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Randomized Controlled Trial
. 2025 Jun;45(6):341-351.
doi: 10.1002/phar.70025. Epub 2025 May 14.

Effect of creatine monohydrate on motor function in children with facioscapulohumeral muscular dystrophy: A multicenter, randomized, double-blind placebo-controlled crossover trial

Ian R Woodcock  1   2   3 , Katy de Valle  1   2   4 , Anita Cairns  5 , Zoe E Davidson  1   2   6 , Michael Kean  7 , Nisha Varma  7 , Anneke Grobler  2   3 , David Metz  2   8   9 , Kate Carroll  1   2 , Nuran Dilek  10 , Chad Heatwole  10 , Monique M Ryan  1   2 , Martin B Delatycki  3   11   12 , Eppie M Yiu  1   2   3
Affiliations
Randomized Controlled Trial

Effect of creatine monohydrate on motor function in children with facioscapulohumeral muscular dystrophy: A multicenter, randomized, double-blind placebo-controlled crossover trial

Ian R Woodcock et al. Pharmacotherapy. 2025 Jun.

Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Keywords: FSHD; creatine monohydrate; neuromuscular; pediatrics.

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Conflict of interest statement

Dr. Woodcock has received honoraria for work performed, including educational activities and attendance at advisory board meetings from pharmaceutical companies Avidity, Biogen, Novartis, Roche, and Solid Biosciences. Dr. Woodcock has received grants for research work from FSHD Global Research Foundation, FSHD Society, Fulcrum Therapeutics, and the NIH. Dr. Woodcock has been the principal investigator on a number of industry‐sponsored clinical trials, including Biogen, Catabasis, Dyne Therapeutics, EryDel, Novartis, Percheron Therapeutics, Pfizer, PTC, Roche, and Sarepta. None of these disclosures affected the work Dr. Woodcock performed on this clinical trial. Dr. Ryan has since left the above affiliations to take up public office. Dr. Davidson has received research grant funding from Pfizer. Dr. Yiu has received advisory board honoraria from Biogen and Roche, and has received research support from Biogen, Roche, Pfizer, and PTC therapeutics unrelated to the content of this manuscript. Dr. Yiu has been the principal investigator on a number of industry‐sponsored clinical trials. None of these disclosures affected the work Dr. Yiu performed on this clinical trial. Prof. Delatycki has received grant awards from NHMRC and is the principal investigator in industry‐sponsored clinical trials including trials sponsored by Rearta and PTC. All other authors report no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Creatine monohydrate in FSHD clinical trial CONSORT trial schema.
FIGURE 2
FIGURE 2
95% Confidence intervals of mean difference of creatine monohydrate versus placebo in outcome measures where an increase in score equates to less disease severity. 6MWT, Six‐Minute Walk Test; MFM, Motor Function Measure for Neuromuscular Disease; PUL, Performance of the Upper Limb.
FIGURE 3
FIGURE 3
95% Confidence intervals of mean difference of creatine monohydrate versus placebo in outcome measures where a decrease in score equates to less disease severity. FSHD‐COM Peds, FSHD‐Composite Outcome Measure for Pediatrics; FSHD‐CS, FSHD Clinical Score; FSHD‐CSS, FSHD Clinical Severity Scale.
See this image and copyright information in PMC

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