Grieco Joseph C, Ciarlone Stephanie L, Gieron-Korthals Maria, Schoenberg Mike R, Smith Amanda G, Philpot Rex M, Heussler Helen S, Banko Jessica L, Weeber Edwin J
Department of Molecular Pharmacology and Physiology, University of South Florida, Morsani College of Medicine, 12901 Bruce B Downs Boulevard, Tampa, FL, 33612, USA.
Department of Pediatrics, University of South Florida, Morsani College of Medicine, 12901 Bruce B Downs Boulevard, Tampa, FL, 33612, USA.
BMC Neurol. 2014 Dec 10;14:232. doi: 10.1186/s12883-014-0232-x.
Minocycline, a member of the tetracycline family, has a low risk of adverse effects and an ability to improve behavioral performance in humans with cognitive disruption. We performed a single-arm open-label trial in which 25 children diagnosed with Angelman syndrome (AS) were administered minocycline to assess the safety and tolerability of minocycline in this patient population and determine the drug's effect on the cognitive and behavioral manifestations of the disorder.
Participants, age 4-12 years old, were randomly selected from a pool of previously screened children for participation in this study. Each child received 3 milligrams of minocycline per kilogram of body weight per day for 8 weeks. Participants were assessed during 3 study visits: baseline, after 8-weeks of minocycline treatment and after an 8-week wash out period. The primary outcome measure was the Bayley Scales of Infant and Toddler Development 3rd Edition (BSID-III). Secondary outcome measures included the Clinical Global Impressions Scale (CGI), Vineland Adaptive Behavior Scales 2nd Edition (VABS-II), Preschool Language Scale 4th Edition (PLS-IV) and EEG scores. Observations were considered statistically significant if p < 0.05 using ANOVA and partial eta squared (η(2)) was calculated to show effect size. Multiple comparisons testing between time points were carried out using Dunnett's post hoc testing.
Significant improvement in the mean raw scores of the BSID-III subdomains communication and fine motor ability as well as the subdomains auditory comprehension and total language ability of the PLS-IV when baseline scores were compared to scores after the washout period. Further, improvements were observed in the receptive communication subdomain of the VABS-II after treatment with minocycline. Finally, mean scores of the BSID-III self-direction subdomain and CGI scale score were significantly improved both after minocycline treatment and after the wash out period.
The clinical and neuropsychological measures suggest minocycline was well tolerated and causes improvements in the adaptive behaviors of this sample of children with Angelman syndrome. While the optimal dosage and the effects of long-term use still need to be determined, these findings suggest further investigation into the effect minocycline has on patients with Angelman syndrome is warranted.
NCT01531582 - clinicaltrials.gov.
米诺环素是四环素家族的一员，不良反应风险较低，且能够改善认知功能受损人群的行为表现。我们开展了一项单臂开放标签试验，对25名被诊断为天使综合征（AS）的儿童使用米诺环素，以评估米诺环素在该患者群体中的安全性和耐受性，并确定该药物对该疾病认知和行为表现的影响。
从之前筛选的儿童群体中随机选取4至12岁的参与者参与本研究。每个儿童每天每千克体重服用3毫克米诺环素，持续8周。在3次研究访视期间对参与者进行评估：基线期、米诺环素治疗8周后以及8周的洗脱期后。主要结局指标是贝利婴幼儿发展量表第三版（BSID-III）。次要结局指标包括临床总体印象量表（CGI）、文兰适应行为量表第二版（VABS-II）、学前语言量表第四版（PLS-IV）和脑电图评分。使用方差分析（ANOVA），若p < 0.05，则观察结果被认为具有统计学意义，并计算偏 eta 平方（η(2)）以显示效应大小。使用邓尼特事后检验在时间点之间进行多重比较检验。
将基线分数与洗脱期后的分数进行比较时，BSID-III子领域沟通和精细运动能力以及PLS-IV子领域听觉理解和总语言能力的平均原始分数有显著改善。此外，米诺环素治疗后，VABS-II的接受性沟通子领域有改善。最后，米诺环素治疗后和洗脱期后，BSID-III自我导向子领域的平均分数和CGI量表分数均有显著改善。
临床和神经心理学测量表明，米诺环素耐受性良好，可改善该样本天使综合征儿童的适应性行为。虽然最佳剂量和长期使用的效果仍有待确定，但这些发现表明有必要进一步研究米诺环素对天使综合征患者的影响。
NCT01531582 - clinicaltrials.gov。
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