Speech Discrimination Assessments 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, 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.
12345Is 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.
13678How 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.
12359Eligibility 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.
Trial 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
Participant Groups
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.
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
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.
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.
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.
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.
A Retrospective Video Analysis of Canonical Babbling and Volubility in Infants with Fragile X Syndrome at 9-12 Months of Age. [2023]An infant's vocal capacity develops significantly during the first year of life. Research suggests early measures of pre-speech development, such as canonical babbling and volubility, can differentiate typical versus disordered development. This study offers a new contribution by comparing early vocal development in 10 infants with Fragile X syndrome and 14 with typical development. Results suggest infants with Fragile X syndrome produce fewer syllables and have significantly lower canonical babbling ratios compared to infants who are typically developing. Furthermore, the particular measures of babbling were strong predictors of group membership, adding evidence regarding the possible utility of these markers in early identification.
Development of an expressive language sampling procedure in fragile X syndrome: a pilot study. [2022]There is a great need for valid outcome measures of functional improvement for impending clinical trials of targeted interventions for fragile X syndrome (FXS). Families often report conversational language improvement during clinical treatment, but no validated measures exist to quantify this outcome. This small-scale study sought to determine the feasibility, reproducibility, and clinical validity of highly structured expressive language sampling as an outcome measure reflecting language ability.
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.
Double-blind, placebo-controlled crossover study of folinic acid (Leucovorin for the treatment of fragile X syndrome. [2013]We conducted a randomized, double-blind, placebo-controlled crossover study of folinic acid therapy (dl-Leucovorin, 15 mg/day) or placebo for males with Fragile X (fra(x)) syndrome. Twenty-one patients were enrolled in the study. The treatment periods were 3 months in length. Patients were followed with chemistry panels and complete blood counts. No differences between placebo and treatment phases were noted in any laboratory parameter. Instruments to measure functioning were the Vineland Adaptive Behavioral Scales, Peabody Picture Vocabulary Test-Revised, Conners Parent and Teaching Rating Scales, the ADD-H: Comprehensive Teacher's Rating Scales (ACTeRS), and a questionnaire designed by the investigators. At the crossover point, 2 parents requested to withdraw from the study because they felt their children had made dramatic gains during the first half of the study and had lost those gains after the crossover point. Both parents had accurately predicted that their sons were receiving folinic acid during the first half of the study. However, no statistically significant differences could be demonstrated between the treatment and placebo phases of the study with any instrument when the results were averaged over the entire cohort. After the conclusion of the study, approximately one-half of the parents believed that their children had benefitted from the folinic acid therapy and elected to continue treatment. Thus far, no significant side effects have been noted from long-term folinic acid therapy so we are offering all Fragile X patients a 3-month trial of medication.
Word retrieval difficulty in adult females with the FMR1 premutation: Changes over time and across contexts. [2022]Individuals with a premutation of the fragile X mental retardation (FMR1) gene are at risk for a variety of psychological, physical, and cognitive issues, including difficulty with word retrieval. The present study examined three indicators of word retrieval difficulty; reduced productivity, reduced lexical diversity, and increased errors in word retrieval in a group of 38 female premutation carriers during standard-length speech samples collected over a period of eight years. Our results revealed that as women aged, they produced fewer words, produced fewer different words, and had greater word retrieval errors. In addition, the rate of word retrieval errors was highly correlated between two speaking contexts, indicating that this difficulty was pervasive and not solely the result of speaking in monologue. Our results suggest that subtle areas of cognitive decline emerge at a much earlier age among female premutation carriers than would be expected during healthy aging.