Effect of desipramine on patients with ...
Document type :
Article dans une revue scientifique: Article original
DOI :
PMID :
Permalink :
Title :
Effect of desipramine on patients with breathing disorders in rett syndrome
Author(s) :
Mancini, Josette [Auteur]
Dubus, Jean-Christophe [Auteur]
Jouve, Elisabeth [Auteur]
Roux, Jean-Christophe [Auteur]
Franco, Patricia [Auteur]
Lagrue, Emmanuelle [Auteur]
Castelnau, Pierre [Auteur]
Cances, Claude [Auteur]
Chaix, Yves [Auteur]
Rougeot-Jung, Christelle [Auteur]
Cornu, Catherine [Auteur]
Desportes, Vincent [Auteur]
Vallee, Louis [Auteur]
Bahi-Buisson, Nadia [Auteur]
Truillet, Romain [Auteur]
Attolini, Laurence [Auteur]
Villard, Laurent [Auteur]
Blin, Olivier [Auteur]
Micallef, Joelle [Auteur]
Dubus, Jean-Christophe [Auteur]
Jouve, Elisabeth [Auteur]
Roux, Jean-Christophe [Auteur]
Franco, Patricia [Auteur]
Lagrue, Emmanuelle [Auteur]
Castelnau, Pierre [Auteur]
Cances, Claude [Auteur]
Chaix, Yves [Auteur]
Rougeot-Jung, Christelle [Auteur]
Cornu, Catherine [Auteur]
Desportes, Vincent [Auteur]
Vallee, Louis [Auteur]
Bahi-Buisson, Nadia [Auteur]
Truillet, Romain [Auteur]
Attolini, Laurence [Auteur]
Villard, Laurent [Auteur]
Blin, Olivier [Auteur]
Micallef, Joelle [Auteur]
Journal title :
Annals of clinical and translational neurology
Abbreviated title :
Ann. Clin. Transl. Neurol.
Volume number :
5
Pages :
118-127
Publication date :
2018-02-01
ISSN :
2328-9503
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Rett Syndrome (RTT) is a severe neurodevelopmental condition with breathing disorders, affecting around one in 10,000 female births. Desipramine, a noradrenaline reuptake inhibitor, reduced the number of apneas in ...
Show more >Rett Syndrome (RTT) is a severe neurodevelopmental condition with breathing disorders, affecting around one in 10,000 female births. Desipramine, a noradrenaline reuptake inhibitor, reduced the number of apneas in Mecp2-deficient mice, a model of RTT. We planned a phase 2 trial to test its efficacy and its safety on breathing patterns in 36 girls with RTT. The trial was a 6-month, multicenter, randomized, double-blind, placebo-controlled study registered with ClinicalTrials.gov, number NCT00990691. Girls diagnosed according to clinical examination and confirmed by genotyping were randomly assigned in a 1:1:1 ratio to receive 2-3 mg/kg Desipramine per day (high Desipramine), 1-2 mg/kg Desipramine per day (low Desipramine), or a placebo. The primary outcome was the change of apnea hypopnea index (AHI), defined by the number of apnea and hypopnea events per hour, assessed at 6 months from baseline. Intention-to-treat analysis was applied. The median change in AHI from baseline to 6 months was -31 (IQR: -37 to -11) for the high Desipramine, -17.5 (IQR: -31 to 13) for the low Desipramine, and -13 (IQR:-31 to 0) for the placebo group. We did not find any significant difference in these changes between the groups (Pr P This first clinical trial of desipramine did not show clinical efficacy. Although required further studies, the significant correlation between Desipramine concentrations and improvement of AHI provided additional and relevant reasons to test the noradrenergic pathway in RTT.Show less >
Show more >Rett Syndrome (RTT) is a severe neurodevelopmental condition with breathing disorders, affecting around one in 10,000 female births. Desipramine, a noradrenaline reuptake inhibitor, reduced the number of apneas in Mecp2-deficient mice, a model of RTT. We planned a phase 2 trial to test its efficacy and its safety on breathing patterns in 36 girls with RTT. The trial was a 6-month, multicenter, randomized, double-blind, placebo-controlled study registered with ClinicalTrials.gov, number NCT00990691. Girls diagnosed according to clinical examination and confirmed by genotyping were randomly assigned in a 1:1:1 ratio to receive 2-3 mg/kg Desipramine per day (high Desipramine), 1-2 mg/kg Desipramine per day (low Desipramine), or a placebo. The primary outcome was the change of apnea hypopnea index (AHI), defined by the number of apnea and hypopnea events per hour, assessed at 6 months from baseline. Intention-to-treat analysis was applied. The median change in AHI from baseline to 6 months was -31 (IQR: -37 to -11) for the high Desipramine, -17.5 (IQR: -31 to 13) for the low Desipramine, and -13 (IQR:-31 to 0) for the placebo group. We did not find any significant difference in these changes between the groups (Pr P This first clinical trial of desipramine did not show clinical efficacy. Although required further studies, the significant correlation between Desipramine concentrations and improvement of AHI provided additional and relevant reasons to test the noradrenergic pathway in RTT.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CHU Lille
CNRS
Inserm
Université de Lille
CNRS
Inserm
Université de Lille
Collections :
Research team(s) :
Troubles cognitifs dégénératifs et vasculaires
Submission date :
2019-11-27T14:29:43Z