Folic Acid Supplementation in Children With Sickle-Cell Disease: A Randomized Double-Blind Cross-Over Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 2
- 主要终点
- Red Blood Cell Folate Concentration
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double-blind clinical trials, so neither participants nor medical care providers will be aware of the participants group assignment in order to limit bias, changes in dietary habits, or medical treatment. The outcomes assessor will also be unaware of participant assignment in order to limit bias in analysis of samples.
入排标准
- 年龄范围
- 2 Years 至 19 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
结局指标
主要结局
Red Blood Cell Folate Concentration
时间窗: 36 weeks
Biochemical folate status marker (nmol/L)
次要结局
- Plasma Unmetabolized Folic Acid Concentration(36 weeks)
- S-adenosyl-methionine Concentration(36 weeks)
- S-adenosyl-homocysteine Concentration(36 weeks)
- Acute Pain Crises(36 weeks)
- Megaloblastic anemia(36 weeks)
- Serum Folate Concentration(36 weeks)
- Total homocysteine Concentration(36 weeks)
研究者
Crystal Karakochuk
Associate Professor
University of British Columbia