Clinical trial NCT06935630: Comparison of The Effect of 5-MTHF and Folic Acid Supplementation in Increasing Red Blood Cell Folate in Pregnant Women
Official title: Comparison of The Effect of 5-MTHF and Folic Acid Supplementation in Increasing Red Blood Cell Folate in Pregnant Women : A Randomized Controlled Trial Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pregnant Women
Keywords: Interventional
Folic Acid
Pregnant Women
Lead sponsor: Dr. Soetomo General Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Prodia Diacro Laboratories P.T.
name: Simex Pharmaceutical Indonesia
First posted: 2025-04-20
Enrollment: 100
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This randomized controlled trial aims to compare the efficacy of 5-methyltetrahydrofolate (5-MTHF) and folic acid supplementation in increasing red blood cell (RBC) folate levels in pregnant women.

This study will recruit pregnant women and randomly assign them to receive either 5-MTHF or folic acid supplementation. The primary outcome is the difference in RBC folate levels between the two groups at the end of the study. Secondary outcomes include the proportion of women achieving a target RBC folate level of 906 nM, changes in plasma 5-MTHF, homocysteine, and unmetabolized folic acid (UMFA) levels from baseline to month three (M3).

The findings of this study will provide valuable insights into the comparative effectiveness of 5-MTHF and folic acid supplementation in optimizing folate status during pregnancy, potentially informing clinical practice and guidelines. All participants will be provided with detailed information about the study, and their participation will be voluntary. Ethical considerations, including informed consent and data confidentiality, will be strictly adhered to throughout the study.

Detailed description: This prospective, double-blind, randomized controlled trial (RCT) aims to evaluate and compare the efficacy of 5-methyltetrahydrofolate (5-MTHF) and folic acid supplementation in increasing red blood cell (RBC) folate levels among pregnant women in their first trimester. The study is grounded in the understanding that both food folate and folic acid are metabolized into 5-MTHF, the active form of folate essential for DNA synthesis and homocysteine remethylation. Given the established links between folate deficiency, hyperhomocysteinemia, and adverse pregnancy outcomes, including neural tube defects (NTDs), pre-eclampsia, and premature birth, this research seeks to determine if 5-MTHF, as the direct active form, offers superior benefits over traditional folic acid supplementation. The findings will provide crucial insights into optimizing folate supplementation strategies during early pregnancy, potentially improving maternal and fetal health outcomes.

The study will recruit 100 pregnant women aged 25-35 years, with gestational ages between 9-14 weeks, who meet the inclusion criteria of normal BMI (18.5-24.9 kg/m2), hemoglobin levels above 11 g/dL, and a declaration of good health based on prior medical examinations. Participants will be randomly assigned to one of two groups: one receiving 600 mcg (1.35 μmol) of folic acid and the other receiving 1100 mcg (1.35 μmol) of 5-MTHF glucosamine salt (HY-FOLIC®), ensuring an equimolar dosage comparison. Exclusion criteria include pre-existing upper gastrointestinal diseases, history or current use of drugs interacting with folate metabolism (e.g., methotrexate), antiepileptic therapy, or concomitant use of proton pump inhibitors (PPIs), antacids, or H2 receptor blockers within the past three months. This rigorous selection process aims to minimize confounding variables and ensure the internal validity of the study.

The primary outcome of this research is to determine the difference in RBC folate levels between the two supplementation groups at the end of the three-month study period. Secondary outcomes include the proportion of pregnant women in each group achieving an RBC folate level threshold of 906 nM, as well as changes in plasma 5-MTHF, homocysteine, and unmetabolized folic acid (UMFA) levels from baseline to the end of the intervention period. These outcomes will provide a comprehensive assessment of the comparative effectiveness of 5-MTHF and folic acid in improving folate status and related biomarkers in pregnant women. Blood samples will be collected at baseline and at the end of the third month to measure these parameters, ensuring objective and quantifiable data for analysis.

Ethical considerations are paramount in this study. All participants will provide written informed consent prior to enrollment, and the study protocol will be reviewed and approved by an Institutional Review Board (IRB) or equivalent ethics committee. Participant confidentiality will be maintained throughout the study, and data will be anonymized during analysis and reporting. Any potential risks associated with blood sampling or supplementation will be thoroughly explained to participants, and appropriate safety measures will be implemented. Participants will be informed of their right to withdraw from the study at any time without penalty.

The results of this study are expected to contribute significantly to the current understanding of optimal folate supplementation during pregnancy, potentially impacting clinical guidelines and practices. By comparing 5-MTHF and folic acid directly, this research will provide evidence-based recommendations for healthcare providers to ensure adequate folate levels in pregnant women, thereby reducing the risk of adverse pregnancy outcomes and promoting maternal and fetal health.

Eligibility criteria: Inclusion Criteria:

* Pregnant women with a gestational age of 9-14 weeks
* Age: 25 - 35 years old
* Have normal BMI (18.5-24.9 kg/m2)
* Declared healthy based on previous health examinations
* Hb \> 11 g/dl

Exclusion Criteria:

* Pregnant women with upper gastrointestinal disease
* History or current use of drugs interacting with folate metabolism (e.g., Methotrexate)
* History or current use of antiepileptic therapy
* Concomitant use of Proton Pump Inhibitors (PPI), antacid, and AH2 receptor blocker

Primary outcomes:
measure: Change in Red Blood Cell (RBC) Folate Levels
timeFrame: Baseline and Month 3 (End of Intervention)
Secondary outcomes:
measure: Proportion of Participants Achieving Target RBC Folate Level
timeFrame: Month 3 (End of Intervention)
measure: Change in Plasma 5-MTHF Levels
timeFrame: Baseline and Month 3 (End of Intervention)
measure: Change in Plasma Homocysteine Levels
timeFrame: Baseline and Month 3 (End of Intervention)
measure: Change in Plasma UMFA Levels
timeFrame: Baseline and Month 3 (End of Intervention)
Other outcomes:
Locations:
city: Surabaya
country: Indonesia
facility: Mulyorejo Public Health
state: East Java
Study officials:
affiliation: Soetomo General Hospital Surabaya
name: Ernawati Ernawati, Doctor
role: PRINCIPAL_INVESTIGATOR
References: