Study of Metabolic Modifications in Children With Noonan Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Insulin sensitivity determined from the calculation of the Quantitative insulin sensitivity check index (QUICKI).
研究概览
简要总结
Noonan syndrome (NS) is a rare genetic disease (incidence 1/2500 live births) characterized by the association of craniofacial manifestations, cardiopathies, short stature, and tumor predisposition. The genetic causes of Noonan Syndrome are mutations of genes involved in the Ras/Mitogen-Activated Protein Kinases (MAPK) pathway, mainly the gene encoding the tyrosine phosphatase Shp2 (50% of patients).Shp2 appears to be involved in many facets of energy metabolism control (glucose homeostasis, adipose tissue function…), through mechanisms that are poorly understood. Several metabolic anomalies (reduced adiposity, improved glucose tolerance) have been recently identified in an original mouse model carrying Shp2 mutation. Moreover, recent clinical survey has shown that adult Noonan Syndrome patients are protected from developping overweight and obesity when compared to the general population. However, the metabolic status associated with Noonan Syndrome condition has not been explored to date.
详细描述
Differential hormone sensitivity is associated with Noonan Syndrome and participates in the development of some symptoms. The investigators have demonstrated that MAPK upregulation in Noonan Syndrome is responsible for partial growth hormone (GH) insensitivity, and subsequent growth retardation.
Clinical traits evocative of energy metabolism dysfunctions have been recently reported in Noonan Syndrome patients, although the origins and consequences of these metabolic changes have not been documented to date. The aim of this study is to explore the metabolic status of children with Noonan Syndrome.
Children with Noonan Syndrome will be compared with age- and sex-matched healthy children. The investigators hypothesize than Noonan Syndrome children have an increased insulin sensitivity compared to GHD children.
Study parameters will be collected including: clinical measurements (height, weight, body mass index, waist circumference, and blood pressure), glucose and insulin levels at baseline and after an oral glucose tolerance test (OGTT), body composition measured by dual-energy x-ray absorptiometry (DXA).
The study will include only one visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 7 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Noonan syndrome genetically confirmed
- •Informed consent obtained from children and parents
排除标准
- •Chronic disease associated with variation of insulin sensitivity: body mass
- •Treatment associated with variation of insulin sensitivity: corticoid treatment > 5 days preceding the study inclusion
- •Tumoral disease (leukemia) in treatment
研究组 & 干预措施
Noonan Syndrome Children
Children with Noonan Syndrome will be compared with age- and sex-matched healthy children. We hypothesize than Noonan Syndrome children have an increased insulin sensitivity compared to GHD children.
Study parameters will be collected including: clinical measurements (height, weight, body mass index, waist circumference, and blood pressure), glucose and insulin levels at baseline and after an oral glucose tolerance test (OGTT), body composition measured by dual-energy x-ray absorptiometry (DXA).
干预措施: Oral Glucose tolerance test (Other)
结局指标
主要结局
Insulin sensitivity determined from the calculation of the Quantitative insulin sensitivity check index (QUICKI).
时间窗: T0 on an empty stomach
Measured at the patient's arrival (TO) from the blood levels of glucose and fasting insulin
次要结局
- Waist circumference(T0)
- Insulin sensitivity determined with HOMA index(T30, T60, T90 and T120 minutes after oral glucose tolerance test)
- Body mass index(T0)
- Blood pressure(T0)
- Blood level of ghrelin(T0 on an empty stomach)
- Blood level of hemoglobin A1c and ghrelin(T0 on an empty stomach)
- Body composition as fat mass and muscle mass measured by dual-energy x-ray absorptiometry (DXA)(T0)
- Blood level of leptin(T0 on an empty stomach)