Cornelia De Lange Syndrome: Assessing Positive Effects of Lithium Treatment
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Behaviour
研究概览
简要总结
The study "Cornelia de Lange Syndrome: assessing positive effects of Lithium treatment - CLoSER" aims to evaluate the effectiveness on behavioral modifications of lithium carbonate therapy in patients with Cornelia de Lange syndrome (CdLS).
CdLS is a rare genetic disease caused by autosomal mutations dominant or X-linked. The prevalence of CdLS is estimated to be between 1:10,000-30,000 newborns, but it is probably underestimated because the most cases mild ones may go undiagnosed. This syndrome is characterized by slow growth before and after birth with intellectual disability and short stature, from major malformations such as facial anomalies, neurological disorders, gastrointestinal and musculoskeletal malformations. To date, for these patients only targeted medical and surgical therapeutic interventions are recommended for improving the quality of life. No drug therapy is validated for the cognitive/behavioral disorders. It has been shown that lihium-dependent activation of the WNT pathway is able to recover the Abnormal phenotype in many CdLS models. Lithium is already widely used in psychiatry and has a long history of clinical efficacy.
Recently some studies are evaluating the effect of lithium in patients with characteristics common to CdLS showing promising results . This trial intends to transfer the preliminary data obtained from in vitro and in vivo studies on patients with CdLS.
Given the currently untreatable nature of the syndrome, this treatment could represent a possible therapeutic strategy aimed at improving the behavioral and intellectual disabilities typical of CdLS.
详细描述
Research Objectives This study aims to evaluate the effectiveness of lithium carbonate therapy on behavioral changes in patients with Cornelia de Lange syndrome (CdLS). This is a multicenter and non-commercial pilot clinical study.
The specific objectives are the following:
PRIMARY OUTCOME - Improvement in the following parameters:
• Behavior assessed by Aberrant Behavior Checklist (ABC scale1), which measures psychiatric symptoms and behavioral disorders also in patients with intellectual disability;
SECONDARY OUTCOMES - Improvement in the following parameters:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 4 years
- •Body weight within the normal range in the reference range for CdLS, based on age and height
- •Diagnosis of CdLS based on consensus clinical criteria and a confirmed mutation in the NIPBL gene
- •Stable drug regimen for 4 weeks prior to starting the study
- •Written consent signed by parent/legal guardian/representative prior to the screening visit
- •Ability to take the study drug provided in capsules or drops (for younger patients and those with swallowing difficulties) or combined with food/drinks
- •Caregiver must be able to understand the instructions and participate knowingly in the study
排除标准
- •The patient is participating in another clinical trial
- •QT interval prolongation, thyroid dysfunction, renal insufficiency, hepatic insufficiency, leukopenia, or other currently clinically significant medical disorders (as determined by the investigator), other than those directly related to CdLS
- •QTcF interval on ECG greater than 450 msec
- •Severe diabetes mellitus or inherited metabolic disorder
研究组 & 干预措施
CdLS patients with NIPBL mutation
Patients will be given 10mg/Kg twice a day, 150mg or 300mg Lithium Carbonate
干预措施: Lithium Carbonate Capsule (Drug)
结局指标
主要结局
Behaviour
时间窗: Change at 12 months from baseline of supplementation
Behaviour assessed through the Aberrant Behaviour checklist (ABC1 scale) which mesaure psychiatric symptomatology and behavioral disorders also in patients with intellectual disabilities. minimum total score: 0; maximum total score:174. Higher scores mean worse outcome
次要结局
- Communication(Change at 12 months from baseline of supplementation)
- Behaviour(Change at 12 months from baseline of supplementation)
- Sleep disturbances(Change at 12 months from baseline of supplementation)
- Clinical features(Change at 12 months from baseline of supplementation)
- Cognitive Performance(Change at 12 months from baseline of supplementation)
- Adaptive functioning in the different areas(Change at 12 months from baseline of supplementation)
- Quality of life(Change at 12 months from baseline of supplementation)
研究者
Aglaia Vignoli
Professor
University of Milan