Speech Discrimination for Fragile X Syndrome
Recruiting in Palo Alto (17 mi)
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Children's Hospital Medical Center, Cincinnati
Disqualifiers: Seizures, Premature birth, others
No Placebo Group
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.12345
Is speech discrimination therapy safe for humans?
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.123510
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.
Trial 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 (Behavioural Intervention)
Trial OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: Speech SoundsExperimental Treatment1 Intervention
Participants listen to speech sounds while the investigators measure electrical and hemodynamic changes in the brain.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cincinnati Children's HospitalCincinnati, OH
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Who Is Running the Clinical Trial?
Children's Hospital Medical Center, CincinnatiLead Sponsor
References
Phonological accuracy and intelligibility in connected speech of boys with fragile X syndrome or Down syndrome. [2021]To compare the phonological accuracy and speech intelligibility of boys with fragile X syndrome with autism spectrum disorder (FXS-ASD), fragile X syndrome only (FXS-O), Down syndrome (DS), and typically developing (TD) boys.
Development of Neural Response to Novel Sounds in Fragile X Syndrome: Potential Biomarkers. [2022]Auditory processing abnormalities in fragile X syndrome (FXS) may contribute to difficulties with language development, pattern identification, and contextual updating. Participants with FXS (N = 41) and controls (N = 27) underwent auditory event-related potentials during presentation of an oddball paradigm. Data was adequate for analysis for 33 participants with FXS and 27 controls (age 4-51 y, 13 females [FXS]; 4-54 y, 11 females [control]). Participants with FXS showed larger N1 and P2 amplitudes, abnormal lack of modulation of P1 and P2 amplitudes and P2 latency in response to oddball stimuli ) relative to controls: Females with FXS were more similar to controls. Participants with FXS showed a marginal speeding of the P2 latency, suggesting potentiation to oddball stimuli rather than habituation. Participants with FXS showed a heightened N1 habituation effect compared to controls. Gamma power was significantly higher for participants with FXS. Groups did not differ on mismatch negativity. Both controls and participants with FXS showed similar developmental trajectories in P1 and N1 amplitude, P2 latency, and gamma power, but not for P2 amplitude. One month retest analyses performed in 14 participants suggest strong test-retest reliability for most measures. Individuals with FXS show previously demonstrated increased response amplitude and high frequency neural activity. Despite an overall normal developmental trajectory for most measures, individuals with FXS show age-independent but gender-dependent decreases in complex processing of novel stimuli. Many markers show strong retest reliability even in children and thus are potential biomarkers for clinical trials in FXS.
Degraded speech sound processing in a rat model of fragile X syndrome. [2021]Fragile X syndrome is the most common inherited form of intellectual disability and the leading genetic cause of autism. Impaired phonological processing in fragile X syndrome interferes with the development of language skills. Although auditory cortex responses are known to be abnormal in fragile X syndrome, it is not clear how these differences impact speech sound processing. This study provides the first evidence that the cortical representation of speech sounds is impaired in Fmr1 knockout rats, despite normal speech discrimination behavior. Evoked potentials and spiking activity in response to speech sounds, noise burst trains, and tones were significantly degraded in primary auditory cortex, anterior auditory field and the ventral auditory field. Neurometric analysis of speech evoked activity using a pattern classifier confirmed that activity in these fields contains significantly less information about speech sound identity in Fmr1 knockout rats compared to control rats. Responses were normal in the posterior auditory field, which is associated with sound localization. The greatest impairment was observed in the ventral auditory field, which is related to emotional regulation. Dysfunction in the ventral auditory field may contribute to poor emotional regulation in fragile X syndrome and may help explain the observation that later auditory evoked responses are more disturbed in fragile X syndrome compared to earlier responses. Rodent models of fragile X syndrome are likely to prove useful for understanding the biological basis of fragile X syndrome and for testing candidate therapies.
Sensory Symptoms and Signs of Hyperarousal in Individuals with Fragile X Syndrome: Findings from the FORWARD Registry and Database Multisite Study. [2023]This study was designed to increase our understanding about characteristics and the impact of sensory symptoms (SS) and signs of hyperarousal (HA) in individuals with fragile X syndrome (FXS) from childhood through early adulthood and by gender. Data derived from the Fragile X Online Registry With Accessible Research Database (FORWARD), a natural history study of FXS, were analyzed using descriptive statistics and multivariate linear and logistic regression models to examine SS and signs of HA, their impact on behavioral regulation and limitations on the subject/family. The sample (N = 933) consisted of 720 males and 213 females. More males were affected with SS (87% vs. 68%) and signs of HA (92% vs. 79%). Subjects who were endorsed as having a strong sensory response had more comorbidities, including behavioral problems. The predominant SS was difficulty with eye gaze that increased with age in both genders. As individuals age, there was less use of non-medication therapies, such as occupational therapy (OT)/physical therapy (PT), but there was more use of psychopharmacological medications and investigational drugs for behaviors. Multiple regression models suggested that endorsing SS and signs of HA was associated with statistically significantly increased ABC-C-I subscale scores and limited participation in everyday activities. This study improves our understanding of SS and signs of HA as well as their impact in FXS. It supports the need for more research regarding these clinical symptoms, especially to understand how they contribute to well-known behavioral concerns.
