Rett SyndromeBIRSNCT06346444
Biomarkers in Rett Syndrome
An observational study of Rett Syndrome, run by IRCCS Fondazione Stella Maris at 4 sites in 2 countries.
Trial summary
Rett syndrome (RTT) is an X-linked genetic disorder that causes severe neurological development disorder. In its classic form, it seems to affect almost exclusively females with an incidence of up to one in 10,000 females. Read more about this study
- Who is it for?
- Ages 0 to 18 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Rett Syndrome
- What is being tested?
- Diagnostic test and behavioral
- How many people
- 100 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 3 Aug 2020to 31 Dec 2024
- How long will I take part?
- 4 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
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 0 to 18 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Study population: The sample size has been estimated according to the syndrome's prevalence in the general population and based on the number of retrospective patient samples affected by Rett Syndrome and Reti-like Syndrome.
Who may be able to join
- All subjects aged between 0 and 18 years with Rett Syndrome, classic (mutation of the MECP2 gene) and Rett variants (CDKL5, FOXG1 mutations, and other MECP2 mutations), genetically confirmed:
- newly diagnosed
- previously diagnosed if possessing data recorded and stored in the enrollment centers' records;
- upon written informed consent from the parents.
- Siblings of the probands of any age who will undergo EEG registration will also be enrolled.
Who cannot join
- Patients with Rett Syndrome presenting a compromise in the general health status to such an extent that it makes it impossible to apply the clinical-instrumental evaluation and monitoring tools used for the study.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Italy3 sites, 3 recruiting
- Recruiting
IRCCS Fondazione Stella Maris
Calambrone, Pisa, 56128
Roberta Battini, 050886282, rbattini@fsm.unipi.it
- Recruiting
AOU Meyer
Florence, 50139
Viola Doccini, viola.doccini@meyer.it
- Recruiting
Ospedale Versilia Centro di Riferimento
Lido di Camaiore, Lucca, 55049
Ilaria Gemo, ilaria.gemo@uslnordovest.toscana.it
Ireland1 site, 1 recruiting
- Recruiting
Trinity College Institute of Neuroscience, Lloyd Building, D2
Dublin
Daniela Tropea, daniela.tropea@tcd.ie
About this study
Official title: BIRS (Biomarkers in Rett Syndrome): a Long-term Observational Multicenter Study of the Natural History of Rett Syndrome to Define New Clinical and Instrumental Biomarkers
Rett syndrome (RTT) is an X-linked genetic disorder that causes severe neurological development disorder. In its classic form, it seems to affect almost exclusively females with an incidence of up to one in 10,000 females. Patients affected by Rett Syndrome can present a wide range of symptoms, in different combinations and of varying intensity, such as slowed growth of head circumference, abnormalities in walking and balance, loss of functional use of the hands often replaced by repetitive and stereotyped hand movements like "hand washing", loss of communicative-relational skills including expressive language, epilepsy, breathing abnormalities, and osteo-muscular alterations. In light of the growing potential of clinical therapies, identification and early diagnosis are considered essential. Many disease modification strategies have been achieved through translational research studies and clinical trials that have allowed the recognition of the most effective therapeutic and clinical interventions to date.
This study arises from the need to advance in the understanding of the pathogenesis of RTT through a multicentric collaboration in order to (a) identify early biomarkers of RTT (b) delve into the alterations of interconnectivity, crucial for understanding the loss of motor functions and language through systematic collection of anamnestic, genetic, and clinical-instrumental data. The aim is to provide a valuable contribution to the study of the clinical phenotype of Rett and the identification of early interventions.
Read the detailed description
The study aims to collect and analyze clinical-instrumental data from patients affected by Rett Syndrome through a prolonged monitoring program aimed at identifying disease biomarkers.
