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

NCT ID: NCT00990691

Last Updated: 2018-07-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-02-17

Study Completion Date

2017-08-21

Brief Summary

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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

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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

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Rett Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Administration of a high dose of desipramine

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Administration of a low dose of desipramine

Intervention Type DRUG

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

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

Group Type PLACEBO_COMPARATOR

Administration of a placebo

Intervention Type DRUG

Administration of a daily dose of placebo

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Administration of a placebo

Administration of a daily dose of placebo

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

4 Years

Maximum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Assistance Publique Hopitaux De Marseille

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Josette Mancini

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique Hopitaux De Marseille

Locations

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Assistance Publique - Hopitaux de Marseille

Marseille, , France

Site Status

Countries

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France

References

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Mancini J, Dubus JC, Jouve E, Roux JC, Franco P, Lagrue E, Castelnau P, Cances C, Chaix Y, Rougeot-Jung C, Cornu C, Desportes V, Vallee L, Bahi-Buisson N, Truillet R, Attolini L, Villard L, Blin O, Micallef J. Effect of desipramine on patients with breathing disorders in RETT syndrome. Ann Clin Transl Neurol. 2017 Dec 27;5(2):118-127. doi: 10.1002/acn3.468. eCollection 2018 Feb.

Reference Type DERIVED
PMID: 29468173 (View on PubMed)

Other Identifiers

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2007-006739-30

Identifier Type: -

Identifier Source: secondary_id

2007-37

Identifier Type: -

Identifier Source: org_study_id

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