Folic Acid Supplementation in Children With Sickle Cell Disease
Condition: Anemia, Sickle Cell
MeSH terms: Anemia, Sickle Cell
Study type: Interventional

Summary: 
      Folic acid supplementation (1mg/d) is the standard recommendation for Canadian children with
      Sickle cell disease (SCD), even though it can provide up to six times the recommended intake
      amount for healthy children. There is growing concern that too much folic acid can be
      detrimental to health as high folate levels and circulating unmetabolized folic acid (UMFA),
      which occurs in blood with doses of folic acid as low as 0.2mg/d, have been associated with
      accelerated growth of some pre-cancerous cells, and altered DNA methylation and gene
      expression.

      To inform the efficacy and potential harm of high-dose folic acid supplementation in Canadian
      children with SCD, a double-blind randomized controlled cross-over trial is proposed.
      Children with SCD (n=36, aged 2-19 y) will be recruited from BC Children's Hospital and
      randomized to initially receive 1 mg/d folic acid or a placebo for 12-weeks (wk). After a
      12-wk washout period, treatments will be reversed.
    

Detailed description: 
      Blood samples will be collected at baseline and 12-wk of each treatment period (weeks 12, 24,
      and 36).

      Serum and RBC concentrations of total folate, different folate forms and clinical outcomes
      will be measured at baseline and after each treatment period. Dietary folate intake will be
      assessed at baseline.

      The objective of this study is to determine efficacy and potential harm of folic acid
      supplementation, versus no supplementation, in Canadian children with sickle cell disease.

      It is hypothesized that: (1) there will be no difference in mean RBC folate concentrations
      across folic acid and placebo groups after 12-wk, (2) none of the participants will have
      folate deficiency, and (3) compared to periods of no supplementation, during periods of
      high-dose folic acid supplementation participants will show no difference in clinical
      outcomes, but have higher plasma unmetabolized folic acid concentrations.

      Significance: There is a need to determine if the current clinical practice of high-dose
      folic acid supplementation is efficacious, and warranted.
    

Intervention name(s): Folic Acid Supplement; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 1 milligram folic acid; Placebo
Intervention MeSH terms: Folic Acid
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This research project will consist of a clinical trial in which children with SCD are randomly selected to initially receive 1 mg per day of folic acid (the current standard dose) or a placebo for a 12-week period. Following that, each participant will have a 12 week wash-out period and then treatments are reversed (folic acid supplement or placebo) for 12 weeks. No controls are included in the study as each participant serves as their own control during periods of no supplementation.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Folic Acid; Unmetabolized Folic Acid; Pediatrics