RT Journal Article
T1 A randomized placebo controlled clinical trial to evaluate the efficacy and safety of minocycline in patients with Angelman syndrome (A-MANECE study)
A1 Ruiz-Antoran, Belén
A1 Sancho-López, Aranzazu
A1 Cazorla-Calleja, Rosario
A1 López-Pájaro, Luis Fernando
A1 Leiva, Ágata
A1 Iglesias-Escalera, Gema
A1 Marín-Serrano, María Esperanza
A1 Rincón-Ortega, Marta
A1 Lara-Herguedas, Julián
A1 Rossignoli-Palomeque, Teresa
A1 Valiente-Rodríguez, Sara
A1 González Marqués, Javier
A1 Román-Riechmann, Enriqueta
A1 Avendaño-Solá, Cristina
AB Background: Minocycline is an old tetracycline antibiotic that has shown antiinflammatory and antiapoptotic properties in different neurological disease mouse models. Previous single arm study in humans demonstrated benefits in individuals with Angelman Syndrome (AS); however, its efficacy in patients with Angelman Syndrome has not been assessed in a controlled trial. This was a randomized, double-blind, placebo-controlled, crossover trial in individuals with AS, aged 6 years to 30 years (n = 32, mean age 12 [SD 6·29] years). Participants were randomized to minocycline or placebo for 8 weeks and then switched to the other treatment (a subset of 22 patients) or to receive minocycline for up to 16 weeks (10 patients). After week 16, all patients entered a wash-out 8-week follow-up period.Results: Thirty-six subjects were screened and 34 were randomized. Thirty two subjects (94·1%) completed at least the first period and all of them completed the full trial. Intention-to-treat analysis demonstrated the lack of significantly greater improvements in the primary outcome, mean changes in age equivalent of the development index of the Merrill-Palmer Revised Scale after minocycline compared with placebo (1·90 ± 3·16 and 2·00 ± 3·28, respectively, p = 0·937). Longer treatment duration up to 16 weeks did not result in better treatment outcomes (1·86 ± 3·35 for 8 weeks treatment vs 1·20 ± 5·53 for 16 weeks treatment, p = 0·667). Side effects were not significantly different during minocycline and placebo treatments. No serious adverse events occurred on minocycline.Conclusions: Minocycline treatment for up to 16 weeks in children and young adults with AS resulted in lack of significant improvements in development indexes compared to placebo treatment. Treatment with minocycline appears safe and well tolerated; even if it cannot be completely ruled out that longer trials might be required for a potential minocycline effect to be expressed, available results and lack of knowledge on the actual mechanism of action do not support this hypothesis. Trial registration: European Clinical Trial database (EudraCT 2013-002154-67), registered 16th September 2013; US Clinical trials database (NCT02056665), registered 6th February 2014.
PB BMC
SN 1750-1172
YR 2018
FD 2018-08-20
LK https://hdl.handle.net/20.500.14352/99340
UL https://hdl.handle.net/20.500.14352/99340
LA eng
NO Ruiz-Antoran, B., Sancho-López, A.,  Cazorla-Calleja, R., López-Pájaro, L.F., Leiva, A., Iglesias-Escalera, G., Marín-Serrano, M.E., Rincón-Ortega, M., Lara-Herguedas, J., Rossignoli-Palomeque, T., Valiente-Rodríguez, S., González-Marqués, J., Román-Riechmann, E., Avendaño-Solá, C. A randomized placebo controlled clinical trial to evaluate the efficacy and safety of minocycline in patients with Angelman syndrome (A-MANECE study). Orphanet Journal of Rare Diseases. 2018 13:144. https://doi.org/10.1186/s13023-018-0891-6
DS Docta Complutense
RD 9 abr 2025