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

This study is currently recruiting participants. (see Contacts and Locations)
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
  Purpose

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.


Condition Intervention Phase
Rett Syndrome
Drug: Administration of a high dose of desipramine
Drug: Administration of a low dose of desipramine
Drug: Administration of a placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Pilot Study of the Effects of the Desipramine on the Neurovegetative Parameters of the Child With Rett Syndrome

Resource links provided by NLM:


Further study details as provided by Assistance Publique Hopitaux De Marseille:

Primary Outcome Measures:
  • To study the efficacy of the desipramine on the respiratory disturbations [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To study the safety of the desipramine in the studied population [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 36
Study Start Date: October 2008
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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.
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.
Placebo Comparator: Placebo
12 patients with Rett syndrome receiving a daily dose of placebo.
Drug: Administration of a placebo
Administration of a daily dose of placebo

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.

  Eligibility

Ages Eligible for Study:   4 Years to 18 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00990691

Contacts
Contact: Josette Mancini josette.mancini@ap-hm.fr

Locations
France
Assistance Publique - Hopitaux de Marseille Recruiting
Marseille, France
Contact: Josette Mancini       josette.mancini@ap-hm.fr   
Principal Investigator: Josette Mancini         
Sponsors and Collaborators
Assistance Publique Hopitaux De Marseille
Investigators
Principal Investigator: Josette Mancini Assistance Publique Hopitaux De Marseille
  More Information

No publications provided

Responsible Party: Assistance Publique Hopitaux De Marseille
ClinicalTrials.gov Identifier: NCT00990691     History of Changes
Other Study ID Numbers: 2007-37, 2007-006739-30
Study First Received: October 6, 2009
Last Updated: February 24, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Assistance Publique Hopitaux De Marseille:
Rett syndrome

Additional relevant MeSH terms:
Rett Syndrome
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Desipramine
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 20, 2014