The study is a prospective observational type, with multicentric enrollment (IRCCS Stella Maris, AOU Meyer, Versilia Hospital Regional Reference Center for Rett Syndrome-USL Toscana Nord-Ovest), non-profit. New diagnosis patients and patients already included in the databases of each center will be enrolled. The cohort observational study will be completed, where possible, by a case-control study that involves the enrollment of siblings of the proband included in the study cohort.
Data regarding the registration of brain electrical activity through EEG of both the cohort and the patients' siblings, and acquisitions through Eye Tracker of the patients only, will be analyzed by Dr. Daniela Tropea's study group at Trinity College Dublin (Genetic Neuropsychiatry and Neuroscience Institute).
The study is expected to start immediately after the approval of the protocol by this Ethics Committee.
The study is expected to last four years. The study involves the enrollment of every case of Rett syndrome in the developmental age attending one of the Italian centers and an annual follow-up with clinical and instrumental controls provided by a dedicated path.
Sample Size The sample size has been estimated according to the syndrome's prevalence in the general population and based on the number of retrospective patient samples affected by Rett Syndrome.
The study plans to enroll approximately 100 patients consecutively, according to a pre-established schedule that includes observations and evaluations provided by the protocol.
FOLLOW-UP PROCEDURE The follow-up of each patient will be carried out annually through clinical monitoring and instrumental application of what is listed in the primary endpoint except for the brain MRI, whose repetition if necessary will be agreed upon based on the evolution of the clinical picture.
DEFINITION OF STUDY CONCLUSION The end of the monitoring of patients is expected upon reaching the age of 18 years.
DATA MANAGEMENT For each recruited patient, after deliberation through informed consent, data contained within the clinical record will be collected. At recruitment, data related to diagnosis, gestational age at birth, auxological parameters at birth, Apgar score, main clinical anamnestic data related to the perinatal period, and outcome of neuroimaging assessments carried out (for example, brain MRI, transfontanellar cerebral ultrasound) will be acquired and recorded in a specific database.
To protect privacy, each patient will be assigned a numeric code, therefore the database will not contain any demographic data, and access will be protected by a password and limited to personnel involved in the study only. The database will be progressively implemented with the outcomes of the assessments, acquired systematically, according to the correspondence code of the individual subject. The EEG video recording data will be accessible from the clinical documentation and coded systematically. The EEG data and the acquisitions through Eye Tracker obtained in the Italian enrollment centers will be analyzed at Trinity College Dublin in an anonymous manner through identification by numeric code and only after signed consent from the parents.
DATA CONSERVATION The data managers and the measures of anonymization will be the responsibility of the main experimenters of the study. All data will be stored in secure places and on password-protected files, at the patient's home institute.
ETHICAL CONSIDERATIONS The study conforms to the ethical principles recognized for clinical experimentation, to the principles of good clinical practice.
The protocol has been submitted for approval to the ethical committee and/or competent authority.
ACQUISITION OF INFORMED CONSENT AND DATA PROCESSING At the time of the direct interview with the families, a detailed explanation will be provided orally and a written informative note (which will remain with the parents). The importance of the study and the data used for the purposes of our study will also be explained, specifying the request for release for the compilation of the database, however under an identification code.
The paper documents related to informed consent will be handed over to the family so that they can be read and understood in their entirety and retrieved following a subsequent interview in which the parents can ask clarifying questions and definitively confirm their consent to the study.
- Conditions
- Rett Syndrome
- Being tested
- Diagnostic test and behavioral
- Medical subject headings
- Rett Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diagnostic test and behavioralOther
Questionnaires (CGI, RSBQ) and Outcome measurements (Neuroscope, EEG, Brain MRI, Bone densitometry, X-ray of thoracic and lumbosacral spine Blood biomarkers-RNA, proteins, other metabolites-)
What is being measured
The primary outcome is the main question the study is designed to answer.
Age at diagnosis
Measured: every year for four years
Mutation in MECP2
Number of different single variant
Measured: every year for four years
Neuroscope alterations
NeuroScope is an advanced viewer for neurophysiological and behavioral data: it can display local field potentials (LFPs), neuronal spikes and behavioral events.
