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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 4
- 主要终点
- Clinical Global Impression (CGI) scale
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 0 Years 至 18 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Clinical Global Impression (CGI) scale
时间窗: 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)
Mutation in MECP2
时间窗: every year for four years
Number of different single variant
Neuroscope alterations
时间窗: 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.
Age at diagnosis
时间窗: every year for four years
Thoracic radiographic alterations
时间窗: every year for four years
Brain magnetic resonance imaging (MRI) alteration
时间窗: every year for four years
Bone densitometry alterations
时间窗: every year for four years
Lumbosacral spine radiographic alterations
时间窗: every year for four years
Electroencephalogram (EEG) alterations
时间窗: every year for four years
The Rett Syndrome Behavioural Questionnaire (RSBQ)
时间窗: 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)
次要结局
- Alterations of neurovisual functions(every year for four years)
- Possibility of applying alternative forms of communication to verbal communication(every year for four years)
研究者
Roberta Battini
Professor
IRCCS Fondazione Stella Maris