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Trial record 9 of 144 for:    folic acid AND pregnancy NOT (male OR men)

Folic Acid Supplementation in Pregnant Women: Dose Response (FAPREG)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by University of Georgia
Sponsor:
Collaborators:
University of Florida
Emory University
Cornell University
Information provided by (Responsible Party):
Lynn B. Bailey, PhD, University of Georgia
ClinicalTrials.gov Identifier:
NCT02124642
First received: April 24, 2014
Last updated: NA
Last verified: April 2014
History: No changes posted
  Purpose

The proposed study is a double-blind randomized controlled trial in healthy pregnant women (BMI 18.5 - 29.9 kg/m2, age 18 - 40 yr) receiving prenatal care at Athens Regional Midwifery clinic (ARMC).

The primary goal of the proposed study is to determine relative changes in blood folate and DNA methylation levels in response to 2 different supplemental doses of folic acid one of which will provide the Institute of Medicine's recommended folate intake for pregnant women and the second will provide a higher dose as routinely taken by pregnant women in over-the-counter prenatal supplements.

The specific aims of the study are:

  1. to compare maternal serum and red blood cell (RBC) folate levels and % change in women taking either 400 or 800 mcg/day of supplemental folic acid from the first prenatal visit (< 10 weeks) through delivery;
  2. to compare the infant's cord blood folate levels in response to different maternal folic acid intakes (400 mcg/d vs 800 mcg/d);
  3. to determine relative differences in the levels of oxidized folic acid in maternal and infant blood in response to 400 or 800 mcg/d folic acid dose, and
  4. to determine genome wide and gene specific DNA methylation response in pregnant women receiving prenatal supplements containing either 400 or 800 mcg folic acid per day

Condition Intervention
Pregnancy
Dietary Supplement: Folic acid, 400 mcg/day
Dietary Supplement: Folic acid 800 mcg/day

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Folic Acid Supplementation in Pregnant Women: Dose Response

Resource links provided by NLM:


Further study details as provided by University of Georgia:

Primary Outcome Measures:
  • Serum folate [ Time Frame: Baseline (Initial Prenatal Visit), 28 and 36 weeks gestation, delivery ] [ Designated as safety issue: No ]
    Change in serum folate concentrations in response to supplementation during pregnancy with one of two levels of folic acid will be determined by microbiological assay using Lactobacillus rhamnosus. Cord blood serum folate at delivery will also be determined by the microbiological assay. Differences in serum folate response to the two levels of folic acid supplementation will be compared.

  • Red blood cell (RBC) folate [ Time Frame: Baseline (Initial Prenatal Visit), 28 and 36 weeks gestation, delivery ] [ Designated as safety issue: No ]
    Change in red blood cell (RBC) folate concentrations in response to supplementation during pregnancy with one of two levels of folic acid will be determined by microbiological assay using Lactobacillus rhamnosus. Cord blood RBC folate at delivery will also be determined by the microbiological assay. Differences in RBC folate response to the two levels of folic acid supplementation will be compared.

  • Serum folic acid [ Time Frame: Baseline (Initial Prenatal Visit), 28 and 36 weeks gestation, delivery ] [ Designated as safety issue: No ]
    Change in serum folic acid concentrations in response to supplementation during pregnancy with one of two levels of folic acid will be determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cord blood serum folic acid at delivery will also be determined by LC-MS/MS. Differences in serum folic acid in response to the two levels of folic acid supplementation will be compared.

  • Gene-specific DNA methylation [ Time Frame: Baseline (Initial Prenatal Visit), 28 and 36 weeks gestation, delivery ] [ Designated as safety issue: No ]
    Change in DNA methylation in response to folic acid supplementation during pregnancy will be determined in DNA isolated from whole blood. Illumina Infinum HumanMethylatio450 bead chip microarrays will be used to assess changes in multiple methylation sites of specific genes within regulatory pathways for folate metabolism and/or development. Differences in DNA methylation in response to the two levels of folic acid supplementation will be compared.


Secondary Outcome Measures:
  • Cell-type-specific DNA methylation [ Time Frame: Baseline (Initial Prenatal Visit), 28 and 36 weeks gestation, delivery ] [ Designated as safety issue: No ]
    Change in DNA methylation in response to folic acid supplementation during pregnancy will be determined in DNA isolated from specific white blood cell types obtained by antibody/magnetic technology. Illumina Infinum HumanMethylatio450 bead chip microarrays will be used to assess changes in multiple methylation sites of specific genes within regulatory pathways for folate metabolism and/or development. Differences in DNA methylation in response to the two levels of folic acid supplementation will be compared.

  • Infant birth weight [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Birth weight information will be obtained from medical records

  • Infant length [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Length at birth will be obtained from medical records

  • Infant head circumference [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Infant head circumference will be obtained from medical records.

  • Apgar score [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    Apgar score of the infant will be obtained from medical records.


