- Title
- L-carnitine supplementation for muscle weakness and fatigue in children with neurofibromatosis type 1: A Phase 2a clinical trial
- Creator
- Vasiljevski, Emily R.; Burns, Joshua; Baldwin, Jennifer N.; Little, David G.; Schindeler, Aaron; Bray, Paula; Donlevy, Gabrielle; Mudge, Anita J.; Jones, Kristi J.; Summers, Matthew A.; Biggin, Andrew; Munns, Craig F.; McKay, Marnee J.
- Relation
- American Journal of Medical Genetics Part A Vol. 185, Issue 10, p. 2976-2985
- Publisher Link
- http://dx.doi.org/10.1002/ajmg.a.62392
- Publisher
- John Wiley & Sons, Inc.
- Resource Type
- journal article
- Date
- 2021
- Description
- Reduced muscle tone, muscle weakness, and physical fatigue can impact considerably on quality of life for children with neurofibromatosis type 1 (NF1). Human muscle biopsies and mouse models of NF1 deficiency in muscle show intramyocellular lipid accumulation, and preclinical data have indicated that L-carnitine supplementation can ameliorate this phenotype. The aim of this study is to examine whether daily L-carnitine supplementation is safe and feasible, and will improve muscle strength and reduce fatigue in children with NF1. A 12-week Phase 2a trial was conducted using 1000 mg daily oral levocarnitine tartrate supplementation. Recruited children were between 8 and 12 years old with a clinical diagnosis of NF1, history of muscle weakness and fatigue, and naïve to L-carnitine. Primary outcomes were safety (self-reporting, biochemical testing) and compliance. Secondary outcomes included plasma acylcarnitine profiles, functional measures (muscle strength, long jump, handwriting speed, 6-minute-walk test [6MWT]), and parent-reported questionnaires (PedsQL™, CBCL/6–18). Six children completed the trial with no self-reported adverse events. Biochemical tests for kidney and liver function were normal, and the average compliance was 95%. Plasma acylcarnitine levels were low, but within a range not clinically linked to carnitine deficiency. For strength measures, there was a mean 53% increase in dorsiflexion strength (95% confidence interval [CI] 8.89–60.75; p = 0.02) and mean 66% increase in plantarflexion strength (95% CI 12.99–134.1; p = 0.03). In terms of muscle performance, there was a mean 10% increase in long jump distance (95% CI 2.97–16.03; p = 0.01) and 6MWT distance (95% CI 5.88–75.45; p = 0.03). Comparison with the 1000 Norms Project data showed a significant improvement in Z-score for all of these measures. Parent reports showed no negative impact on quality of life, and the perceived benefits led to the majority of individuals remaining on L-carnitine after the study. Twelve weeks of L-carnitine supplementation is safe and feasible in children with NF1, and a Phase 3 trial should confirm the efficacy of treatment.
- Subject
- children; fatigue; L-carnitine; muscle weakness; neurofibromatosis
- Identifier
- http://hdl.handle.net/1959.13/1501266
- Identifier
- uon:55114
- Identifier
- ISSN:1552-4825
- Language
- eng
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