Woodcock Ian R, de Valle Katy, Cairns Anita, Davidson Zoe E, Kean Michael, Varma Nisha, Grobler Anneke, Metz David, Carroll Kate, Dilek Nuran, Heatwole Chad, Ryan Monique M, Delatycki Martin B, Yiu Eppie M
Department of Neurology, The Royal Children's Hospital, Melbourne, Victoria, Australia.
The Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
Pharmacotherapy. 2025 Jun;45(6):341-351. doi: 10.1002/phar.70025. Epub 2025 May 14.
Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive muscle disease with no available disease-modifying therapy. Creatine monohydrate (CrM) has been shown to improve muscle strength in individuals with muscular dystrophies but has not been tested in young people with FSHD. This study aimed to explore the efficacy of CrM on motor function in children with FSHD.
In a randomized placebo-controlled double-blind crossover trial, powdered CrM at a dose of 100 mg/kg/day (maximum 10 g daily) was compared with placebo in two 12-week treatment periods with a 6-week washout between crossover arms. The primary outcome measure was the Motor Function Measure for Neuromuscular Disease (MFM-32) with secondary outcomes assessing safety, endurance, strength, patient-reported outcome measures, and muscle morphology measurements as assessed by whole-body magnetic resonance imaging (MRI).
Thirteen children were enrolled (mean (standard deviation, SD) 12.2 (2.67) years of age) and 11 patients completed both trial treatment periods. In an intention-to-treat analysis, no clinically meaningful difference was seen between treatment groups as measured by the mean difference in MFM-32 (0.19, 95% confidence interval (CI) -0.71 to 1.08). However, there was an improvement in 6-minute walk distance of 27.74 m (95% CI -1.41 to 56.88) and trends to improvement in the FSHD-Composite Outcome Measure for Pediatrics (FSHD-COM Peds), 10 meter walk/run, and in MRI measures. There were no serious adverse events. Serum creatinine increased by a mean 12.63 μmol/L (95% CI 1.14 to 24.12) post-CrM treatment, though this was presumed to reflect increased creatinine production. No participants discontinued CrM due to adverse events.
CrM is safe and well tolerated in children with FSHD. Although CrM had no effect on motor function as measured by the MFM-32 compared with placebo, there were trends toward improvement in the 6-minute walk distance and other secondary outcome measures. This study confirms the feasibility of conducting clinical trials in children with FSHD. Further assessment of the efficacy of CrM in pediatric FSHD is warranted in a larger randomized controlled clinical trial. Future studies may benefit from stratifying population cohorts according to functional ability or by MRI fat infiltration measurements.
面肩肱型肌营养不良症（FSHD）是一种罕见的进行性肌肉疾病，目前尚无有效的疾病修正疗法。一水肌酸（CrM）已被证明可改善肌营养不良症患者的肌肉力量，但尚未在患有FSHD的年轻人中进行测试。本研究旨在探讨CrM对FSHD患儿运动功能的疗效。
在一项随机安慰剂对照双盲交叉试验中，将剂量为100mg/kg/天（最大每日10g）的CrM粉末与安慰剂在两个12周的治疗期内进行比较，交叉组之间有6周的洗脱期。主要结局指标是神经肌肉疾病运动功能测量量表（MFM-32），次要结局指标评估安全性、耐力、力量、患者报告的结局指标以及通过全身磁共振成像（MRI）评估的肌肉形态测量指标。
共纳入13名儿童（平均（标准差，SD）年龄为12.2（2.67）岁），11名患者完成了两个试验治疗期。在意向性分析中，通过MFM-32的平均差异测量，治疗组之间未观察到具有临床意义的差异（0.19，95%置信区间（CI）-0.71至1.08）。然而，6分钟步行距离改善了27.74m（95%CI -1.41至56.88），小儿FSHD综合结局测量量表（FSHD-COM Peds）、10米步行/跑步以及MRI测量指标有改善趋势。未发生严重不良事件。CrM治疗后血清肌酐平均升高12.63μmol/L（95%CI 1.14至24.12），不过这被认为反映了肌酐生成增加。没有参与者因不良事件而停用CrM。
CrM在FSHD患儿中安全且耐受性良好。尽管与安慰剂相比，CrM对通过MFM-32测量的运动功能没有影响，但6分钟步行距离和其他次要结局指标有改善趋势。本研究证实了在FSHD患儿中进行临床试验的可行性。有必要在更大规模的随机对照临床试验中进一步评估CrM在小儿FSHD中的疗效。未来的研究可能会受益于根据功能能力或MRI脂肪浸润测量对人群队列进行分层。
