Tracking Early Emergence of Sound Perception Impairments in FXS With Multimodal fNIRS/EEG

Fragile X Syndrome Clinical Trial

Official title:

Tracking Early Emergence of Sound Perception Impairments in FXS With Multimodal fNIRS/EEG

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05957549
• Other study ID #: K23HD109375
• Status: Recruiting
• Phase: N/A
• Start date: October 4, 2022
• Est. completion date: August 31, 2027

Study information

• Verified date: July 2023
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Elizabeth Smith, PhD
• Phone: 5135171383
• Email: elizabeth.smith3[@]cchmc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

Fragile X Syndrome (FXS) is the leading monogenic cause of intellectual disability and autism and is associated with extremely high risk for early delays in speech and language. While the infant years are essential to speech and language development, neural mechanisms for language impairments have been studied entirely in older children and adults with FXS. Therefore, markers for speech and language impairments are unavailable in infants and young children with FXS to predict severity, test potential mechanisms, and track response to intervention. The investigators have identified a hallmark brain-based phenotype of hyperresponsiveness to sounds in adolescents and adults with FXS. This fundamental alteration in cortical responses to sound could influence early language delays, but this phenotype has not been explored in infants or toddlers with FXS.

Specifically, in this study the investigators will use simultaneous EEG/fNIRS during presentation of simple speech, stories, and nonspeech sounds to quantify and localize auditory hypersensitivity and neural differentiation in 30 preschoolers with FXS. The investigators will assess specificity through comparison with 30 typically developing controls and 30 mental-age matched children with a history of premature birth and language delays. In addition, the investigators will complete a longitudinal study (3 timepoints) of 15 infants with FXS and 15 TDC controls, with the first visit completed between 6 and 12 months of age. At each visit, the investigators will measure speech and hearing alongside cortical responses to sounds. In combination with quantitative assessment of linguistic complexity in each infant's home environment, the investigators will develop a potential model linking brain-based indicators with emergence of language delays in FXS

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: August 31, 2027
• Est. primary completion date: September 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 5 Years

Eligibility

Inclusion Criteria:

• Diagnoses of Fragile X Syndrome, Typical Development, or History of Premature Birth

• able to sit independently

• English is spoken at home

Exclusion Criteria:

• For all participants: no seizures in the past 6 months

• For typical development group and Fragile X group: not born prior to 36 weeks gestation

Related Conditions & MeSH terms

• Fragile X Syndrome

Intervention

Other:
• Speech discrimination
Two different speech sounds are played at the same sound intensity.

Locations

Country	Name	City	State
United States	Cincinnati Children'S Hospital	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Mullen Scales of Early Learning	change in Mullen Scales scores (age-corrected) from baseline on all subscales, including Expressive Language, Receptive Language, FIne Motor, Gross Motor, and Visual Reception. T-Scores from the Mullen Scales of Early Learning (MSEL) have a mean of 50 and a standard deviation of 10. Range=20-80. Higher scores indicate more advanced developmental skills.	at 6 month, 12 month, 18 month, 24 month, 3 year, and 4 year visits
Primary	Changes in oxygenated and deoxygenated hemoglobin concentration in response to sounds in language regions of the brain	Relative increase in oxygenated versus deoxygenated hemoglobin for no sounds, low intensity sounds, and medium intensity sounds. Measured via functional Near Infrared Spectroscopy with optodes placed over frontal, temporal, and parietal language regions.	at 6 month, 12 month, 18 month, 24 month, 3 year, and 4 year visits
Primary	Changes in amplitude of mismatch negativity response during sound discrimination	Electroencephalography is measured over the scalp while participant listens to speech sounds with infrequent "oddball" stimuli. Amplitude of the P100 for all stimuli as well as amplitude of the mismatch negativity response (frequent minus infrequent response) as well as change in these metrics over development are tracked in all groups.	at 6 month, 12 month, 18 month, 24 month, 3 year, and 4 year visits
Primary	Changes in LENA vocalizations and conversational turns	LENA is a voice recording system and proprietary program that records a child's home language environment and quantifies number of sounds and words each child produces as well as complexity of home language environment via number of conversational turns between the child and parents.	at 6 month, 12 month, 18 month, 24 month, 3 year, and 4 year visits
Primary	Changes in hearing thresholds	Hearing thresholds in dB as assessed using Conditioned Play Audiometry (CPA) or Visual Reinforced Audiometry (VRA) dependent on child age and developmental ability.	at 6 month, 12 month, 18 month, 24 month, 3 year, and 4 year visits
Primary	Otoacoustic Emissions (OAEs)	Signals produced by excitation of hair cells in cochlea are measured for a range of frequencies.	At first study visit
Primary	Changes in tympanometric pressure profile in the inner ear	Wide Band Tympanometry is completed to measure variability in tympanometric pressure for left and right ears that may affect hearing profile.	at 6 month, 12 month, 18 month, 24 month, 3 year, and 4 year visits
Secondary	Sensory profile 2 Auditory Processing subtest	parent-report measure of child's behavioral responses to sounds in their environment	at 6 month, 12 month, 18 month, 24 month, 3 year, and 4 year visits
Secondary	Sensory Profile 2 Attentional subtest	parent-report measure of child's awareness of and responses to sensory cues in their environment.	at 6 month, 12 month, 18 month, 24 month, 3 year, and 4 year visits