Neurophysiologic Biomarkers in Rett Syndrome
- Conditions
- RTTRett Syndrome, AtypicalRett Syndrome
- Interventions
- Other: EEG and Auditory and Visual Evoked Potentials (AEP and VEP)Other: Clinical assessment
- Registration Number
- NCT05932589
- Lead Sponsor
- Children's Hospital of Philadelphia
- Brief Summary
The goal of this observational study is to identify candidate biomarkers in individuals with Rett Syndrome (RTT). The main questions it aims to answer are:
* Do these biomarkers change during clinical changes in individuals with RTT?
* Are biomarkers stable over time in clinically stable individuals?
* Do these biomarkers correlate with severity of RTT?
Participants will be asked to undergo an electroencephalogram (EEG) with measurements of Evoked Potentials (EP) to measure electrical activity in the brain.
Researchers will compare findings in individuals with RTT to those in typically developing individuals to see if there are differences between the two groups.
- Detailed Description
The main goal of the project is to identify potential biomarkers that can become measures for intervention and other translational studies and, at the same time, provide insight into abnormal synaptic activity and pathogenesis of RTT. Therefore, the proposed assessments will be performed with females with RTT and age matched typically developing females. These electrophysiological assessments will be compared to established clinical outcome measures from previous work in the NIH funded Rett and Rett related disorders natural history study. The neurophysiological parameters for RTT will be correlated with each other and also to disease staging, overall clinical severity scores and through exploratory analyses with specific clinical features. The investigators will also be testing procedures to perform the recordings, electrode types and placement, and ways to reduce movement and artifact within the data to establish best practices.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 202
- Rett Group: Females ages 3-18 (inclusive) with a clinical diagnosis of RTT with a likely pathogenic or known pathogenic variant in MECP2.
- Likely Rett Group: Females from 1 year to < 5 years of age with MECP2 variant if regression has not yet occurred or child is within 6 months of last skill loss.
- Typically developing (TD) Group: Females age matched to RTT population (1-18) with no developmental or cognitive concerns as assessed using the Child/Adult Behavioral Checklist, Survey of Well-Being of Young Children (<5yo), or the Wide Range Achievement Test-4 (>5 yo).
Rett and Likely Rett Groups:
- Presence of a duplication in MECP2 or any other identified pathogenic mutation in another gene.
- Active medical conditions not typically found in RTT.
Typically Developing Group:
- Score below norms on the performance tests
- Have a known neurological disorder (excluding migraine)
- Being on neuroactive medications.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description RTT Females EEG and Auditory and Visual Evoked Potentials (AEP and VEP) Females with Rett Syndrome RTT Females Clinical assessment Females with Rett Syndrome Controls EEG and Auditory and Visual Evoked Potentials (AEP and VEP) Females with typical development
- Primary Outcome Measures
Name Time Method Visual Evoked Potential (VEP) amplitude 5 years N1-P1 amplitude at Oz and other occipital electrodes will be calculated.
Auditory Evoked Potential (AEP) amplitude 5 years Amplitude of P1, P2 and N1 peaks (uV)
EEG Analysis 5 years EEG Root mean square (RMS) amplitude, Amplitude variability, 1/f constant, power bands in typical bands (Delta, theta, alpha, Beta, gamma) and ratios will be calculated.
Auditory Evoked Potential (AEP) latency (ms) 5 years Calculated N1, P1 latencies in Cz and other electrodes \[posterior temporal region (T5/P3/T3) electrodes\], will be used for analysis.
Visual Evoked Potential (VEP) latencies (ms) 5 years The latencies of the N1, P1, and N2 components will be identified primarily at occipital electrodes with Oz will be the primary electrode of analysis. N1-P1 time will be analyzed.
- Secondary Outcome Measures
Name Time Method VEP spectral analysis, dipole determination and spatial distribution 5 years spectral analysis of the individual waveforms, dipole determination of N1 and P1 peaks and spatial distribution of peak values.
AEP spectral analysis, dipole determination and spatial distribution 5 years spectral analysis of the individual waveforms, dipole determination of N1 and P1 peaks and spatial distribution of peak values.
Trial Locations
- Locations (6)
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Boston Children's Hospital
🇺🇸Brookline, Massachusetts, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States