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

Brief Title

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

Official Title

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

Brief 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.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

To study the efficacy of the desipramine on the respiratory disturbations

Secondary Outcome

 To study the safety of the desipramine in the studied population

Condition

Rett Syndrome

Intervention

Administration of a high dose of desipramine

Study Arms / Comparison Groups

 Desipramine high dose

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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

36

Start Date

February 17, 2009

Completion Date

August 21, 2017

Primary Completion Date

August 11, 2014

Eligibility Criteria

        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.
      

Gender

Female

Ages

4 Years - 18 Years

Accepts Healthy Volunteers

No

Contacts

Josette Mancini, , 

Location Countries

France

Location Countries

France

NCT ID

NCT00990691

Organization ID

2007-37

Secondary IDs

2007-006739-30

Responsible Party

Sponsor

Study Sponsor

Assistance Publique Hopitaux De Marseille

Study Sponsor

Josette Mancini, Principal Investigator, Assistance Publique Hopitaux De Marseille

Verification Date

July 2018