Folic Acid Supplementation in Women of Child Bearing Age (FASUPP)

July 1, 2016 updated by: Lynn B. Bailey, PhD, University of Georgia

Effect of Obesity and Folic Acid Supplementation on Gene-specific DNA Methylation in Women of Reproductive Age

The objective of this study is to identify genes whose expression is potentially modifiable due to changes in folate intake and help delineate mechanisms accounting for the variability in individual response to folic acid supplementation. The study will be conducted in normal weight and obese women of childbearing age, supplemented for 8 weeks with 800 mcg/day folic acid.

It is hypothesized that (1) a change in folate status, induced by the supplementation, will influence the DNA methylation of specific genes and (2) the DNA methylation response to folic acid supplementation may differ between the normal weight and the obese women of childbearing age.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study will be conducted in two phases. An initial screening study will be performed to determine folate status, MTHFR677 genotype and body composition of potential participants of the intervention study. Both folate status and MTHFR677 genotype are known independent predictors of response to folic acid supplementation. Blood samples will be collected, after an overnight fast, for determination of serum folate concentration and for MTHFR677 genotyping. Body composition and 24-hr dietary recalls will also be conducted during the screening visit.

The second phase is an eight week supplementation trial with 800 mcg/day folic acid. Screened individuals determined to have a serum folate < 30 nmol/L (< 50th percentile of NHANES 1999-2004) and of the CC or CT genotype (for MTHFR677) will be eligible for inclusion in the supplementation trial. Participants will be instructed to avoid dietary supplements, fortified ready-to-eat cereals, and other high folate content foods during intervention. Blood samples will be collected, after an overnight fast, at baseline and after 4 and 8 weeks of supplementation for determination of primary (DNA methylation profile) and secondary (nutritional, metabolic and health status biomarkers) outcome measures.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Georgia
      • Athens, Georgia, United States, 30602
        • University of Georgia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Screening Phase:
  • Female 18-40 yr
  • Body Mass index 18.5 to 24.9 or > 30 kg/m2
  • Intervention Study:
  • Serum folate < 30 nmol/L
  • MTHFR677CC or MTHFR677CT genotype

Exclusion Criteria:

  • Currently pregnant, pregnancy within past 12 months
  • Greater than 2 previous pregnancies
  • Use of prescription drugs other than oral contraceptives
  • Chronic disease (diabetes, hypertension,epilepsy,cancer, kidney disease, CVD)
  • Acute illness (pneumonia, urinary tract infection, mononucleosis)
  • Use of antibiotics in past 30 days
  • Current smoker
  • Use of dietary supplements including multivitamins in past 30 days
  • Habitual consumption of fortified ready-to-eat cereals
  • Significant weight change in past 12 months
  • Typical alcohol consumption of 2 or more drinks per day
  • INTERVENTION: all above plus serum folate > 30 nmol/L; MTHFR677TT genotype

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Folic Acid Normal Weight
Folic acid, tablet, 800 mcg, daily, eight weeks. Normal Weight individuals, each will serve as her own control.
Participants will be instructed to consume 2 tablets per day, a total of 800 micrograms folic acid. To facilitate compliance, participants will be instructed in the use of a compliance calendar and will receive frequent telephone and 'text' reminders from project staff. Additionally, compliance will be determined by return pill count.
Experimental: Folic acid Obese
Folic acid, tablet, 800 mcg, daily, eight weeks. Obese individuals, each will serve as her own control.
Participants will be instructed to consume 2 tablets per day, a total of 800 micrograms folic acid. To facilitate compliance, participants will be instructed in the use of a compliance calendar and will receive frequent telephone and 'text' reminders from project staff. Additionally, compliance will be determined by return pill count.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cell-type-specific DNA methylation
Time Frame: Baseline, 4 weeks and 8 weeks
Change in DNA methylation in response to 4 or 8 weeks supplementation with 800 mcg/day of folic acid will be determined in DNA isolated from specific white blood cell types. Microarray analysis will be used to assess changes in multiple methylation sites within regulatory pathways for folate metabolism and/or development. Each subject will serve as her own control.
Baseline, 4 weeks and 8 weeks
Gene-specific DNA methylation
Time Frame: Baseline, 4 weeks and 8 weeks
Change in DNA methylation in response to 4 or 8 weeks supplementation with 800 mcg/day of folic acid will be determined in DNA isolated from whole blood . Microarray analysis will be used to assess changes in multiple methylation sites of specific genes within regulatory pathways for folate metabolism and/or development. Each subject will serve as her own control.
Baseline, 4 weeks and 8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum folate
Time Frame: Baseline, 4 weeks and 8 weeks
Change in serum folate concentrations in response to 4 or 8 weeks supplementation with 800 mcg/day of folic acid will be determined by microbiological assay using Lactobacillus rhamnosus. Each subject will serve as her own control.
Baseline, 4 weeks and 8 weeks
Red Blood Cell (RBC) Folate
Time Frame: Baseline, 4 weeks and 8 weeks
Change in red blood cell (RBC) folate in response to 4 or 8 weeks supplementation with 800 mcg/day of folic acid will be determined by microbiological assay using Lactobacillus rhamnosus.
Baseline, 4 weeks and 8 weeks
Body Composition
Time Frame: Baseline and 8 weeks
Body composition in terms of fat mass (g), lean mass (g) and % body fat will be determined using the BODPOD instrument and verified by dual-energy X-ray absorptiometry (DXA). The DXA analysis will also provide an indication of regional fat distribution, and total bone area, bone mineral content and bone density.
Baseline and 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Lynn B Bailey, PhD, University of Georgia
  • Study Director: Dorothy Hausman, PhD, University of Georgia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (Actual)

August 1, 2015

Study Completion (Actual)

June 1, 2016

Study Registration Dates

First Submitted

April 19, 2013

First Submitted That Met QC Criteria

April 23, 2013

First Posted (Estimate)

April 26, 2013

Study Record Updates

Last Update Posted (Estimate)

July 4, 2016

Last Update Submitted That Met QC Criteria

July 1, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Obesity

Clinical Trials on Folic acid

Subscribe