Rett Syndrome, MECP2 Duplication, and Rett-Related Disorders Consortium, Rare Disease Clinical Research Network: Neurophysiologic Correlates
Sponsor study identifier
observational
185
1 country
5
Study Start
January 2, 2017
Actual (reported)Primary Completion
July 31, 2021
Actual (reported)Study Completion
July 31, 2021
Actual (reported)The overall purpose of this project is to advance understanding of the neurophysiological features of Rett syndrome (RTT), MECP2 Duplication (MECP2 Dup) and RTT-related disorders (CDKL5, FOXG1) to gain insight into disease pathogenesis, with an emphasis on identifying biomarkers of disease evolution and severity. This specific study is intertwined to the core study Natural History of Rett Syndrome and Related Disorders (RTT5211), which characterizes range of clinical involvement and genotype-phenotype correlations and will provide phenotypical data for determining the clinical relevance of the neurophysiologic parameters; study subjects here are co- and primarily enrolled in RTT5211. The proposed studies will serve as basis of future translational investigations, including further refinement of biomarkers, development of outcome measures, and clinical trials per se.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
July 31, 2021
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Some registry-reported names shown below are not yet linked in this graph.
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
January 2, 2017
Actual (reported)March 1, 2017
Actual (reported)March 10, 2017
Actual (reported)July 31, 2021
Actual (reported)July 31, 2021
Actual (reported)Auditory Event-related potentials
EEG will be filtered between 0.5 and 400Hz. The EEG will be segmented around each stimulus presentation. 200msec prior to 1000msec post each stimulus will be collected and averaged for each trial for each electrode. The electrodes with highest averaged N1 waveforms, predicted to be posterior temporal (T5/P3/T3) electrodes, will be used for subsequent analysis. The averaged waveforms will be analyzed for latency to N1 and P1 peak frm which the auditory event related potentials will be the main parameter for statistical analysis.
3 years
Visual Event-related potentials
VEP analysis will be similar to the AEP analysis. EEG will be prepared using the same methodology but using occipital electrodes with Oz as the primary electrode of analysis. The EEG will be averaged from 200msec prior to 1000ms post stimulus. The N1, P1, and N2 components will be identified and will be averaged and the latency and amplitude of the peaks quantified. P1 latency and N1-P1 time will be the primary end point of the study. The latency will be used for the statistical parameter.
3 years
EEG
For frequency based analysis, 10-20 ten-second epochs of noise free EEG without clear eye blinks during wakefulness and eyes open; 10 ten-second epochs of wakefulness and eyes closed (assessed by video); and 10-20 ten-second epochs of EEG during each stage of sleep will be analyzed. A prescreen of EEG using a template matching algorithm (EEGlab) can be used to reduce amount of data to be reviewed. For theta and gamma band activity, the EEG will be band passed filtered between 2-10 and 25-70Hz, respectively, and a FFT performed on the filtered data. Spike location, frequency, and activity (change with sleep, eye closure, stimulation) will be calculated.
Auditory and Visual event-related potentials (ERP) and EEG in 60 individuals with Rett syndrome.
Auditory and Visual event-related potentials (ERP) and EEG in 18 individuals with MECP2 Duplication syndrome.
Auditory and Visual event-related potentials (ERP) and EEG in 18 individuals with CDKL5 syndrome and 14 individuals with FOXG1 syndrome.
Auditory and Visual event-related potentials (ERP) and EEG in 60 Control individuals (30 males and 30 females).
Specifically, through up to three standardized sessions (i.e., annual \[every 10-14 months\]), we will assess AEP and VEP. ERP recordings will also provide data for specific rhythms/band (gamma and alpha) pattern analyses as secondary measures as well as technical control data, which will help to exclude those with co-current seizures.
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
Individuals with RTT, MECP2 Dup, and RTT-related disorders (mutations or deletions in CDKL5 and FOXG1 genes) who are also enrolled in the RTT5211 Protocol, which collects longitudinal clinical and neurobehavioral data in the above mentioned disorders. Participants will be linked to the RTT5211 Protocol by their RDCRN identification numbers. All participants will be tested for MECP2, CDKL5, and/or FOXG1 mutations; those with RTT phenotype will be assessed in terms of diagnostic criteria for classic or atypical RTT. No phenotypic selection will be performed; the cohort will be representative of each disorder. 60 typically developing girls and boys (30 each) will be enrolled to serve as controls for all three cohorts with age matching to the RTT/CDKL5 girls and MECP2 Dup/FOXG1 boy cohorts.
University of Colorado Denver
Denver, Colorado, 80045-2571, United States
Boston Children's Hospital
Boston, Massachusetts, 02115-5724, United States
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4318, United States
Vanderbilt University
Nashville, Tennessee, 37212, United States
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Eric Marsh, MD, PhD
Children's Hospital of Philadelphia
185 participants (actual enrollment reported by the registry).
First Submitted
March 1, 2017
First Posted
March 10, 2017
Study Start
January 2, 2017
Actual (reported)3 years
Contact the study team to confirm eligibility.
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Primary Completion
July 31, 2021
Actual (reported)Study Completion
July 31, 2021
Actual (reported)Last Updated
August 5, 2021
Record last verified: 2021-08
Data will be submitted to NDAR/dbGAP.
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