NCT03981029

FACT Biomarker Subgroup Analysis

Folic Acid Clinical Trial (FACT): Biomarker Subgroup Analysis

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 51 (actual)
• Sponsor: Ottawa Hospital Research Institute · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

The FACT Biomarker Subgroup Analysis is a pilot study of mothers who participated in the Folic Acid Clinical Trial (FACT, NCT01355159). This subgroup analysis aims to determine the effect of high-dose folic acid supplementation in pregnancy on maternal folate status and subsequent impact on risk for pre-eclampsia.

Detailed description

The Folic Acid Clinical Trial (FACT) was developed to conclusively determine the effect of high dose folic acid supplementation in pregnancy on the prevention of preeclampsia (PE) in a randomized controlled trial (RCT) design. The primary objective of the FACT Biomarker Subgroup Analysis is to determine the folate status and its impact on risk for PE in a subgroup of women participating in FACT. Our secondary objectives are to: i) To determine serum vitamin B6 and B12 status, modifiers of folate metabolism, and their impact on risk for PE in women participating in the FACT ii) To determine plasma homocysteine status, a folate-responsive biomarker for PE risk, and its relationship with risk for PE in women participating in the FACT iii) To determine the modifying effect of single nucleotide polymorphisms (SNPs) in key folate metabolic enzymes (MTHFR, MTHFD1, MTR) on PE risk in women participating in the FACT iv) To determine the effect of folic acid supplementation and folate status on biomarkers of PE (sFLT, sENG, PlGF) and their association with PE risk in women participating in the FACT Folate biomarker analyses will provide key information to identify modifiers of the response to folic acid treatment and elucidate the mechanism(s) underlying the relationship between folic acid treatment and PE risk. Folate status will vary in response to folic acid treatment depending on a number of factors including compliance in taking the study supplement, folate intake from the diet (natural folate and folic acid used for enrichment), vitamin B12 status, and genetic polymorphisms in enzymes involved in folate metabolism that have been shown to effect placental development/function. As such, variation in the response to folic acid treatment may account for differences in observed PE risk. Folic acid supplementation may also reduce homocysteine, its related endothelial dysfunction and consequently reduce PE risk. In addition, homocysteine metabolism is dependent on vitamins B12 and B6, the deficiency of which can result in hyperhomocysteinemia. Thus, homocysteine, B12 and B6 will each be evaluated. Lastly, it will be useful to assess biomarkers of placental health and PE risk (sFlt-1, sEng, PlGF) that are found in maternal circulation and determine their association with folate intake and status.

Conditions

• Pre-Eclampsia

Interventions

Type	Name	Description
OTHER	4.0mg Folic Acid received through participation in FACT (NCT01355159)	Participants in this study received either daily high-dose folic acid supplementation during pregnancy OR placebo through their participation in FACT (NCT01355159). Details of the FACT Folic Acid intervention are provided below: Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid
OTHER	Placebo received through participation in FACT	Participants in this study received either daily high-dose folic acid supplementation during pregnancy OR placebo through their participation in FACT (NCT01355159). Details of the FACT Folic Acid placebo are provided below: Placebo x 4 tablets will be taken daily by oral administration.

Timeline

• Start date: 2011-12-19
• Primary completion: 2016-07-01
• Completion: 2016-09-01
• First posted: 2019-06-10
• Last updated: 2024-05-20
• Results posted: 2024-05-20

Locations

4 sites across 1 country: Canada