Neurophysiologic Biomarkers in Rett Syndrome

NCT ID: NCT05932589

Last Updated: 2025-10-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

202 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-10-11

Study Completion Date

2029-03-31

Brief Summary

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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

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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.

Conditions

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Rett Syndrome RTT Rett Syndrome, Atypical

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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RTT Females

Females with Rett Syndrome

EEG and Auditory and Visual Evoked Potentials (AEP and VEP)

Intervention Type OTHER

Through up to eight standardized sessions, participants will undergo AEP and VEP, as well as resting state EEG.

Clinical assessment

Intervention Type OTHER

Established clinical measures for RTT will be collected for RTT participants

Controls

Females with typical development

EEG and Auditory and Visual Evoked Potentials (AEP and VEP)

Intervention Type OTHER

Through up to eight standardized sessions, participants will undergo AEP and VEP, as well as resting state EEG.

Interventions

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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.

Intervention Type OTHER

Clinical assessment

Established clinical measures for RTT will be collected for RTT participants

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Rett Group: Females ages 3-18 (inclusive) with a clinical diagnosis of RTT with a likely pathogenic or known pathogenic variant in MECP2.
2. 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.
3. 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).

Exclusion Criteria

Rett and Likely Rett Groups:

1. Presence of a duplication in MECP2 or any other identified pathogenic mutation in another gene.
2. Active medical conditions not typically found in RTT.

Typically Developing Group:

1. Score below norms on the performance tests
2. Have a known neurological disorder (excluding migraine)
3. Being on neuroactive medications.
Minimum Eligible Age

1 Year

Maximum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eric Marsh, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Jeffrey Neul, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Cener

Locations

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Children's Hospital of Los Angeles

Los Angeles, California, United States

Site Status RECRUITING

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Boston Children's Hospital

Brookline, Massachusetts, United States

Site Status RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

Texas Children's Hospital

Houston, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Holly Dubbs, MS. CGC

Role: CONTACT

215-590-1719

Facility Contacts

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Holly Dubbs, MS, CGC

Role: primary

215-590-1719

Nicole Thompson

Role: primary

615-343-4586

References

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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.

Reference Type BACKGROUND
PMID: 32547374 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33480039 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26332183 (View on PubMed)

Other Identifiers

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1R61NS130216-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

22-020633

Identifier Type: -

Identifier Source: org_study_id

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