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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
University of Florida
Emory University
Information provided by (Responsible Party):
Lynn B. Bailey, PhD, University of Georgia
ClinicalTrials.gov Identifier:
NCT01841658
First received: April 19, 2013
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention
Obesity
Dietary Supplement: Folic acid

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effect of Obesity and Folic Acid Supplementation on Gene-specific DNA Methylation in Women of Reproductive Age

Resource links provided by NLM:


Further study details as provided by University of Georgia:

Primary Outcome Measures:
  • Cell-type-specific DNA methylation [ Time Frame: Baseline, 4 weeks and 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Gene-specific DNA methylation [ Time Frame: Baseline, 4 weeks and 8 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Serum folate [ Time Frame: Baseline, 4 weeks and 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Red Blood Cell (RBC) Folate [ Time Frame: Baseline, 4 weeks and 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Body Composition [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 200
Study Start Date: April 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Folic Acid Normal Weight
Folic acid, tablet, 800 mcg, daily, eight weeks. Normal Weight individuals, each will serve as her own control.
Dietary Supplement: Folic acid
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.
Dietary Supplement: Folic acid
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.

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.

  Eligibility

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

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
  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: NCT01841658

Locations
United States, Georgia
University of Georgia
Athens, Georgia, United States, 30602
Sponsors and Collaborators
University of Georgia
University of Florida
Emory University
Investigators
Principal Investigator: Lynn B Bailey, PhD University of Georgia
Study Director: Dorothy Hausman, PhD University of Georgia
  More Information

No publications provided

Responsible Party: Lynn B. Bailey, PhD, Department Head and Professor, University of Georgia
ClinicalTrials.gov Identifier: NCT01841658     History of Changes
Other Study ID Numbers: UGA_FASUPPLEMENT_EPIGEN
Study First Received: April 19, 2013
Last Updated: April 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Georgia:
Folate Status
Folate Biomarkers

Additional relevant MeSH terms:
Obesity
Body Weight
Nutrition Disorders
Overnutrition
Overweight
Signs and Symptoms
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 October 20, 2014