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Impact of High-dose Folic Acid Supplementation on Pathways Linked to DNA Formation

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified September 2014 by University of British Columbia
Sponsor:
Information provided by (Responsible Party):
University of British Columbia
ClinicalTrials.gov Identifier:
NCT01687127
First received: September 13, 2012
Last updated: September 25, 2014
Last verified: September 2014
  Purpose

Periconceptional supplementation with folic acid - the synthetic form of the B-vitamin folate - reduces the occurrence of adverse pregnancy outcomes such as spina bifida. The underlying biochemical mechanisms for how folic acid affects health outcomes however are unknown. The naturally occurring form 5-methyltetrahydrofolate (5-MTHF) is now available and discussed as an adequate substitute to folic acid. This study aims to determine the effect of folic acid compared to 5-MTHF on cellular mechanisms. Stable isotope tracer protocols will be used that allow determining the effect of folic acid on the dynamics of metabolic pathways in the human body.

Hypothesis: Supplementation with high-dose folic acid alters the turnover rate of folate dependent pathways in healthy humans; but 5-MTHF does not. Genetic variations in a key enzyme of the folate metabolism will aggravate the effect of folic acid on the metabolic pathways.


Condition Intervention
One-carbon Metabolism in Healthy Individuals
Dietary Supplement: Folic acid
Dietary Supplement: 5-methyltetrahydrofolate, calcium salt

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Metabolic Consequences of High-Dose Folic Acid Supplementation on Kinetics of 1-Carbon Metabolism

Resource links provided by NLM:


Further study details as provided by University of British Columbia:

Primary Outcome Measures:
  • Plateau enrichment of infused amino acid tracers and related metabolites to quantify turnover rates of folate dependent pathways [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: December 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Folic acid supplementation
Folic acid will be given orally in form of tablets. A supplement of 1 mg will be taken daily for 12 weeks. Thereafter, a supplement of 5 mg will be taken daily for 12 weeks (i.e., until Week 24). At baseline, Week 12, and Week 24, subjects will receive a 9-hour primed constant infusion of amino acids in saline solution for quantification of kinetics of one-carbon metabolism.
Dietary Supplement: Folic acid
Other Name: Pteroylmonoglutamic acid
Experimental: 5-MTHF supplementation
The calcium salt of 5-methyltetrahydrofolate (5-MTHF; Brand name "Metafolin") will be given orally in form of tablets. A supplement of 1 mg will be taken daily for 12 weeks. Thereafter, a supplement of 5 mg will be taken daily for 12 weeks (i.e., until Week 24). At baseline, Week 12, and Week 24, subjects will receive a 9-hour primed constant infusion of amino acids in saline solution for quantification of kinetics of one-carbon metabolism.
Dietary Supplement: 5-methyltetrahydrofolate, calcium salt
Other Names:
  • 5-MTHF
  • Metafolin (brand name)
  • Levomefolic acid

  Eligibility

Ages Eligible for Study:   20 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Generally healthy
  • Body mass index of between 19-24 kg/m2
  • Normal folate, vitamin B12, and B6 status

Exclusion Criteria:

  • Unable to swallow tablets
  • Unable to receive intravenous catheters
  • Use of vitamin supplements, amino acid or protein supplements for more than six months before study participation
  • Chronic consumption of a high-protein diet (e.g. Atkins Diet)
  • Medical conditions such as diabetes, asthma, cancer, cardiovascular disease, a history of neural tube defect (such as spina bifida) affected pregnancy, have had gastrointestinal surgery, abnormal kidney, thyroid function, or psychiatric illness, or any other chronic disease
  • Pregnancy or lactation
  • Smoking, use of recreational drugs, and/or consumption of more than one alcohol drink per day or more than seven per week.
  • Use of long-term prescription medication such as hormonal contraceptives, antidepressants, anticonvulsants, anticoagulants, or other chronic medication
  • Blood donation in the last three months prior to study start
  • Unable to provide informed consent, or unable to read and write English
  • Low compliance to intervention as determined by early steady-state or reduction in blood folate concentrations
  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: NCT01687127

Contacts
Contact: Theresa H Schroder, Dipl. 604-822-1250 schrod10@mail.ubc.ca
Contact: Yvonne Lamers, PhD 604-822-1490 yvonne.lamers@ubc.ca

Locations
Canada, British Columbia
Children's and Women's Health Centre of BC (incl. Sunny Hill), Child and Family Research Institute Not yet recruiting
Vancouver, British Columbia, Canada, V5Z 4H4
Contact: Theresa H Schroder, Dipl    604-822-1250    folate.study@ubc.ca   
Sub-Investigator: Jehannine C Austin, PhD         
Sub-Investigator: Amanda Skoll, MD, FRCSC         
Sponsors and Collaborators
University of British Columbia
Investigators
Principal Investigator: Yvonne Lamers, PhD University of British Columbia
  More Information

No publications provided

Responsible Party: University of British Columbia
ClinicalTrials.gov Identifier: NCT01687127     History of Changes
Other Study ID Numbers: H11-03009, CIHR Application Nr. 247226
Study First Received: September 13, 2012
Last Updated: September 25, 2014
Health Authority: Canada: Health Canada

Keywords provided by University of British Columbia:
folic acid
folate
5-methyltetrahydrofolate
supplements
women
one-carbon metabolism
methionine
DNA methylation
in vivo kinetics

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 25, 2014