NCT00990691

Pilot Study of the Effects of the Desipramine on the Neurovegetative Parameters of the Child With Rett Syndrome

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: Assistance Publique Hopitaux De Marseille · Academic / Other
• Sex: Female
• Age: 4 Years – 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Rett Syndrome

Interventions

Type	Name	Description
DRUG	Administration of a high dose of desipramine	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.
DRUG	Administration of a low dose of desipramine	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.
DRUG	Administration of a placebo	Administration of a daily dose of placebo

Timeline

• Start date: 2009-02-17
• Primary completion: 2014-08-11
• Completion: 2017-08-21
• First posted: 2009-10-07
• Last updated: 2018-07-26

Locations

1 site across 1 country: France