Is Natural Folate as Effective as Synthetic Folic Acid in Increasing Serum and Red Blood Cell Folate Concentrations During Pregnancy? A Proof-of-concept Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Concentration of serum folate levels
研究概览
简要总结
In this two-arm, double-blind randomized pilot study, the investigators will recruit 60 generally healthy, low-risk pregnant women aged 19-42 years living in Vancouver, Canada. Participants will be randomized to supplement with either 0.6 mg/day folic acid or an equimolar dose (0.625 mg/day) of (6S)-5-methyltetrahydrofolic acid for 16-weeks of their pregnancy. Randomization will occur at 8-21 weeks gestation (after neural tube closure) to reduce the risk of harm should the natural folate prove less effective. All participants will also receive a prenatal multivitamin not containing any form of folate, to ensure adequacy of other nutrients (e.g. iron) required during pregnancy. Three-hour fasting venous blood samples will be collected at baseline and endline to measure serum and red blood cell folate, unmetabolized folic acid and other related biomarkers. Women will be given the option to continue supplementing until 1-week postpartum, and provide a small (3mL) breastmilk sample and blood sample in order to measure differences in folates in breastmilk and postpartum folate. These pilot data will be used to inform a definitive trial regarding the most effective form of folate supplementation for mothers and their babies.
详细描述
A sample size of 50 women (25 in each group) are required to reliably estimate the distributions of serum and red blood cell folate. Thus, to account for drop outs or loss to follow up, a total of 60 women (30 in each group) will be recruited.
Aim 1: To establish the mean ± standard deviation change in serum folate, red blood cell folate, and unmetabolized folic acid levels in each group following supplementation with (6S)-5-methyltetrahydrofolic acid or folic acid for 16-weeks of pregnancy.
Aim 2: To determine participation recruitment and retention rate, the most effective recruitment strategies for this population, and adherence to study protocol (to inform a definitive trial).
Exploratory Aims: To explore differences in proposed clinical effects associated with folic acid supplementatation (immunity, gene methylation) and differences in biomarkers that function closely with folate in one carbon metabolism (B-vitamins, choline and its metabolites [betaine, dimethylglycine]) and which support overall blood health (ferritin, inflammation). In the postpartum phase, we will quantify proportion of total breastmilk folate as folic acid in each group, evaluate correlation of maternal postpartum plasma unmetabolized folic acid and breastmilk folic acid, and to evaluate RBC folate concentrations following delivery in each group. Differences in breastmilk biomarkers associated with folate (choline, human milk oligosaccharides, and breastmilk microbiome) will be explored.
Women may undergo informed consent process anytime <21 weeks gestation. Once participants indicate that they are interested in participating in the trial, the participant will be given a study ID, and a baseline visit will be scheduled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 19 Years 至 42 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Pregnant woman (singleton pregnancy)
- •Living in the Greater Vancouver area and willing to travel to the University of British Columbia for study visits
- •<21 weeks gestation
- •19-42 years of age
- •willing to participate
排除标准
- •Have a pre-existing medical condition known to impact maternal folate status (malabsorptive of irritable bowel disease, active celiac disease, gastric bypass surgery, atrophic gastritis, epilepsy, advanced liver disease, kidney dialysis, type 1 or 2 diabetes mellitus, sickle cell trait/anemia)
- •Lifestyle factors known to impact maternal folate status (smoking, alcohol overuse, non-prescription drug use/abuse)
- •Are medium to high risk for development of an NTD-affected pregnancy (applies to women or their male partner: personal or family history [parents or siblings] of other folate sensitive congenital anomalies, personal NTD history or a previous NTD-affected pregnancy)
- •Are taking medications known to interfere with B-vitamin metabolism (Chloramphenicol, Methotrexate, Metformin, Sulfasalazine, Phenobarbital, Phenytoin, Primidone, Triamterene, Barbiturates)
- •pre-pregnancy body mass index ≥30 kg/m2
- •allergic to any of the supplement ingredients
结局指标
主要结局
Concentration of serum folate levels
时间窗: concentrations at both baseline (8-21 weeks gestation), endline (24-37 weeks gestation), and postpartum
nmol/L; Reflects recent status or dietary intake
Concentration of red blood cell folate levels
时间窗: concentrations at both baseline (8-21 weeks gestation), endline (24-37 weeks gestation), and postpartum
nmol/L; Reflects longer term status (e.g. previous 3-4 months)
Concentration of unmetabolized folic acid (and other folate forms: THF, 5-Methyl-THF, 5-formyl-THF, and 5,10-methenyl-THF)
时间窗: concentrations at both baseline (8-21 weeks gestation), endline (24-37 weeks gestation), and postpartum
nmol/L; unmetabolized folic acid is not incorporated into RBCs, rather it circulates in plasma
次要结局
- Concentration of dimethylglycine(concentrations at both baseline (8-21 weeks gestation), endline (24-37 weeks gestation))
- Concentration of pyridoxal-5'-phosphate(concentrations at both baseline (8-21 weeks gestation), endline (24-37 weeks gestation))
- Concentration of S-adenosyl-methionine(concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation))
- Concentration of total vitamin B-12(concentrations at both baseline (8-21 weeks gestation), endline (24-37 weeks gestation))
- Concentration of vitamin B2(concentrations at both baseline (8-21 weeks gestation), endline (24-37 weeks gestation))
- Concentration of betaine(concentrations at both baseline (8-21 weeks gestation), endline (24-37 weeks gestation))
- Concentration of cysteine(concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation))
- Concentration of S-adenosyl-homocysteine(concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation))
- Concentration of total homocysteine(concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation))
- Breastmilk fatty acids & choline forms (free choline, betaine, phosphocholine, glycerophosophocholine)(Collection at 1 week postpartum)
- Concentration of choline(concentrations at both baseline (8-21 weeks gestation), endline (24-37 weeks gestation))
- Collection of peripheral blood mononuclear layer cells(Collection at both baseline (8-21 weeks gestation), endline (24-37 weeks gestation))
- Concentration of unmetabolized folic acid in breastmilk (and other folate forms: THF, 5-Methyl-THF, 5-formyl-THF, and 5,10-methenyl-THF)(Collection at 1 week postpartum)
- Concentration of methionine(concentrations at both baseline (8-21 weeks gestation) and endline (24-37 weeks gestation))
- Folate binding protein in breastmilk(Collection at 1 week postpartum)
- Breastmilk human milk oligosaccharides and breastmilk microbiome(Collection at 1 week postpartum)
- Complete blood count(Baseline (8-21 weeks gestation), endline (24-37 weeks gestation), and postpartum)
- Markers of Iron and Inflammation(Baseline (8-21 weeks gestation),and endline (24-37 weeks gestation))
研究者
Crystal Karakochuk
Assistant Professor
University of British Columbia