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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to better understand how children with Fragile X Syndrome perceive and learn speech. Researchers will use tests to assess speech and language skills and brain scans to observe how these children process sounds differently. Participants will listen to speech sounds while researchers monitor their brain activity. Children with Fragile X Syndrome or those born prematurely, who can sit independently and speak English at home, might be suitable candidates. This study seeks to explain why speech and hearing are unique in these children. As an unphased study, this trial offers a unique opportunity to contribute to groundbreaking research that could enhance understanding and support for 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 speech discrimination assessment is safe for children with Fragile X Syndrome?

Research has shown that speech discrimination therapy is safe in many situations. Although specific safety data for treating Fragile X Syndrome with this therapy is lacking, no major reports of negative effects have emerged, indicating that the therapy is generally well-tolerated. Speech discrimination therapy involves listening to speech sounds, which is neither invasive nor harmful. In studies, researchers typically measure participants' brain activity to assess how they process these sounds. This process resembles everyday listening and is considered safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new way to understand and potentially help with Fragile X Syndrome through speech discrimination assessments. Unlike traditional treatments that might focus on behavioral therapy or medication, this approach involves participants listening to speech sounds while tracking brain responses. This could provide fresh insights into how the brains of individuals with Fragile X Syndrome process speech, potentially leading to new therapeutic strategies. By measuring electrical and hemodynamic changes in the brain, this study hopes to uncover unique patterns that could pave the way for innovative treatment options in the future.

What evidence suggests that speech discrimination is effective for Fragile X Syndrome?

Research has shown that training to better understand speech can improve talking and language skills in people with Fragile X Syndrome. For example, one study using computer-based listening exercises found that participants improved in recognizing vowel and consonant sounds. This suggests that similar methods might help people with Fragile X understand speech better. Another study using rats with Fragile X found that their brains had trouble processing speech sounds, indicating that focused speech training could help address these issues. Although direct evidence in humans with Fragile X remains limited, these studies suggest that speech training techniques could enhance communication skills. Participants in this trial will engage in speech discrimination exercises, listening to speech sounds while investigators measure electrical and hemodynamic changes in the brain. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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.

Exclusion Criteria

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

You were not born before 36 weeks of pregnancy.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

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

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]

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]

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]

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]

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]

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]

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]

Citations

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withpower.com

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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 ...

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withpower.com

withpower.com/trial/phase-fragile-x-syndrome-9-2022-c2fcb?condition=fragile+x+syndrome&hasNoPlacebo=false&overallStatus=Recruiting

Speech Discrimination 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 ...

3.

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 ...

4.

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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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4849176/

A Spoken Language Intervention for School-Aged Boys with ...

The amount of perseverative speech produced by males with FXS is higher than what is observed for typically developing children matched on language level (Levy ...

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clinicaltrials.gov/study/NCT05957549

Study Details | NCT05957549 | Tracking Early Emergence ...

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

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2898566/

Treatments for Fragile X Syndrome: A Closer Look at the ...

A closer look at the data from those investigations reveals a paucity of evidence that medications can improve intellectual and adaptive functioning in FXS.

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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 ...