Clinical trial NCT05932589: Neurophysiologic Biomarkers in Rett Syndrome
Official title: Characterization of Translatable Neurophysiological Biomarkers to Enhance Therapeutic Development in Rett Syndrome
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Rett Syndrome
RTT
Rett Syndrome, Atypical
Keywords: Biomarker
EEG
Evoked Potentials
MECP2
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Vanderbilt University Medical Center
First posted: 2023-07-06
Enrollment: 202
Sex: FEMALE
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Auditory Evoked Potential (AEP) latency (ms)
timeFrame: 5 years
measure: Auditory Evoked Potential (AEP) amplitude
timeFrame: 5 years
measure: Visual Evoked Potential (VEP) latencies (ms)
timeFrame: 5 years
measure: Visual Evoked Potential (VEP) amplitude
timeFrame: 5 years
measure: EEG Analysis
timeFrame: 5 years
Secondary outcomes:
measure: AEP spectral analysis, dipole determination and spatial distribution
timeFrame: 5 years
measure: VEP spectral analysis, dipole determination and spatial distribution
timeFrame: 5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Brookline
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Eric Marsh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University Medical Cener
name: Jeffrey Neul, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.