FACT Biomarker Subgroup Analysis

NCT03981029 | Completed Results DMC

• 1 other identifier: 2011649-01H
• Study Type: observational
• Target: 51
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Pre-Eclampsia

Keywords

Folate; One Carbon Metabolism; Preeclampsia; Folic Acid; Pregnancy

Outcome Measures

Primary Outcomes (1)

• Folate Status

  The primary outcome measure is maternal folate status. Folate status will be determined by: 1. Red blood cell (RBC) folate concentrations. 2. Total serum folate concentrations. 3. The relative contribution of folate vitamers to total serum folate concentrations (unmetabolized folic acid, tetrahydrofolic acid, 5,10-methenylTHF, 5-formylTHF, 5-methylTHF and MeFox).

  From FACT randomization at 8-16 weeks gestation to date of sample collection taken at one time point between 24 and 26 completed weeks gestation.

Secondary Outcomes (5)

• Homocysteine Status

  From FACT randomization at 8-16 weeks gestation to date of sample collection taken at one time point between 24 and 26 completed weeks gestation.

• Status of Modifiers of Folate metabolism_vitamin B-12

  Taken at one time point between 24 and 26 completed weeks gestation.

• Angiogenic Potential

  From FACT randomization at 8-16 weeks gestation to date of sample collection taken at one time point between 24 and 26 completed weeks gestation.

• Status of Modifiers of Folate metabolism_MTHFR Genotype (C677T)

  Taken at one time point between 24 and 26 completed weeks gestation.

• Status of Modifiers of Folate metabolism_ Vitamin B6 (Pyridoxal 5-phosphate)

  Taken at one time point between 24 and 26 completed weeks gestation.

Study Arms (2)

FACT High-dose folic acid treatment group

Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily high-dose folic acid supplementation during pregnancy.

Other: 4.0mg Folic Acid received through participation in FACT (NCT01355159)

FACT Placebo treatment group

Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily placebo supplementation during pregnancy.

Other: Placebo received through participation in FACT

Interventions

4.0mg Folic Acid received through participation in FACT (NCT01355159) OTHER

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

FACT High-dose folic acid treatment group

Placebo received through participation in FACT OTHER

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.

FACT Placebo treatment group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The FACT Biomarker Subgroup Analysis is a pilot study that aims to determine the folate status and its impact on risk for pre-eclampsia in a subgroup of women participating in FACT (NCT01355159). Women participating in FACT (NCT01355159) will be eligible to participate.

You may qualify if:

• Capability of subject to comprehend and comply with study requirements
• ≥ 18 years of age at time of consent
• Subject is taking ≤1.1 mg of folic acid daily at the time of randomization
• Live fetus (documented positive fetal heart prior to randomization)
• Gestational age between 8+0 and 16+6 weeks of pregnancy (Gestational age (GA) of subjects will be calculated based on the first day of the last menstrual period (LMP) or ultrasound performed before 12+6. If early ultrasound and LMP dates differ by ≤ 7 days, base GA estimate on LMP date; if \> 7 days, use early \< 12+6 ultrasound)
• Subject plans to give birth in a participating hospital site
• Pregnant subjects must fulfill at least one of the following identified risk factors for pre-eclampsia (PE):
• Pre-existing hypertension (documented evidence of diastolic blood pressure ≥ 90 mmHg on two separate occasions or at least 4 hours apart prior to randomization, or use of antihypertensive medication during this pregnancy specifically for the treatment of hypertension prior to randomization)
• Pre-pregnancy diabetes (documented evidence of Type I or type II DM)
• Twin pregnancy
• Documented evidence of history of PE in a previous pregnancy
• BMI \> 35 kg/m2 within 3 months prior to this pregnancy and up to randomization of this pregnancy (documented evidence of height and weight to calculate BMI is required)

You may not qualify if:

• Known history or presence of any clinically significant disease or condition which would be a contraindication to folic acid supplementation of up to 5 mg daily for the duration of pregnancy
• Known major fetal anomaly or fetal demise
• History of medical complications, including: renal disease with altered renal function, epilepsy, cancer, or use of folic acid antagonists such as valproic acid
• Individual who is currently enrolled or has participated in another clinical trial or who received an investigational drug within 3 months of the date of randomization (unless approved by the Trial Coordinating Centre)
• Known presence of: Alcohol abuse (≥ 2 drinks per day) or alcohol dependence, Illicit drug/substance use and/or dependence, Known hypersensitivity to folic acid, Multiple Pregnancy (triplets or more), Participation in this study in a previous pregnancy

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (4)

The Moncton Hospital

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1Y 4E9, Canada

Location

Health Canada

Ottawa, Ontario, Canada

Location

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Related Links

• High Dose Folic Acid Supplementation Throughout Pregnancy for Preeclampsia Prevention (FACT) ClinicalTrials.gov registration

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral Whole Blood, Plasma, Serum

MeSH Terms

Conditions

Pre-Eclampsia

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Limitations and Caveats

Selection bias and generalizability: convenience sample from a larger trial of individuals at high risk for preeclampsia Small sample size Lack of baseline folate measurements and the single time-point evaluation of folate status: prevents analysis of changes in folate status and 1-carbon metabolism over the course of pregnancy Samples were non-fasting and information on the timing of sample collection relative to ingestion of the daily folic acid supplements was not collected

Results Point of Contact

• Title: Alysha Harvey
• Organization: Ottawa Hospital Research Institute

alyharvey@ohri.ca

613-737-8899

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2019
• First Posted: June 10, 2019
• Study Start: December 19, 2011
• Primary Completion: July 1, 2016
• Study Completion: September 1, 2016
• Last Updated: May 20, 2024
• Results First Posted: May 20, 2024

Record last verified: 2019-06

Locations

CA (4)