PREconception Folic Acid Clinical Efficacy (PREFACE) Trial (PREFACE)

A study to help understand what forms of folic acid are most effective to increase folate status during pregnancy for the best protection against neural tube defects

Study Overview

• Status: Not yet recruiting
• Conditions: Pregnancy; Folate; Folate Bioavailability; Clinical Trials
• Intervention / Treatment: Dietary supplement: 5-MTHF (5-methyltetrahydrofolate); Dietary supplement: Folic Acid

Detailed Description

A multisite randomized controlled trial to determine whether supplementation with (6S)-5-methyltetrahydrofolic acid (5-MTHF) is at least as effective as synthetic folic acid in increasing maternal folate status for protection against neural tube defects (NTDs).

• Study Type: Interventional
• Enrollment (Estimated): 272
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Crystal D Karakochuk, PhD; Phone Number: 604-822-0421; Email: crystal.karakochuk@ubc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Non-pregnant females who are:
• Currently trying to become pregnant;
• Aged 19-42 years;
• Low risk for an NTD-affected pregnancy

Exclusion Criteria:

• Trying to conceive for ≥6 months (as ~90% of pregnancies occur after 6 months of trying);
• Diagnosed ovulatory disorders (polycystic ovary syndrome, endometriosis, or menstrual irregularity);
• More than 2 miscarriages in the past year;
• Undergoing fertility assistance (including current IVF or intrauterine insemination);
• Pre-existing medical condition known to impact maternal folate status (malabsorptive and inflammatory bowel diseases, active celiac disease, gastric bypass surgery, type 1 or 2 diabetes mellitus);
• Lifestyle factors known to impact maternal folate status (current smoking, >6 alcoholic drinks per week, recreational drug use);
• On the female or male side of those trying to conceive: personal NTD history, previous NTD-affected pregnancy, or personal or family history of other folate sensitive congenital anomalies;
• Use of folate-inhibiting medications (Chloramphenicol, Methotrexate, Metformin, Sulfasalazine, Phenobarbital, Phenytoin, Primidone, Triamterene, Barbiturates).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5MTHF	Dietary supplement: 5-MTHF (5-methyltetrahydrofolate); 0.625 mg/d (6S)-5-MTHF
Active Comparator: Synthetic folic acid; Folic acid	Dietary supplement: Folic Acid; folic acid (0.6 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RBC folate	•Maternal RBC folate concentrations (nmol/L)	At 6 (± 2) wks gestation (approximate time of neural tube closure)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal plasma placental growth factor (pg/mL)	A novel biomarker with increasing use in clinical practice due to a discriminatory capacity for fetal growth restriction vs a small, but healthy fetus	At 18 (± 1) and 30 (± 1) wks gestation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Human milk total folate concentrations	Unmetabolized folic acid, reduced folate forms (nmol/L), and folate binding protein	At 4 weeks postpartum

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: University of Saskatchewan
• Investigators: Principal Investigator: Crystal D Karakochuk, PhD, The University of British Columbia; Principal Investigator: Kelsey M Cochrane, PhD, University of Saskatchewan

Study record dates

Study Major Dates

• Study Start (Estimated): January 31, 2025
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): January 31, 2030

Study Registration Dates

• First Submitted: October 11, 2024
• First Submitted That Met QC Criteria: October 11, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): October 21, 2024
• Last Update Submitted That Met QC Criteria: October 17, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Folic acid; Folate; 5-MTHF; Placental Growth Factor; Methylfolate; RBC Folate
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Folic Acid
• Other Study ID Numbers: H24-01716; UBC CREB H24-01716 (Other Identifier: The University of British Columbia (UBC) Clinical Research Ethics Board (CREB))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No