Rett SyndromeNCT05932589
Neurophysiologic Biomarkers in Rett Syndrome
An observational study of Rett Syndrome and RTT, run by Children's Hospital of Philadelphia at 6 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 1 year to 18 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Rett Syndrome, RTT, Rett Syndrome, Atypical
- What is being tested?
- EEG and Auditory and Visual Evoked Potentials (AEP and VEP) and Clinical assessment
- How many people
- 222 participants
- Where
- 6 sitesUnited States
- Study dates
- 11 Oct 2023to 31 Mar 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- Women only
- Healthy volunteers accepted
- Child, Adult
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).
Who may be able to join
- 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).
Who cannot join
- Rett and Likely Rett Groups:
- Presence of a duplication in MECP2 or any other identified pathogenic variant in another gene with a neurodevelopmental phenotype.
- 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.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
United States6 sites, 6 recruiting
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
Timothy Benke, MD, PhD
- Recruiting
Boston Children's Hospital
Brookline, Massachusetts, 02445
April Levin, MD
David Lieberman, MD, PhD
- Recruiting
Texas Children's Hospital
Houston, Texas, 77030
Bernhard Suter, MD
- Recruiting
Children's Hospital of Los Angeles
Los Angeles, California, 90027
Payal Kenia Gu, MD
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Nicole Thompson, 615-343-4586, Nicole.i.thompson@vumc.org
Jeffrey Neul, MD, PhD
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Holly Dubbs, MS, CGC, 215-590-1719, dubbsh@chop.edu
Eric Marsh, MD, PhD
About this study
Official title: Characterization of Translatable Neurophysiological Biomarkers to Enhance Therapeutic Development in Rett Syndrome
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.
Read the 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.
- Conditions
- Rett Syndrome, RTT, Rett Syndrome, Atypical
- Being tested
- EEG and Auditory and Visual Evoked Potentials (AEP and VEP), Clinical assessment
- Keywords
- Biomarker, EEG, Evoked Potentials, MECP2
- Medical subject headings
- Rett Syndrome, Rett Syndrome, Atypical
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
Clinical assessmentOther
Established clinical measures for RTT will be collected for RTT participants
| Study group | Role | What they receive |
|---|---|---|
| RTT Females | Females with Rett Syndrome Receives: Other: EEG and Auditory and Visual Evoked Potentials (AEP and VEP); Other: Clinical assessment | |
| Controls | Females with typical development Receives: Other: EEG and Auditory and Visual Evoked Potentials (AEP and VEP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 years
Auditory Evoked Potential (AEP) amplitude
Amplitude of P1, P2 and N1 peaks (uV)
Measured: 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.
Measured: 5 years
Visual Evoked Potential (VEP) amplitude
N1-P1 amplitude at Oz and other occipital electrodes will be calculated.
Measured: 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.
Measured: 5 years
Secondary outcomes (2)
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.
Measured: 5 years
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.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2023
- Study start11 Oct 2023
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Rett SyndromeStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 222 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Vanderbilt University Medical Center
- Responsible party
- Sponsor
- Investigators
- Eric Marsh, MD, PhD, Principal investigator, Children's Hospital of PhiladelphiaJeffrey Neul, MD, PhD, Principal investigator, Vanderbilt University Medical Cener
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05932589
- Sponsor's protocol ID
- 22-020633
- Other IDs
- 1R61NS130216-01, 4R33NS130216-04
- Status last verified
- Oct 2026
- First submitted
- 27 Jun 2023
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The investigators intend to submit deidentified patient data into the National Database for Autism Research (NDAR) and database of Genotypes and Phenotypes (dbGaP). Study protocols and data analysis methods will be shared through future publications.
Publications
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.
PubMed 32547374Saby 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.
PubMed 33480039LeBlanc 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.
PubMed 26332183
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of Translatable Neurophysiological Biomarkers to Enhance Therapeutic Development in Rett Syndrome
- ClinicalTrials.gov ID
- NCT05932589
- Acronym / sponsor ID
- 22-020633
- Conditions
- Rett Syndrome, RTT, Rett Syndrome, Atypical
- Keywords
- Biomarker, EEG, Evoked Potentials, MECP2
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 222 participants (estimated)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Vanderbilt University Medical Center
- Study start
- 11 Oct 2023 (actual)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 Mar 2029 (estimated)
- First posted
- 6 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RTT Females | – | Other: EEG and Auditory and Visual Evoked Potentials (AEP and VEP), Other: Clinical assessmentFemales with Rett Syndrome |
| Controls | – | Other: EEG and Auditory and Visual Evoked Potentials (AEP and VEP)Females with typical development |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- 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).
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (7 listed)
- Presence of a duplication in MECP2 or any other identified pathogenic variant in another gene with a neurodevelopmental phenotype.
- Active medical conditions not typically found in RTT.
- Score below norms on the performance tests
- Have a known neurological disorder (excluding migraine)
- Being on neuroactive medications.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Other | Controls, RTT Females |
| Clinical assessmentEstablished clinical measures for RTT will be collected for RTT participants | Other | RTT Females |
Primary outcome
Auditory Evoked Potential (AEP) latency (ms)
Time frame: 5 years
Calculated N1, P1 latencies in Cz and other electrodes [posterior temporal region (T5/P3/T3) electrodes], will be used for analysis.
Auditory Evoked Potential (AEP) amplitude
Time frame: 5 years
Amplitude of P1, P2 and N1 peaks (uV)
Visual Evoked Potential (VEP) latencies (ms)
Time frame: 5 years
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.
Visual Evoked Potential (VEP) amplitude
Time frame: 5 years
N1-P1 amplitude at Oz and other occipital electrodes will be calculated.
EEG Analysis
Time frame: 5 years
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.
2 secondary outcomes
AEP spectral analysis, dipole determination and spatial distribution
Time frame: 5 years
VEP spectral analysis, dipole determination and spatial distribution
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Background: PubMed 32547374Saby 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.
- Background: PubMed 33480039Saby 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.
- Background: PubMed 26332183LeBlanc 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.
- Individual participant dataSharing planned: Yes. The investigators intend to submit deidentified patient data into the National Database for Autism Research (NDAR) and database of Genotypes and Phenotypes (dbGaP). Study protocols and data analysis methods will be shared through future publications.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Eric Marsh, MD, PhD principal investigator
Children's Hospital of Philadelphia
Jeffrey Neul, MD, PhD principal investigator
Vanderbilt University Medical Cener
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rett Syndrome and RTT, run by Children's Hospital of Philadelphia at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Holly Dubbs, MS, CGC (215-590-1719, dubbsh@chop.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Auditory Evoked Potential (AEP) latency (ms) (time frame: 5 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05932589, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.