Academic Journal
A randomized placebo controlled clinical trial to evaluate the efficacy and safety of minocycline in patients with Angelman syndrome (A-MANECE study)
| العنوان: | A randomized placebo controlled clinical trial to evaluate the efficacy and safety of minocycline in patients with Angelman syndrome (A-MANECE study) |
|---|---|
| المؤلفون: | Belén Ruiz-Antoran, Aranzazu Sancho-López, Rosario Cazorla-Calleja, Luis Fernando López-Pájaro, Ágata Leiva, Gema Iglesias-Escalera, Maria Esperanza Marín-Serrano, Marta Rincón-Ortega, Julián Lara-Herguedas, Teresa Rossignoli-Palomeque, Sara Valiente-Rodríguez, Javier González-Marques, Enriqueta Román-Riechmann, Cristina Avendaño-Solá |
| المصدر: | Orphanet Journal of Rare Diseases, Vol 13, Iss 1, Pp 1-10 (2018) |
| بيانات النشر: | BMC, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Medicine |
| مصطلحات موضوعية: | Angelman syndrome, Treatment, Minocycline, Developmental changes, Pharmacological intervention, Medicine |
| الوصف: | Abstract 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1750-1172 |
| Relation: | http://link.springer.com/article/10.1186/s13023-018-0891-6; https://doaj.org/toc/1750-1172 |
| DOI: | 10.1186/s13023-018-0891-6 |
| URL الوصول: | https://doaj.org/article/009879ee08ee409083a78b68dfda0da2 |
| رقم الانضمام: | edsdoj.009879ee08ee409083a78b68dfda0da2 |
| قاعدة البيانات: | Directory of Open Access Journals |
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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. 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