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

This study is currently recruiting participants.
Verified February 2014 by Assistance Publique Hopitaux De Marseille
Sponsor:
Information provided by (Responsible Party):
Assistance Publique Hopitaux De Marseille
ClinicalTrials.gov Identifier:
NCT00990691
First received: October 6, 2009
Last updated: February 24, 2014
Last verified: February 2014

October 6, 2009
February 24, 2014
October 2008
September 2014   (final data collection date for primary outcome measure)
To study the efficacy of the desipramine on the respiratory disturbations [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00990691 on ClinicalTrials.gov Archive Site
To study the safety of the desipramine in the studied population [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Pilot Study of the Effects of the Desipramine on the Neurovegetative Parameters of the Child With Rett Syndrome
Pilot Study of the Effects of the Desipramine on the Neurovegetative Parameters of the Child With Rett Syndrome

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Rett Syndrome
  • 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
  • Experimental: 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.
    Intervention: Drug: Administration of a high dose of desipramine
  • Experimental: 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.
    Intervention: Drug: Administration of a low dose of desipramine
  • Placebo Comparator: Placebo
    12 patients with Rett syndrome receiving a daily dose of placebo.
    Intervention: Drug: Administration of a placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
36
Not Provided
September 2014   (final data collection date for primary outcome measure)

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.
Female
4 Years to 18 Years
No
Contact: Josette Mancini josette.mancini@ap-hm.fr
France
 
NCT00990691
2007-37, 2007-006739-30
No
Assistance Publique Hopitaux De Marseille
Assistance Publique Hopitaux De Marseille
Not Provided
Principal Investigator: Josette Mancini Assistance Publique Hopitaux De Marseille
Assistance Publique Hopitaux De Marseille
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP