Trial Outcomes & Findings for FACT Biomarker Subgroup Analysis (NCT NCT03981029)
NCT ID: NCT03981029
Last Updated: 2024-05-20
Results Overview
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).
Recruitment status
COMPLETED
Target enrollment
51 participants
Primary outcome timeframe
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.
Results posted on
2024-05-20
Participant Flow
Participant milestones
| Measure |
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.
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
|
FACT Placebo Treatment Group
Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily placebo supplementation during pregnancy.
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.
|
|---|---|---|
|
Overall Study
STARTED
|
19
|
32
|
|
Overall Study
COMPLETED
|
19
|
31
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
FACT Biomarker Subgroup Analysis
Baseline characteristics by cohort
| Measure |
FACT High-dose Folic Acid Treatment Group
n=19 Participants
Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily high-dose folic acid supplementation during pregnancy.
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
|
FACT Placebo Treatment Group
n=31 Participants
Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily placebo supplementation during pregnancy.
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.
|
Total
n=50 Participants
Total of all reporting groups
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|---|---|---|---|
|
Age, Continuous
|
32 years
n=99 Participants
|
32 years
n=107 Participants
|
32 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=99 Participants
|
31 Participants
n=107 Participants
|
50 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Caucasian race
|
18 Participants
n=99 Participants
|
28 Participants
n=107 Participants
|
46 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Other race
|
1 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Region of Enrollment
Canada
|
19 participants
n=99 Participants
|
31 participants
n=107 Participants
|
50 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 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.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).
Outcome measures
| Measure |
FACT High-dose Folic Acid Treatment Group
n=19 Participants
Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily high-dose folic acid supplementation during pregnancy.
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
|
FACT Placebo Treatment Group
n=31 Participants
Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily placebo supplementation during pregnancy.
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.
|
|---|---|---|
|
Folate Status
RBC folate
|
2701 nmol/L
Interval 2559.0 to 3017.0
|
2686 nmol/L
Interval 2311.0 to 3047.0
|
|
Folate Status
Serum total folate by protein binding assay
|
105 nmol/L
Interval 57.0 to 183.0
|
67.1 nmol/L
Interval 58.5 to 89.0
|
|
Folate Status
Serum total folate by LC-MS/MS
|
148.4 nmol/L
Interval 110.4 to 181.2
|
122.8 nmol/L
Interval 99.5 to 136.0
|
|
Folate Status
5-MethylTHF
|
126.6 nmol/L
Interval 98.8 to 158.6
|
108.6 nmol/L
Interval 96.4 to 123.2
|
|
Folate Status
unmetabolized folic acid
|
4.6 nmol/L
Interval 2.5 to 33.8
|
1.9 nmol/L
Interval 0.9 to 4.1
|
|
Folate Status
THF
|
3 nmol/L
Interval 1.0 to 12.6
|
2.4 nmol/L
Interval 0.6 to 8.5
|
|
Folate Status
5-formylTHF
|
1.3 nmol/L
Interval 0.8 to 1.6
|
1.4 nmol/L
Interval 0.6 to 1.6
|
|
Folate Status
5,10-MethenylTHF
|
0.9 nmol/L
Interval 0.5 to 1.6
|
0.8 nmol/L
Interval 0.2 to 1.0
|
|
Folate Status
MeFox
|
6.9 nmol/L
Interval 3.6 to 10.1
|
5.0 nmol/L
Interval 2.4 to 8.0
|
SECONDARY outcome
Timeframe: 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.Population: Two participants in the High-dose Folic Acid Treatment Group and one participant in the Placebo Treatment Group had missing data for this outcome.
Maternal homocysteine concentrations will be determined.
Outcome measures
| Measure |
FACT High-dose Folic Acid Treatment Group
n=17 Participants
Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily high-dose folic acid supplementation during pregnancy.
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
|
FACT Placebo Treatment Group
n=30 Participants
Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily placebo supplementation during pregnancy.
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.
|
|---|---|---|
|
Homocysteine Status
|
6 nmol/L
Interval 4.6 to 7.0
|
6.4 nmol/L
Interval 5.6 to 7.8
|
SECONDARY outcome
Timeframe: Taken at one time point between 24 and 26 completed weeks gestation.Population: For Vitamin B-12 measurement, sample data are not available for one participant in the high-dose folic acid treatment group, and one participant in the placebo treatment group. Missing data are due to insufficient sample volume or compromised sample quality.
Status of modifiers of folate metabolism will be determined by Vitamin B6 and B12 concentrations
Outcome measures
| Measure |
FACT High-dose Folic Acid Treatment Group
n=18 Participants
Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily high-dose folic acid supplementation during pregnancy.
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
|
FACT Placebo Treatment Group
n=30 Participants
Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily placebo supplementation during pregnancy.
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.
|
|---|---|---|
|
Status of Modifiers of Folate metabolism_vitamin B-12
|
217.5 pmol/L
Interval 191.0 to 271.0
|
208.5 pmol/L
Interval 192.0 to 277.0
|
SECONDARY outcome
Timeframe: 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.Angiogenic potential will be determined from measurement of maternal circulating s-FLT-1, s-ENG-1 and placental growth factor concentrations.
Outcome measures
| Measure |
FACT High-dose Folic Acid Treatment Group
n=19 Participants
Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily high-dose folic acid supplementation during pregnancy.
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
|
FACT Placebo Treatment Group
n=31 Participants
Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily placebo supplementation during pregnancy.
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.
|
|---|---|---|
|
Angiogenic Potential
Placenta growth factor (PlGF)
|
421.4 pg/mL
Interval 220.4 to 653.2
|
331.2 pg/mL
Interval 214.2 to 580.7
|
|
Angiogenic Potential
soluble fms-like tyrosin kinase 1 (sFlt-1)
|
862.9 pg/mL
Interval 630.2 to 1382.2
|
812 pg/mL
Interval 624.5 to 1381.0
|
|
Angiogenic Potential
soluble endoglin (sEng-1)
|
961.5 pg/mL
Interval 688.7 to 1250.1
|
1061.0 pg/mL
Interval 669.9 to 1322.8
|
SECONDARY outcome
Timeframe: Taken at one time point between 24 and 26 completed weeks gestation.Population: The baseline distribution of MTHFR (C677T) genotype frequencies, ie, CC, TT, and CT are describe in each row.
Status of modifiers of folate metabolism will be determined by frequency of single nucleotide polymorphisms (SNPs) in the key folate metabolic enzyme MTHFR
Outcome measures
| Measure |
FACT High-dose Folic Acid Treatment Group
n=19 Participants
Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily high-dose folic acid supplementation during pregnancy.
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
|
FACT Placebo Treatment Group
n=31 Participants
Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily placebo supplementation during pregnancy.
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.
|
|---|---|---|
|
Status of Modifiers of Folate metabolism_MTHFR Genotype (C677T)
CC
|
7 Participants
|
12 Participants
|
|
Status of Modifiers of Folate metabolism_MTHFR Genotype (C677T)
CT
|
9 Participants
|
15 Participants
|
|
Status of Modifiers of Folate metabolism_MTHFR Genotype (C677T)
TT
|
3 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Taken at one time point between 24 and 26 completed weeks gestation.Population: For Vitamin B-6 (pyridoxal 5-phosphate), sample data are not available for one participant in the high-dose folic acid treatment group. Missing data are due to insufficient sample volume or compromised sample quality.
Status of modifiers of folate metabolism will be determined by Vitamin B6 and B12 concentrations
Outcome measures
| Measure |
FACT High-dose Folic Acid Treatment Group
n=18 Participants
Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily high-dose folic acid supplementation during pregnancy.
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
|
FACT Placebo Treatment Group
n=31 Participants
Consenting study participants who, through their participation in FACT (NCT01355159) are randomized to receive daily placebo supplementation during pregnancy.
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.
|
|---|---|---|
|
Status of Modifiers of Folate metabolism_ Vitamin B6 (Pyridoxal 5-phosphate)
|
44.3 nmol/L
Interval 19.0 to 71.4
|
40.0 nmol/L
Interval 21.2 to 80.9
|
Adverse Events
FACT High-dose Folic Acid Treatment Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
FACT Placebo Treatment Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place