Measured: every year for four years
Electroencephalogram (EEG) alterations
Measured: every year for four years
Brain magnetic resonance imaging (MRI) alteration
Measured: every year for four years
Bone densitometry alterations
Measured: every year for four years
Thoracic radiographic alterations
Measured: every year for four years
Lumbosacral spine radiographic alterations
Measured: every year for four years
Clinical Global Impression (CGI) scale
The CGI scale has two components-the CGI-Severity, which rates illness severity of ill (Score from 1 to 7, where 1 is normal and 7 severely ill) , and the CGI-Improvement, which rates change from the initiation (baseline) of observation (Score from 1 to 7, where 1 is very much improved since the initiation of observation and 7 is very much worse since the initiation of observation)
Measured: every year for four years
The Rett Syndrome Behavioural Questionnaire (RSBQ)
The Rett Syndrome Behaviour Questionnaire (RSBQ) assesses the severity of neurobehavioral problems from the perspective of the caregiver. The RSBQ consists of 45 items of which 38 items are grouped into 8 domains/subscales that reflect the core features (General Mood; Breathing Problems; Hand Behaviors; Repetitive Face Movements; Body Rocking and Expressionless Face; Nighttime Behaviors; Fear/Anxiety; and Walking/Standing) and 7 items are grouped into a subscales classed as "uncategorized" but contribute to the overall total score. Each item is rated on a Likert scale as 0 (behavior "not true"), 1 (behavior "somewhat or sometimes true") or 2 (behavior "often true"), with the total score ranging from 0 to 90 (higher scores indicate increased severity)
Measured: every year for four years
Secondary outcomes (2)
Alterations of neurovisual functions
Measured: every year for four years
Possibility of applying alternative forms of communication to verbal communication
Possibility of applying alternative forms of communication to verbal communication (in patients presenting with the absence of expressive language) through the application of the EYE TRACKER device (Tobii Dyanvox) that uses near-infrared lighting in combination with high-definition cameras to project light into the eye and record the direction reflected by the cornea
Measured: every year for four years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2024
- Study start3 Aug 2020
- Primary completion20 Feb 2024
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rett SyndromeStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
- Target duration
- 4 Years
Sponsor and investigators
- Lead sponsor
- IRCCS Fondazione Stella Maris
- Sponsor type
- University, hospital or other
- Collaborators
- Meyer Children's Hospital IRCCS, Azienda USL Toscana Nord Ovest, University of Dublin, Trinity College
- Responsible party
- Principal investigator, Roberta Battini, IRCCS Fondazione Stella Maris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06346444
- Sponsor's protocol ID
- 2.780.113
- Acronym
- BIRS
- Status last verified
- Mar 2024
- First submitted
- 22 Feb 2024
- Last updated
- 4 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BIRS (Biomarkers in Rett Syndrome): a Long-term Observational Multicenter Study of the Natural History of Rett Syndrome to Define New Clinical and Instrumental Biomarkers
- ClinicalTrials.gov ID
- NCT06346444
- Acronym / sponsor ID
- BIRS / 2.780.113
- Conditions
- Rett Syndrome
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- IRCCS Fondazione Stella MarisUniversity, hospital or other
- Collaborators
- Meyer Children's Hospital IRCCS, Azienda USL Toscana Nord Ovest, University of Dublin, Trinity College
- Study start
- 3 Aug 2020 (actual)
- Primary completion
- 20 Feb 2024 (actual)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 4 Apr 2024 (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.
