Biomarkers in Rett Syndrome

NCT06346444 | Recruiting

• 1 other identifier: 2.780.113
• Study Type: observational
• Target: 100
• Locations: 2 countries
• Sites: 4

Brief 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. 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.

Conditions

Rett Syndrome

Outcome Measures

Primary Outcomes (10)

• Age at diagnosis

  every year for four years

• Mutation in MECP2

  Number of different single variant

  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.

  every year for four years

• Electroencephalogram (EEG) alterations

  every year for four years

• Brain magnetic resonance imaging (MRI) alteration

  every year for four years

• Bone densitometry alterations

  every year for four years

• Thoracic radiographic alterations

  every year for four years

• Lumbosacral spine radiographic alterations

  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)

  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)

  every year for four years

Secondary Outcomes (2)

• Alterations of neurovisual functions

  every year for four years

• Possibility of applying alternative forms of communication to verbal communication

  every year for four years

Interventions

Diagnostic test and behavioral OTHER

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-)

Eligibility Criteria

• Age: 0 Years - 18 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• IRCCS Fondazione Stella Maris: lead
• Meyer Children's Hospital IRCCS: collaborator
• Azienda USL Toscana Nord Ovest: collaborator
• University of Dublin, Trinity College: collaborator

Study Sites (4)

Trinity College Institute of Neuroscience, Lloyd Building, D2

Dublin, Ireland

RECRUITING

Ospedale Versilia Centro di Riferimento

Lido di Camaiore, Lucca, 55049, Italy

RECRUITING

IRCCS Fondazione Stella Maris

Calambrone, Pisa, 56128, Italy

RECRUITING

AOU Meyer

Florence, 50139, Italy

RECRUITING

MeSH Terms

Conditions

Rett Syndrome

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Central Study Contacts

Roberta Battini

CONTACT

050886282; rbattini@fsm.unipi.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 4 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 22, 2024
• First Posted: April 4, 2024
• Study Start: August 3, 2020
• Primary Completion: February 20, 2024
• Study Completion: December 31, 2024
• Last Updated: April 4, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3); IE (1)