Characterization of Translatable Neurophysiological Biomarkers to Enhance Therapeutic Development in Rett Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 202
- 试验地点
- 6
- 主要终点
- Auditory Evoked Potential (AEP) amplitude
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Year 至 18 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Rett Group: Females ages 3-18 (inclusive) with a clinical diagnosis of RTT with a likely pathogenic or known pathogenic variant in MECP
- •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).
排除标准
- •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.
结局指标
主要结局
Auditory Evoked Potential (AEP) amplitude
时间窗: 5 years
Amplitude of P1, P2 and N1 peaks (uV)
Visual Evoked Potential (VEP) amplitude
时间窗: 5 years
N1-P1 amplitude at Oz and other occipital electrodes will be calculated.
EEG Analysis
时间窗: 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)
时间窗: 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)
时间窗: 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.
次要结局
- VEP spectral analysis, dipole determination and spatial distribution(5 years)
- AEP spectral analysis, dipole determination and spatial distribution(5 years)