Pilot Study of the Effects of the Desipramine on the Neurovegetative Parameters of the Child With Rett Syndrome
Condition: Rett Syndrome
MeSH terms: Rett Syndrome; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Administration of a high dose of desipramine; Administration of a low dose of desipramine; Administration of a placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Administration of a daily dose of desipramine correlated with the patient's 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.; Administration of a daily dose of desipramine correlated with the patient's 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.; Administration of a daily dose of placebo
Intervention MeSH terms: Desipramine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Rett syndrome