Folic Acid Supplementation in Children With Sickle Cell Disease

University of British Columbia

Status: Completed

Conditions: Anemia, Sickle Cell

Treatments: Dietary Supplement: Folic Acid Supplement; Dietary Supplement: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04011345

H18-02981

Details and patient eligibility

About

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.

Full 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.

Enrollment: 31 patients

Sex: All

Ages: 2 to 19 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Individuals with SCD aged 2-19 y attending British Columbia Children's Hospital
• Individuals having received routine daily supplementation of folic acid for the prior 12-weeks

Exclusion criteria

• Individuals receiving a blood transfusion in the prior 12-weeks
• Individuals allergic to any components of the supplement (cellulose, methylcellulose, magnesium stearate, and/or titanium dioxide)
• Individuals presenting with megaloblastic anemia in the prior 12-weeks
• Individuals with pulmonary, renal and/or cardiac complications (severe or recurrent acute chest syndrome)
• Individuals routinely taking medications known to interfere with B vitamin metabolism (chloramphenicol, methotrexate, metformin, sulfasalazine, phenobarbital, primidone, triamterene, barbiturates)
• Individuals who are currently pregnant, planning to become pregnant in the next 9-months, or currently breastfeeding
• Individuals who have participated in a clinical research trial in the previous 30 days
• Individuals who have donated blood in the previous 30 days
• Individuals with unstable medical conditions or unstable laboratory results.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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31 participants in 2 patient groups

Folic Acid Supplement [Phase 1]

Other group

Description:

Phase 1: Folic acid supplement (1 mg per day) for 12 weeks; Phase 2: Wash-out period (no supplement or placebo) for 12 weeks; Phase 3: Placebo for 12 weeks

Treatment:

Dietary Supplement: Placebo

Dietary Supplement: Folic Acid Supplement

Placebo [Phase 1]

Other group

Description:

Phase 1: Placebo for 12 weeks; Phase 2: Wash-out period (no supplement or placebo) for 12 weeks; Phase 3: Folic acid supplement (1 mg per day) for 12 weeks

Treatment:

Dietary Supplement: Placebo

Dietary Supplement: Folic Acid Supplement