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Williams, Brock A.; McCartney, Heather; Adams, Erin; Devlin, Angela M.; Singer, Joel; Vercauteren, Suzanne; Wu, John K.; Karakochuk, Crystal D.

BioMed Central

Background: Sickle cell disease (SCD) is a genetic disorder which causes dysfunctional red blood cells (RBC) and is thought to increase requirements for folate, an essential B vitamin, due to increased RBC production and turnover in the disease. High-dose supplementation with 1–5 mg/d folic acid, synthetic folate, has been the standard recommendation for children with SCD. There is concern about whether children with SCD need such high doses of folic acid, following mandatory folic acid fortification of enriched grains in Canada, and advancements in medical therapies which extend the average lifespan of RBCs. In animal and human studies, high folic acid intakes (1 mg/d) have been associated with accelerated growth of some cancers, and the biological effects of circulating unmetabolized folic acid (UMFA), which can occur with doses of folic acid ≥ 0.2 mg/d, are not fully understood. The objective of this study is to determine efficacy of, and alterations in folate metabolism from high-dose folic acid in children with SCD during periods of folic acid supplementation versus no supplementation. Methods: In this double-blind randomized controlled cross-over trial, children with SCD (n = 36, aged 2–19 years) will be randomized to either receive 1 mg/d folic acid, the current standard of care, or a placebo for 12 weeks. After a 12-week washout period, treatments will be reversed. Total folate concentrations (serum and RBC), different folate forms (including UMFA), folate-related metabolites, and clinical outcomes will be measured at baseline and after treatment periods. The sum of the values measured in the two periods will be calculated for each subject and compared across the two sequence groups by means of a test for independent samples for the primary (RBC folate concentrations) and secondary (UMFA) outcomes. Dietary intake will be measured at the beginning of each study period. Discussion: As the first rigorously designed clinical trial in children with SCD, this trial will inform and assess current clinical practice, with the ultimate goal of improving nutritional status of children with SCD. Trial registration: ClinicalTrials.gov NCT04011345 . Registered on July 8, 2019

Article

eng

Vancouver : University of British Columbia Library

10.14288/1.0392009

Land and Food Systems, Faculty of; Medicine, Faculty of; Other UBC; Non UBC; Pathology and Laboratory Medicine, Department of; Pediatrics, Department of; Population and Public Health (SPPH), School of

10.1186/s13063-020-04540-7

Faculty

http://creativecommons.org/licenses/by/4.0/