Folic Acid Supplementation in Children With Sickle Cell Disease

Anemia, Sickle Cell Clinical Trial

Official title:

Folic Acid Supplementation in Children With Sickle-Cell Disease: A Randomized Double-Blind Cross-Over Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04011345
• Other study ID #: H18-02981
• Status: Completed
• Phase: N/A
• Start date: November 23, 2020
• Est. completion date: October 31, 2022

Study information

• Verified date: August 2023
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: October 31, 2022
• Est. primary completion date: October 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 19 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell

Intervention

Dietary Supplement:
• Folic Acid Supplement
1 milligram folic acid
• Placebo
Placebo

Locations

Country	Name	City	State
Canada	BC Children's Hospital	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University of British Columbia

Country where clinical trial is conducted

Canada, 

References & Publications (1)

Williams BA, McCartney H, Adams E, Devlin AM, Singer J, Vercauteren S, Wu JK, Karakochuk CD. Folic acid supplementation in children with sickle cell disease: study protocol for a double-blind randomized cross-over trial. Trials. 2020 Jun 29;21(1):593. doi: 10.1186/s13063-020-04540-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Red Blood Cell Folate Concentration	Biochemical folate status marker (nmol/L)	12 weeks
Primary	Red Blood Cell Folate Concentration	Biochemical folate status marker (nmol/L)	36 weeks
Secondary	Serum Folate Concentration	Biochemical folate status marker (nmol/L)	12 weeks
Secondary	Serum Folate Concentration	Biochemical folate status marker (nmol/L)	36 weeks
Secondary	Plasma Unmetabolized Folic Acid Concentration	Biochemical folate marker (nmol/L)	12 weeks
Secondary	Plasma Unmetabolized Folic Acid Concentration	Biochemical folate marker (nmol/L)	36 weeks
Secondary	S-adenosyl-methionine Concentration	Biochemical folate metabolite (µmol/L)	12 weeks
Secondary	S-adenosyl-methionine Concentration	Biochemical folate metabolite (µmol/L)	36 weeks
Secondary	S-adenosyl-homocysteine Concentration	Biochemical folate metabolite (µmol/L)	12 weeks
Secondary	S-adenosyl-homocysteine Concentration	Biochemical folate metabolite (µmol/L)	36 weeks
Secondary	Total homocysteine Concentration	Biochemical folate metabolite (µmol/L)	12 weeks
Secondary	Total homocysteine Concentration	Biochemical folate metabolite (µmol/L)	36 weeks
Secondary	Acute Pain Crises	Participant self-reported occurrence (# of episodes, and severity of episodes)	12 weeks
Secondary	Acute Pain Crises	Participant self-reported occurrence (# of episodes, and severity of episodes)	36 weeks
Secondary	Megaloblastic anemia	Determined by hemoglobin and Mean Corpuscular Volume (MCV) concentrations below/above age-specific hematological cut-offs	12 weeks
Secondary	Megaloblastic anemia	Determined by hemoglobin and Mean Corpuscular Volume (MCV) concentrations below/above age-specific hematological cut-offs	36 weeks

External Links

•   Study protocol