A randomized placebo controlled clinical trial to evaluate the efficacy and safety of minocycline in patients with Angelman syndrome (A-MANECE study).
A randomized placebo controlled clinical trial to evaluate the efficacy and safety of minocycline in patients with Angelman syndrome (A-MANECE study).
复制标题
DOI：
10.1186/s13023-018-0891-6
复制
发表时间：
2018-08-20
影响因子：
3.7
通讯作者：
Avendaño-Solá C
中科院分区：
文献类型：
--
作者：
Ruiz-Antoran B;Sancho-López A;Cazorla-Calleja R;López-Pájaro LF;Leiva Á;Iglesias-Escalera G;Marín-Serrano ME;Rincón-Ortega M;Lara-Herguedas J;Rossignoli-Palomeque T;Valiente-Rodríguez S;González-Marques J;Román-Riechmann E;Avendaño-Solá C
二甲胺四环素是一种古老的四环素抗生素，在不同的神经系统疾病小鼠模型中显示出抗炎和抗细胞凋亡的特性。先前的人类单臂研究证明了Angelman综合征（AS）患者的益处；然而，其对Angelman综合征患者的疗效尚未在对照试验中进行评估。这是一项随机、双盲、安慰剂对照、交叉试验，研究对象为6岁至30岁的AS患者（n = 32，平均年龄12岁[SD 6·29]岁）。参与者随机接受米诺环素或安慰剂治疗8周，然后切换到其他治疗（22名患者）或接受米诺环素治疗长达16周（10名患者）。第16周后，所有患者进入洗脱期8周随访期。筛选36名受试者，随机选取34名受试者。32名受试者（94.1%）至少完成了第一期试验，并全部完成了整个试验。意向治疗分析显示，与安慰剂相比，米诺环素治疗后的主要结局没有明显的改善，年龄当量的平均变化相当于Merrill-Palmer修订量表的发展指数（分别为1.90±3.16和2.00±3.28,p = 0.937）。治疗时间延长至16周并没有带来更好的治疗结果（8周治疗1.86±3.35 vs 16周治疗1.20±5.53,p = 0.667）。米诺环素治疗和安慰剂治疗的副作用无显著差异。米诺环素未发生严重不良事件。与安慰剂治疗相比，米诺环素治疗长达16周的儿童和青年AS患者在发育指标方面缺乏显着改善。米诺环素治疗似乎安全且耐受性良好；即使不能完全排除可能需要更长时间的试验才能表达米诺环素的潜在作用，现有的结果和对实际作用机制的缺乏知识也不支持这一假设。欧洲临床试验数据库（EudraCT 2013-002154-67），注册于2013年9月16日；美国临床试验数据库（NCT02056665），注册于2014年2月6日。本文的在线版本（10.1186/s13023-018-0891-6）包含补充资料，仅供授权用户使用。
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. 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. 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. European Clinical Trial database (EudraCT 2013-002154-67), registered 16th September 2013; US Clinical trials database (NCT02056665), registered 6th February 2014. The online version of this article (10.1186/s13023-018-0891-6) contains supplementary material, which is available to authorized users.
登录
查看更多内容
DOI：
10.1097/dbp.0b013e318287cd17
发表时间：
2013-04-01
影响因子：
2.4
作者：
Leigh, Mary Jacena S.;Nguyen, Danh V.;Hagerman, Randi J.
通讯作者：
Hagerman, Randi J.
影响因子：
3.7
作者：
Wheeler AC;Sacco P;Cabo R
通讯作者：
Cabo R
DOI：
10.1002/ajmg.1320280407
发表时间：
1987-12-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
MAGENIS, RE;BROWN, MG;LAFRANCHI, S
通讯作者：
LAFRANCHI, S
影响因子：
14.5
作者：
Brundula, V;Rewcastle, NB;Yong, VW
通讯作者：
Yong, VW
影响因子：
64.5
作者：
Margolis SS;Salogiannis J;Lipton DM;Mandel-Brehm C;Wills ZP;Mardinly AR;Hu L;Greer PL;Bikoff JB;Ho HY;Soskis MJ;Sahin M;Greenberg ME
通讯作者：
Greenberg ME