Retrospective Video Analysis of Canonical Babbling and Volubility in Infants with Fragile X Syndrome at 9-12 Months of Age. [2023]

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

Development of an expressive language sampling procedure in fragile X syndrome: a pilot study. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Double-blind, placebo-controlled crossover study of folinic acid (Leucovorin for the treatment of fragile X syndrome. [2013]

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

Word retrieval difficulty in adult females with the FMR1 premutation: Changes over time and across contexts. [2022]