Rett syndrome (RTT) is an X-linked genetic disorder that causes severe neurological development disorder. In its classic form, it seems to affect almost exclusively females with an incidence of up to one in 10,000 females. Patients affected by Rett Syndrome can present a wide range of symptoms, in different combinations and of varying intensity, such as slowed growth of head circumference, abnormalities in walking and balance, loss of functional use of the hands often replaced by repetitive and stereotyped hand movements like "hand washing", loss of communicative-relational skills including expressive language, epilepsy, breathing abnormalities, and osteo-muscular alterations. In light of the growing potential of clinical therapies, identification and early diagnosis are considered essential. Many disease modification strategies have been achieved through translational research studies and clinical trials that have allowed the recognition of the most effective therapeutic and clinical interventions to date.
This study arises from the need to advance in the understanding of the pathogenesis of RTT through a multicentric collaboration in order to (a) identify early biomarkers of RTT (b) delve into the alterations of interconnectivity, crucial for understanding the loss of motor functions and language through systematic collection of anamnestic, genetic, and clinical-instrumental data. The aim is to provide a valuable contribution to the study of the clinical phenotype of Rett and the identification of early interventions.
Detailed description
The study aims to collect and analyze clinical-instrumental data from patients affected by Rett Syndrome through a prolonged monitoring program aimed at identifying disease biomarkers.
The study is a prospective observational type, with multicentric enrollment (IRCCS Stella Maris, AOU Meyer, Versilia Hospital Regional Reference Center for Rett Syndrome-USL Toscana Nord-Ovest), non-profit. New diagnosis patients and patients already included in the databases of each center will be enrolled. The cohort observational study will be completed, where possible, by a case-control study that involves the enrollment of siblings of the proband included in the study cohort.
Data regarding the registration of brain electrical activity through EEG of both the cohort and the patients' siblings, and acquisitions through Eye Tracker of the patients only, will be analyzed by Dr. Daniela Tropea's study group at Trinity College Dublin (Genetic Neuropsychiatry and Neuroscience Institute).
The study is expected to start immediately after the approval of the protocol by this Ethics Committee.
The study is expected to last four years. The study involves the enrollment of every case of Rett syndrome in the developmental age attending one of the Italian centers and an annual follow-up with clinical and instrumental controls provided by a dedicated path.
Sample Size The sample size has been estimated according to the syndrome's prevalence in the general population and based on the number of retrospective patient samples affected by Rett Syndrome.
The study plans to enroll approximately 100 patients consecutively, according to a pre-established schedule that includes observations and evaluations provided by the protocol.
FOLLOW-UP PROCEDURE The follow-up of each patient will be carried out annually through clinical monitoring and instrumental application of what is listed in the primary endpoint except for the brain MRI, whose repetition if necessary will be agreed upon based on the evolution of the clinical picture.
DEFINITION OF STUDY CONCLUSION The end of the monitoring of patients is expected upon reaching the age of 18 years.
DATA MANAGEMENT For each recruited patient, after deliberation through informed consent, data contained within the clinical record will be collected. At recruitment, data related to diagnosis, gestational age at birth, auxological parameters at birth, Apgar score, main clinical anamnestic data related to the perinatal period, and outcome of neuroimaging assessments carried out (for example, brain MRI, transfontanellar cerebral ultrasound) will be acquired and recorded in a specific database.
To protect privacy, each patient will be assigned a numeric code, therefore the database will not contain any demographic data, and access will be protected by a password and limited to personnel involved in the study only. The database will be progressively implemented with the outcomes of the assessments, acquired systematically, according to the correspondence code of the individual subject. The EEG video recording data will be accessible from the clinical documentation and coded systematically. The EEG data and the acquisitions through Eye Tracker obtained in the Italian enrollment centers will be analyzed at Trinity College Dublin in an anonymous manner through identification by numeric code and only after signed consent from the parents.
DATA CONSERVATION The data managers and the measures of anonymization will be the responsibility of the main experimenters of the study. All data will be stored in secure places and on password-protected files, at the patient's home institute.
ETHICAL CONSIDERATIONS The study conforms to the ethical principles recognized for clinical experimentation, to the principles of good clinical practice.
The protocol has been submitted for approval to the ethical committee and/or competent authority.
