Neurophysiologic Biomarkers in Rett Syndrome

NCT05932589 | Recruiting

• 2 other identifiers: 22-0206331R61NS130216-01
• Study Type: observational
• Target: 202
• Locations: 1 country
• Sites: 6

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.

Conditions

Rett Syndrome; RTT; Rett Syndrome, Atypical

Keywords

Biomarker; EEG; Evoked Potentials; MECP2

Outcome Measures

Primary Outcomes (5)

• Auditory Evoked Potential (AEP) latency (ms)

  Calculated N1, P1 latencies in Cz and other electrodes \[posterior temporal region (T5/P3/T3) electrodes\], will be used for analysis.

  5 years

• Auditory Evoked Potential (AEP) amplitude

  Amplitude of P1, P2 and N1 peaks (uV)

  5 years

• Visual Evoked Potential (VEP) latencies (ms)

  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.

  5 years

• Visual Evoked Potential (VEP) amplitude

  N1-P1 amplitude at Oz and other occipital electrodes will be calculated.

  5 years

• EEG Analysis

  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.

  5 years

Secondary Outcomes (2)

• AEP spectral analysis, dipole determination and spatial distribution

  5 years

• VEP spectral analysis, dipole determination and spatial distribution

  5 years

Study Arms (2)

RTT Females

Females with Rett Syndrome

Other: EEG and Auditory and Visual Evoked Potentials (AEP and VEP); Other: Clinical assessment

Controls

Females with typical development

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

Interventions

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

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

Controls; RTT Females

Clinical assessment OTHER

Established clinical measures for RTT will be collected for RTT participants

RTT Females

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Enrolled participants with Rett syndrome will include individuals receiving clinical care through the Rett Syndrome clinics at participating sites. Typically developing individuals will be recruited using study recruitment centers or family members of Rett participants at each site. Each of the sites are International Rett Syndrome Foundation Centers of Excellence (Rettsyndrome.org).

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Vanderbilt University Medical Center: collaborator

Study Sites (6)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Boston Children's Hospital

Brookline, Massachusetts, 02445, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Related Publications (3)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Rett Syndrome; Rett Syndrome, Atypical

Interventions

Evoked Potentials, Visual; asparaginylendopeptidase

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Intervention Hierarchy (Ancestors)

Evoked Potentials; Cortical Excitability; Electrophysiological Phenomena; Physiological Phenomena; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Ocular Physiological Phenomena

Study Officials

• Eric Marsh, MD, PhD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

• Jeffrey Neul, MD, PhD

  Vanderbilt University Medical Cener

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Holly Dubbs, MS. CGC

CONTACT

215-590-1719; dubbsh@chop.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2023
• First Posted: July 6, 2023
• Study Start: October 11, 2023
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Time Frame: Available data from this observational study will be released to the repository and will become available to the scientific community one year after publication of planned analyses, or after a period of 5 years from the date when the data were collected, whichever comes first.
• Access Criteria: National Institute of Mental Health (NIMH) Data Archive (NDA) policy will govern access criteria.

Locations

US (6)