杜氏肌营养不良症是生命限制。心肌病,这主要发生在人生的第二个十年,是死亡的主要原因.治疗选择仍然有限。TAMDMD(NCT03354039)试验评估了运动功能,肌肉力量和结构,实验室生物标志物,79名患有基因证实的杜氏肌营养不良症的非卧床男孩的安全性,6.5-12岁,每天服用他莫昔芬20mg或安慰剂,共48周。在这个事后分析中,本研究检索了在一个研究中心招募的非住院患者治疗前后的现有超声心动图数据,并对其进行比较.来自14名患者的数据,中位数11(四分位数间距,IQR,11-12)岁可用。分配给安慰剂(n=7)或他莫昔芬(n=7)的参与者的基线人口统计学特征相似。安慰剂组的左心室舒张末期直径(中位数和IQR)在基线时为39(38-41)mm,在研究结束时为43(38-44)mm,而他莫昔芬组治疗后基线为44(41-46)mm,治疗后为41(37-46)mm。安慰剂组治疗前左心室缩短分数为35%(32-38%),治疗后为33%(32-36%),而在他莫昔芬组中,基线时为34%(33-34%),研究结束时为35%(33-35%)。未检测到安全信号。
结论:这一假设产生的事后分析表明,他莫昔芬超过48周的耐受性良好,可能有助于维持Duchenne型肌营养不良患者的心脏结构和功能。进一步的研究是合理的。
结果:政府标识符:EudraCT2017-004554-42,NCT03354039已知:•杜兴氏肌营养不良症(DMD)是生命受限的。心肌病发生在生命的第二个十年,是死亡的主要原因。治疗选择仍然有限。•他莫昔芬减少小鼠的心脏纤维化并改善人诱导的多能干细胞衍生的心肌细胞中的心肌细胞功能。
背景:•在对14名男孩的TAMDMD试验进行的事后分析中,中位年龄11岁,用他莫昔芬或安慰剂治疗48周,治疗耐受性良好。•改善左心室尺寸和更好的收缩功能保存的视觉趋势产生了他莫昔芬在DMD心肌病中潜在有益作用的假设。
Duchenne muscular dystrophy is life-limiting. Cardiomyopathy, which mostly ensues in the second decade of life, is the main cause of death. Treatment options are still limited. The TAMDMD (NCT03354039) trial assessed motor function, muscle strength and structure, laboratory biomarkers, and safety in 79 ambulant boys with genetically confirmed Duchenne muscular dystrophy, 6.5-12 years of age, receiving either daily
tamoxifen 20 mg or placebo for 48 weeks. In this post-hoc analysis, available echocardiographic data of ambulant patients recruited at one study centre were retrieved and compared before and after treatment. Data from 14 patients, median 11 (interquartile range, IQR, 11-12) years of age was available. Baseline demographic characteristics were similar in participants assigned to placebo (n = 7) or
tamoxifen (n = 7). Left ventricular end-diastolic diameter in the placebo group (median and IQR) was 39 (38-41) mm at baseline and 43 (38-44) mm at study end, while it was 44 (41-46) mm at baseline and 41 (37-46) mm after treatment in the
tamoxifen group. Left ventricular fractional shortening in the placebo group was 35% (32-38%) before and 33% (32-36%) after treatment, while in the tamoxifen group it was 34% (33-34%) at baseline and 35% (33-35%) at study end. No safety signals were detected.
CONCLUSIONS: This hypothesis-generating post-hoc analysis suggests that
tamoxifen over 48 weeks is well tolerated and may help preserving cardiac structure and function in Duchenne muscular dystrophy. Further studies are justified.
RESULTS: gov Identifier: EudraCT 2017-004554-42, NCT03354039 What is known: • Duchenne muscular dystrophy (DMD) is life-limiting. Cardiomyopathy ensues in the second decade of life and is the main cause of death. Treatment options are still limited. •
Tamoxifen reduced cardiac fibrosis in mice and improved cardiomyocyte function in human-induced pluripotent stem cell-derived cardiomyocytes.
BACKGROUND: • In this post-hoc analysis of the TAMDMD trial among 14 boys, median 11 years of age, treated with either tamoxifen or placebo for 48 weeks, treatment was well-tolerated. • A visual trend of improved left-ventricular dimensions and better systolic function preservation generates the hypothesis of a potential beneficial effect of tamoxifen in DMD cardiomyopathy.