Neurophysiologic Biomarkers in Rett Syndrome

Официальное название

Characterization of Translatable Neurophysiological Biomarkers to Enhance Therapeutic Development in Rett Syndrome

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое EEG and Auditory and Visual Evoked Potentials (AEP and VEP)
  Through up to eight standardized sessions, participants will undergo AEP and VEP, as well as resting state EEG.
• Другое Clinical assessment
  Established clinical measures for RTT will be collected for RTT participants

Первичные конечные точки

• Auditory Evoked Potential (AEP) latency (ms) [Срок оценки: 5 years]
• Auditory Evoked Potential (AEP) amplitude [Срок оценки: 5 years]
• Visual Evoked Potential (VEP) latencies (ms) [Срок оценки: 5 years]
• Visual Evoked Potential (VEP) amplitude [Срок оценки: 5 years]
• EEG Analysis [Срок оценки: 5 years]

Вторичные конечные точки (2)

• AEP spectral analysis, dipole determination and spatial distribution [Срок оценки: 5 years]
• VEP spectral analysis, dipole determination and spatial distribution [Срок оценки: 5 years]

Критерии участия

Критерии включения

• 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).

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

США · 6 центров

• Children's Hospital of Los Angeles — Los Angeles
• Children's Hospital Colorado — Aurora
• Boston Children's Hospital — Brookline
• Children's Hospital of Philadelphia — Philadelphia
• Vanderbilt University Medical Center — Nashville
• Texas Children's Hospital — Houston

Публикации

• Saby JN, Peters SU, Roberts TPL, Nelson CA, Marsh ED. Evoked Potentials and EEG Analysis in Rett Syndrome and Related Developmental Encephalopathies: Towards a Biomarker for Translational Research. Front Integr Neurosci. 2020 May 28;14:30. doi: 10.3389/fnint.2020.00030. eCollection 2020. PMID 32547374
• Saby JN, Benke TA, Peters SU, Standridge SM, Matsuzaki J, Cutri-French C, Swanson LC, Lieberman DN, Key AP, Percy AK, Neul JL, Nelson CA, Roberts TPL, Marsh ED. Multisite Study of Evoked Potentials in Rett Syndrome. Ann Neurol. 2021 Apr;89(4):790-802. doi: 10.1002/ana.26029. Epub 2021 Feb 4. PMID 33480039
• LeBlanc JJ, DeGregorio G, Centofante E, Vogel-Farley VK, Barnes K, Kaufmann WE, Fagiolini M, Nelson CA. Visual evoked potentials detect cortical processing deficits in Rett syndrome. Ann Neurol. 2015 Nov;78(5):775-86. doi: 10.1002/ana.24513. Epub 2015 Sep 18. PMID 26332183

Идентификаторы

NCT: NCT05932589 · 22-020633 · 1R61NS130216-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