Early Intervention Practices and Communication Intervention Strategies for Young Males With Fragile X Syndrome. [2019]This study describes speech-language pathologists' impressions of the communication difficulties of young males with fragile X syndrome (FXS) and the need for both syndrome-specific and individualized interventions. The findings of a regional study that identified speech-language pathologists' impressions of the speech, language, and behavioral difficulties experienced by males with FXS and an array of interventions used by speech-language pathologists to improve communication skills for these children are reported.
Effects of AFQ056 on language learning in fragile X syndrome. [2023]FXLEARN, the first-ever large multi-site trial of effects of disease-targeted pharmacotherapy on learning, was designed to explore a new paradigm for measuring effects of mechanism-targeted treatment in fragile X syndrome (FXS). In FXLEARN, the effects of mGluR5 negative allosteric modulator (NAM) AFQ056 on language learning were evaluated in 3-6 year-old children with FXS, expected to have more learning plasticity than adults, where prior trials of mGluR5 NAMs have failed.
Auditory brainstem responses in young males with Fragile X syndrome. [2007]Fragile X syndrome (FXS) is the most common inherited cause of mental retardation resulting in developmental delays in males. Atypical outer ear morphology is characteristic of FXS and may serve as a marker for abnormal auditory function. Despite this abnormality, studies of the hearing of young males with FXS are generally lacking. A few studies have suggested that a significant proportion of individuals with FXS demonstrate prolonged auditory brainstem response (ABR) latencies. The purpose of this study was to determine whether young males with FXS display atypical auditory brainstem function compared to typically developing males when conductive and sensorineural hearing loss are ruled out as possible contributors to atypical findings. Participants were 23 males with FXS, 21 typically developing males who were matched for developmental age, and 17 typically developing males who were matched for chronological age. A battery of tests to assess peripheral hearing, cochlear function, and auditory pathway integrity through the level of the brainstem was completed. Males with FXS were similar to typically developing males who were matched for developmental age level or chronological age level on all measures. They had normal hearing sensitivity and middle ear function and scored similar to the typically developing children on the measures of auditory brainstem pathway integrity. In summary, ABRs in young males with FXS were within normal limits.
FMR1 mRNA from full mutation alleles is associated with ABC-CFX scores in males with fragile X syndrome. [2021]Fragile X syndrome (FXS) is caused by a hypermethylated full mutation (FM) expansion with ≥ 200 CGG repeats, and a decrease in FMR1 mRNA and its protein. However, incomplete silencing from FM alleles has been associated with more severe autism features in FXS males. This study compared scores on the Aberrant Behavior Checklist-Community-FXS version (ABC-CFX) in 62 males affected with FXS (3 to 32 years) stratified based on presence or absence of mosaicism and/or FMR1 mRNA silencing. Associations between ABC-CFX subscales and FMR1 mRNA levels, assessed using real-time PCR relative standard curve method, were also examined. The FXS group mosaic for premutation (PM: 55-199 CGGs) and FM alleles had lower irritability (p = 0.014) and inappropriate speech (p < 0.001) scores compared to males with only FM alleles and complete loss of FMR1 mRNA. The PM/FM mosaic group also showed lower inappropriate speech scores compared to the incomplete silencing (p = 0.002) group. Increased FMR1 mRNA levels were associated with greater irritability (p < 0.001), and lower health-related quality of life scores (p = 0.004), but only in the incomplete silencing FM-only group. The findings suggest that stratification based on CGG sizing and FMR1 mRNA levels may be warranted in future research and clinical trials utilising ABC-CFX subscales as outcome measures.
A Pilot Quantitative Evaluation of Early Life Language Development in Fragile X Syndrome. [2020]Language delay and communication deficits are a core characteristic of the fragile X syndrome (FXS) phenotype. To date, the literature examining early language development in FXS is limited potentially due to barriers in language assessment in very young children. The present study is one of the first to examine early language development through vocal production and the language learning environment in infants and toddlers with FXS utilizing an automated vocal analysis system. Child vocalizations, conversational turns, and adult word counts in the home environment were collected and analyzed in a group of nine infants and toddlers with FXS and compared to a typically developing (TD) normative sample. Results suggest infants and toddlers with FXS are exhibiting deficits in their early language skills when compared to their chronological expectations. Despite this, when accounting for overall developmental level, their early language skills appear to be on track. Additionally, FXS caregivers utilize less vocalizations around infants and toddlers with FXS; however, additional research is needed to understand the true gap between FXS caregivers and TD caregivers. These findings provide preliminary information about the early language learning environment and support for the feasibility of utilizing an automated vocal analysis system within the FXS population that could ease data collection and further our understanding of the emergence of language development.
A comparison of language characteristics of mentally retarded adults with fragile X syndrome and those with nonspecific mental retardation and autism. [2019]Fragile X syndrome is a recently identified form of mental retardation that is associated with a chromosomal abnormality and inherited in an X-linked manner. Previous studies have suggested that distinctive speech and language characteristics are associated with the syndrome. Twelve adult male residents of an institution for the retarded (aged 23 to 51 years) were compared on a series of speech and language measures to 12 adult males with nonspecific forms of MR who were residents of the same institution and were matched on age and IQ. A second contrast group consisted of similarly matched autistic men. Results revealed that there were no significant differences among the groups' performance, with the exception of increased rates of echolalia in the autistic group. A nonsignificant trend toward poorer performance on expressive measures on the part of the fragile X group was noted. The implications of these findings for further research on the syndrome are discussed.