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Mancini J, Dubus JC, Jouve E, et al. Effect of desipramine on patients with breathing disorders in RETT syndrome. Ann Clin Transl Neurol. 2017;5(2):118-127doi: 10.1002/acn3.468.
Mancini, J., Dubus, J. C., Jouve, E., Roux, J. C., Franco, P., Lagrue, E., Castelnau, P., Cances, C., Chaix, Y., Rougeot-Jung, C., Cornu, C., Desportes, V., Vallée, L., Bahi-Buisson, N., Truillet, R., Attolini, L., Villard, L., Blin, O., & Micallef, J. (2018). Effect of desipramine on patients with breathing disorders in RETT syndrome. Annals of clinical and translational neurology, 5(2), 118-127. https://doi.org/10.1002/acn3.468
Mancini, Josette, et al. "Effect of desipramine on patients with breathing disorders in RETT syndrome." Annals of clinical and translational neurology vol. 5,2 (2018): 118-127. doi: https://doi.org/10.1002/acn3.468
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, Vallée 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. PMID: 29468173; PMCID: PMC5817841.
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Ann Clin Transl Neurol. 2017 Dec 27;5(2):118-127. doi: 10.1002/acn3.468. eCollection 2018 Feb.

Effect of desipramine on patients with breathing disorders in RETT syndrome.

Annals of clinical and translational neurology

Josette Mancini, Jean-Christophe Dubus, Elisabeth Jouve, Jean-Christophe Roux, Patricia Franco, Emmanuelle Lagrue, Pierre Castelnau, Claude Cances, Yves Chaix, Christelle Rougeot-Jung, Catherine Cornu, Vincent Desportes, Louis Vallée, Nadia Bahi-Buisson, Romain Truillet, Laurence Attolini, Laurent Villard, Olivier Blin, Joëlle Micallef

Affiliations

  1. Neuropediatric Unit Aix Marseille University Children Hospital APHM, Timone, Neurosciences Institute Marseille France.
  2. Pneumology Pediatric Unit Aix Marseille University Children Hospital CNRS URMITE 6236A PHM Marseille France.
  3. Department of Pharmacology F-CRIN Orphan DEV Timone Neurosciences Institute Aix Marseille University CNRS INTAPHM, CIC CPCET CHU Timone Marseille France.
  4. Aix Marseille University INSERM, GMGF UMR_S 910 Marseille France.
  5. Neuropediatric Ward Hypnology Unit Lyon University Civil Hospices of Lyon INSERM U628 Lyon France.
  6. Neuropediatrics and Handicap Department Tours University INSERM, UMR U930 Imaging and Brain, CHRU Tours Tours France.
  7. Neuropediatric Unit Neuro Imaging Center Toulouse University Children Hospital CHU PURPANUMR 1214 Toulouse France.
  8. Lyon University National Reference Center for Rare Diseases with Intellectual Disability HFME Hospices Civils de Lyon Lyon France.
  9. CNRS UMR 5304 ISC Lyon France.
  10. Department of Pharmacotoxicology Clinical Investigation Center Hospices Civils de Lyon INSERM 1407 Lyon France.
  11. Lyon University CNRS UMR 5558 Lyon France.
  12. Department of Neuropediatrics Lille North 2 University CHRU Hôpital Roger Salengro Lille France.
  13. Imagine Institute and INSERM UMR-1163 Embryology and Genetics of Congenital Malformations Pediatric Neurology Paris Descartes - Sorbonne Paris Cité University Necker Enfants Malades University Hospital AP-HP Paris France.

PMID: 29468173 PMCID: PMC5817841 DOI: 10.1002/acn3.468

Abstract

OBJECTIVE: 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.

METHODS: 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.

RESULTS: 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 (

INTERPRETATION: 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.

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