Neurophysiologic Biomarkers in Rett Syndrome

Rett Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05932589
• Other study ID #: 22-020633
• Secondary ID: 1R61NS130216-01
• Status: Recruiting
• Start date: October 11, 2023
• Est. completion date: March 31, 2029

Study information

• Verified date: November 2023
• Source: Children's Hospital of Philadelphia
• Contact: Holly Dubbs, MS. CGC
• Phone: 215-590-1719
• Email: dubbsh[@]chop.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 202
• Est. completion date: March 31, 2029
• Est. primary completion date: March 31, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 1 Year to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Rett Syndrome
• RTT
• Syndrome

Intervention

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

Locations

Country	Name	City	State
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Boston Children's Hospital	Brookline	Massachusetts
United States	Texas Children's Hospital	Houston	Texas
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia	National Institute of Neurological Disorders and Stroke (NINDS), Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Auditory Evoked Potential (AEP) amplitude	Amplitude of P1, P2 and N1 peaks (uV)	5 years
Primary	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
Primary	Visual Evoked Potential (VEP) amplitude	N1-P1 amplitude at Oz and other occipital electrodes will be calculated.	5 years
Primary	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	AEP spectral analysis, dipole determination and spatial distribution	spectral analysis of the individual waveforms, dipole determination of N1 and P1 peaks and spatial distribution of peak values.	5 years
Secondary	VEP spectral analysis, dipole determination and spatial distribution	spectral analysis of the individual waveforms, dipole determination of N1 and P1 peaks and spatial distribution of peak values.	5 years