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

Public Assistance-Hospitals of Marseille (AP-HM)

Status and phase: Completed; Phase 2

Conditions: Rett Syndrome

Treatments: Drug: Administration of a high dose of desipramine; Drug: Administration of a low dose of desipramine; Drug: Administration of a placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT00990691

2007-37

2007-006739-30

Details and patient eligibility

About

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.

Full 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.

Enrollment: 36 patients

Sex: Female

Ages: 4 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Rett syndrome;
• Girls weighing less than 60 kg;
• Respiratory alteration;
• Diagnosis of Rett syndrome confirmed by MECP2 genotyping (Xq28).

Exclusion criteria

• Boys;
• Pregnancy and breath feeding;
• Case history of status epilepticus;
• Patient treated by IMAO or sultopride;
• Hepatic or renal failure.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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36 participants in 3 patient groups, including a placebo group

Desipramine high dose

Experimental group

Description:

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.

Treatment:

Drug: Administration of a high dose of desipramine

Desipramine low dose

Experimental group

Description:

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.

Treatment:

Drug: Administration of a low dose of desipramine

Placebo

Placebo Comparator group

Description:

12 patients with Rett syndrome receiving a daily dose of placebo.

Treatment:

Drug: Administration of a placebo