ACQUISITION OF INFORMED CONSENT AND DATA PROCESSING At the time of the direct interview with the families, a detailed explanation will be provided orally and a written informative note (which will remain with the parents). The importance of the study and the data used for the purposes of our study will also be explained, specifying the request for release for the compilation of the database, however under an identification code.
The paper documents related to informed consent will be handed over to the family so that they can be read and understood in their entirety and retrieved following a subsequent interview in which the parents can ask clarifying questions and definitively confirm their consent to the study.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 4 Years
Who may qualify
- Ages
- 0 to 18 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- The sample size has been estimated according to the syndrome's prevalence in the general population and based on the number of retrospective patient samples affected by Rett Syndrome and Reti-like Syndrome.
Key inclusion criteria (5 listed)
- All subjects aged between 0 and 18 years with Rett Syndrome, classic (mutation of the MECP2 gene) and Rett variants (CDKL5, FOXG1 mutations, and other MECP2 mutations), genetically confirmed:
- Siblings of the probands of any age who will undergo EEG registration will also be enrolled.
Key exclusion criteria (1 listed)
- Patients with Rett Syndrome presenting a compromise in the general health status to such an extent that it makes it impossible to apply the clinical-instrumental evaluation and monitoring tools used for the study.
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 |
|---|---|---|
| Diagnostic test and behavioralQuestionnaires (CGI, RSBQ) and Outcome measurements (Neuroscope, EEG, Brain MRI, Bone densitometry, X-ray of thoracic and lumbosacral spine Blood biomarkers-RNA, proteins, other metabolites-) | Other | – |
Primary outcome
Age at diagnosis
Time frame: every year for four years
Mutation in MECP2
Time frame: every year for four years
Number of different single variant
Neuroscope alterations
Time frame: every year for four years
NeuroScope is an advanced viewer for neurophysiological and behavioral data: it can display local field potentials (LFPs), neuronal spikes and behavioral events.
Electroencephalogram (EEG) alterations
Time frame: every year for four years
Brain magnetic resonance imaging (MRI) alteration
Time frame: every year for four years
Bone densitometry alterations
Time frame: every year for four years
Thoracic radiographic alterations
Time frame: every year for four years
Lumbosacral spine radiographic alterations
Time frame: every year for four years
Clinical Global Impression (CGI) scale
Time frame: every year for four years
The CGI scale has two components-the CGI-Severity, which rates illness severity of ill (Score from 1 to 7, where 1 is normal and 7 severely ill) , and the CGI-Improvement, which rates change from the initiation (baseline) of observation (Score from 1 to 7, where 1 is very much improved since the initiation of observation and 7 is very much worse since the initiation of observation)
The Rett Syndrome Behavioural Questionnaire (RSBQ)
Time frame: every year for four years
The Rett Syndrome Behaviour Questionnaire (RSBQ) assesses the severity of neurobehavioral problems from the perspective of the caregiver. The RSBQ consists of 45 items of which 38 items are grouped into 8 domains/subscales that reflect the core features (General Mood; Breathing Problems; Hand Behaviors; Repetitive Face Movements; Body Rocking and Expressionless Face; Nighttime Behaviors; Fear/Anxiety; and Walking/Standing) and 7 items are grouped into a subscales classed as "uncategorized" but contribute to the overall total score. Each item is rated on a Likert scale as 0 (behavior "not true"), 1 (behavior "somewhat or sometimes true") or 2 (behavior "often true"), with the total score ranging from 0 to 90 (higher scores indicate increased severity)
2 secondary outcomes
Alterations of neurovisual functions
Time frame: every year for four years
Possibility of applying alternative forms of communication to verbal communication
Time frame: every year for four years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2024.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rett Syndrome, run by IRCCS Fondazione Stella Maris at 4 sites in 2 countries.
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 5 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 4 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy, Ireland. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Roberta Battini (050886282, rbattini@fsm.unipi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Age at diagnosis (time frame: every year for four years). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Apr 2024.