Pilot Study of the Effects of the Desipramine on the Neurovegetative Parameters of the Child With Rett Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- To study the efficacy of the desipramine on the respiratory disturbations
研究概览
简要总结
Rett syndrome is a neurodevelopmental disorder characterized by cognitive impairment, communication dysfunction, stereotypic movement disorder, and growth failure. Rett syndrome is caused by mutations in the Methyl CpG-Binding Protein-2 (MECP2) gene and has no treatment.
A mouse experimental model of Rett syndrome created by genetic invalidation of the MECP2 gene is available. It had been then observed that adult MECP2-deficient mice show respiratory alterations and found that endogenous noradrenaline helps to maintain a normal respiratory rhythm. Desipramine, a selective inhibitor of norepinephrine reuptake, seems to be efficient to reduce the respiratory alteration occuring in MECP2-deficient mice (Insem patent 2005, Villard and Roux 2006).
The aim of the study is to evaluate these obtained results in MECP2-deficient mice on patients with Rett syndrome.
详细描述
Rett syndrome is a neurodevelopmental disorder characterized by cognitive impairment, communication dysfunction, stereotypic movement disorder, and growth failure. The diagnosis of Rett syndrome is based on consensus clinical criteria. Rett syndrome is caused by mutations in the Methyl CpG-Binding Protein-2 (MECP2) gene and has no treatment.
Only a few improved cases have been reported concerning buspirone (Andaku, 2005, 1 patient), topiramate (Goyal, 2004, 8 patients), diazepam (Kurihara, 2001, 1 patient) and carnitin (Plochl, 2004, 1 patient).
Only one randomized study versus placebo has been published about a treatment by naltrexone including 25 patients. A light improvement of respiratory parameters was then observed with a deterioration of the cognitive function (Percy, 2004).
A mouse experimental model of Rett syndrome created by genetic invalidation of the MECP2 gene is available. It had been then observed that adult MECP2-deficient mice show respiratory alterations and found that endogenous noradrenaline helps to maintain a normal respiratory rhythm. Desipramine, a selective inhibitor of norepinephrine reuptake, seems to be efficient to reduce the respiratory alteration occuring in MECP2-deficient mice (Insem patent 2005, Villard and Roux 2006).
The aim of the study is to evaluate these obtained results in MECP2-deficient mice on patients with Rett syndrome.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 4 Years 至 18 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Rett syndrome;
- •Girls weighing less than 60 kg;
- •Respiratory alteration;
- •Diagnosis of Rett syndrome confirmed by MECP2 genotyping (Xq28).
排除标准
- •Pregnancy and breath feeding;
- •Case history of status epilepticus;
- •Patient treated by IMAO or sultopride;
- •Hepatic or renal failure.
研究组 & 干预措施
Desipramine high dose
12 patients with Rett syndrome receiving a daily dose of desipramine correlated with the weight :
- From 15 to 25 kg : 50 mg ;
- From 26 to 35 kg : 75 mg ;
- From 36 to 45 kg : 100 mg ;
- > 46 kg : 150 mg.
干预措施: Administration of a high dose of desipramine (Drug)
Desipramine low dose
12 patients with Rett syndrome receiving a daily dose of desipramine correlated with the weight :
- From 15 to 25 kg : 25 mg ;
- From 26 to 35 kg : 50 mg ;
- From 36 to 45 kg : 75 mg ;
- > 46 kg : 100 mg.
干预措施: Administration of a low dose of desipramine (Drug)
Placebo
12 patients with Rett syndrome receiving a daily dose of placebo.
干预措施: Administration of a placebo (Drug)
结局指标
主要结局
To study the efficacy of the desipramine on the respiratory disturbations
时间窗: 2 years
次要结局
- To study the safety of the desipramine in the studied population(2 years)