Estimated Enrollment: 200
Study Start Date: May 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Folic acid, 400 mcg/day
A daily 400 microgram (mcg) dose of folic acid will be taken orally, along with the recommended intake for pregnancy of other vitamins, minerals and docosahexaenoic acid (DHA), beginning at enrollment until delivery. The 400 mcg dose approximates the current Recommended Dietary Allowance (RDA) for pregnant women of 600 mcg Dietary Folate Equivalents (400 mcg folic acid ≈ 600 mcg DFEs; conversion factor based on higher bioavailability of folic acid is: 1 mcg folic acid = 1.7 mcg DFE).
Dietary Supplement: Folic acid, 400 mcg/day
The supplement regime for this arm will consist of (1) a women's multivitamin/ multimineral (MVM) supplement containing 400 mcg folic acid, (2) a capsule containing 200 mg DHA and (3) a capsule formulated to contain 10 mg iron (which represents the difference in the amount of iron in the women's MVM formulation and that in prenatal MVM supplements).
Experimental: Folic acid, 800 mcg/day
A daily 800 microgram (mcg) dose of folic acid will be taken orally, along with the recommended intake for pregnancy of other vitamins, minerals and docosahexaenoic acid (DHA), beginning at enrollment until delivery. The 800 microgram dose, which is considerably higher than the current RDA, represents an amount commonly found in over-the-counter prenatal vitamin formulations.
Dietary Supplement: Folic acid 800 mcg/day
The supplement regime for this arm will consist of (1) a women's multivitamin/ multimineral (MVM) supplement containing 400 mcg folic acid, (2) a capsule containing 200 mg DHA and (3) a capsule formulated to contain 10 mg iron (which represents the difference in the amount of iron in the women's MVM formulation and that in prenatal MVM supplements) and 400 mcg folic acid.

Detailed Description:

The study will be conducted in healthy women with a BMI within the ranges of 18.5 - 35.0 kg/m2. There will be two treatment groups: (1) one group taking 400 mcg per day of folic acid as part of a prenatal supplement, beginning at study enrollment (< 10 weeks gestational age) and (2) a second group taking 800 mcg per day of folic acid as part of the prenatal supplement. Both groups will be provided identical composition of prenatal supplements other than folic acid content. Repeated measures of outcome variables will be determined in blood samples collected at various times during pregnancy and at delivery. Due to the role of prenatal supplementation in helping maintain optimal nutrition status throughout pregnancy, there will be no placebo control.

Women will be recruited through the Athens Regional Medical Center Midwifery Practice and all blood draws associated with this study will be conducted during scheduled prenatal visits. The research protocol is consistent with the standard of care provided by the clinic and will not affect the prenatal services provided to the research participants. Following consent at the first prenatal visit, participants will be randomly assigned to receive prenatal supplements containing either 400 or 800 mcg of folic acid (all other ingredients at unmodified concentrations). The 400 mcg dose approximates the current Recommended Dietary Allowance (RDA) for pregnant women of 600 mcg Dietary Folate Equivalents (400 mcg folic acid ≈ 600 mcg DFEs; conversion factor based on higher bioavailability of folic acid is: 1 mcg folic acid = 1.7 mcg DFE). The higher dose of 800 mcg folic acid represents an amount commonly found in over-the-counter prenatal supplements. Women will be asked to take the supplements daily throughout the duration of gestation and to follow their standard prenatal diet, with the exception of avoiding highly fortified (> 100% RDA) ready-to-eat cereals and fortified energy/snack bars and drinks, due to their high folic acid content.

At the first visit, the participants will be instructed in the use of a dietary recall data collection sheet (food diary) which they will be asked to complete during specific time points during the study. Each set of dietary recalls will include information for three 24-hr periods on non-consecutive days including one weekend day. Dietary recall information will be obtained at approximately weeks 16 and 32 of gestation. This will permit assessment of typical dietary intake of total calories and specific nutrients, including folate.

Blood samples will be collected, in the non-fasting state, at the first, 28 week and 36 week prenatal visits and from the mother and cord blood at delivery for determination of primary outcome measures.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy women with singleton pregnancy
  • < 10 weeks gestation at enrollment
  • body mass index 18.5 - 35.0 kg/m2
  • willingness to comply with study protocol ( i.e. take assigned daily prenatal vitamin; complete diet recall and study questionnaire)
  • not consuming super-fortified ready-to-eat cereal products (with > 100% RDA for folate per serving)

Exclusion Criteria:

  • BMI < 18.5 or > 35.0 kg/m2
  • use of prescription drugs
  • anemia
  • chronic disease (diabetes, hypertension, epilepsy, cancer, kidney disease, cardiovascular disease)
  • acute illness (e.g. pneumonia, urinary tract infection, mononucleosis)
  • use of antibiotics in past 2 weeks
  • follows vegan dietary regime
  • current smoker
  • typical alcohol consumption of 2 or more drinks per day
  • having undergone in vitro fertilization treatment
  • carrying more than one fetus
  • pregnancy-associated complications (i.e gestational diabetes, pre-eclampsia)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02124642

Contacts
Contact: Dorothy B Hausman, PhD 706-542-4871 dhausman@uga.edu
Contact: Hea Jin Park, PhD 706-542-5093 hjpark@uga.edu

Locations
United States, Georgia
Athens Regional Medical Center Midwifery Practice Not yet recruiting
Athens, Georgia, United States, 30606
Sponsors and Collaborators
University of Georgia
University of Florida
Emory University
Cornell University
Investigators
Principal Investigator: Lynn B Bailey, PhD University of Georgia
Study Director: Dorothy B Hausman, PhD University of Georgia
Study Director: Hea Jin Park, PhD University of Georgia
Study Director: Gail P A Kauwell, PhD, RDN University of Florida
Study Director: Marie A Caudill, PhD, RD Cornell University
Study Director: Alicia K Smith, PhD Emory Univeristy
  More Information

No publications provided

Responsible Party: Lynn B. Bailey, PhD, Department Head and Professor, University of Georgia
ClinicalTrials.gov Identifier: NCT02124642     History of Changes
Other Study ID Numbers: FASUPPPREG-2014
Study First Received: April 24, 2014
Last Updated: April 24, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Georgia:
Folate requirements
Pregnancy
Folic acid
DNA methylation
Folate biomarkers

Additional relevant MeSH terms:
Folic Acid
Vitamin B Complex
Growth Substances
Hematinics
Hematologic Agents
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Vitamins

ClinicalTrials.gov processed this record on November 20, 2014