One-carbon Metabolism in Healthy IndividualsNCT01687127
Impact of High-dose Folic Acid Supplementation on Pathways Linked to DNA Formation
A study testing Folic acid and 5-methyltetrahydrofolate, calcium salt in people with One-carbon Metabolism in Healthy Individuals, run by University of British Columbia at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 20 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- One-carbon Metabolism in Healthy Individuals
- What is being tested?
- Folic acid and 5-methyltetrahydrofolate, calcium salt
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteCanada
- Study dates
- 1 Jan 2024to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Generally healthy
- Body mass index of between 19-24 kg/m2
- Normal folate, vitamin B12, and B6 status
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site
Children's and Women's Health Centre of BC (incl. Sunny Hill), Child and Family Research Institute
Vancouver, British Columbia, V5Z 4H4
Yvonne Lamers, PhD, 604-827-1776, yvonne.lamers@ubc.ca
Amy McMahon, PhD, 604-822-1250, amy.mcmahon@ubc.ca
About this study
Official title: Metabolic Consequences of High-Dose Folic Acid Supplementation on Kinetics of 1-Carbon Metabolism
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.
- Being tested
- Folic acid, 5-methyltetrahydrofolate, calcium salt
- Keywords
- folic acid, folate, 5-methyltetrahydrofolate, supplements, women, one-carbon metabolism, methionine, DNA methylation, in vivo kinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Folic acidDietary supplement
Also called Pteroylmonoglutamic acid
Supplement
5-methyltetrahydrofolate, calcium saltDietary supplement
Also called 5-MTHF, Metafolin (brand name), Levomefolic acid
Supplement
| Study group | Role | What they receive |
|---|---|---|
| Folic acid supplementation | Experimental | 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. Receives: Dietary Supplement: Folic acid |
| 5-MTHF supplementation | Experimental | 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. Receives: Dietary Supplement: 5-methyltetrahydrofolate, calcium salt |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plateau enrichment of infused amino acid tracers and related metabolites to quantify turnover rates of folate dependent pathways
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2012 (estimated)
- Study start1 Jan 2024 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for One-carbon Metabolism in Healthy IndividualsStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yvonne Lamers, University of British Columbia
- Investigators
- Yvonne Lamers, PhD, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01687127
- Sponsor's protocol ID
- H11-03009
- Other IDs
- CIHR Application Nr. 247226
- Status last verified
- Aug 2023
- First submitted
- 13 Sep 2012
- Last updated
- 15 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Consequences of High-Dose Folic Acid Supplementation on Kinetics of 1-Carbon Metabolism
- ClinicalTrials.gov ID
- NCT01687127
- Acronym / sponsor ID
- H11-03009
- Keywords
- folic acid, folate, 5-methyltetrahydrofolate, supplements, women, one-carbon metabolism, methionine, DNA methylation
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- 1 Jan 2024 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 18 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Folic acid supplementation | Experimental | Dietary Supplement: Folic acidFolic 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. |
| 5-MTHF supplementation | Experimental | Dietary Supplement: 5-methyltetrahydrofolate, calcium saltThe 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. |
Who may qualify
- Ages
- 20 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Generally healthy
- Body mass index of between 19-24 kg/m2
- Normal folate, vitamin B12, and B6 status
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Folic acidAlso: Pteroylmonoglutamic acidSupplement | Dietary supplement | Folic acid supplementation |
| 5-methyltetrahydrofolate, calcium saltAlso: 5-MTHF, Metafolin (brand name), Levomefolic acidSupplement | Dietary supplement | 5-MTHF supplementation |
Primary outcome
Plateau enrichment of infused amino acid tracers and related metabolites to quantify turnover rates of folate dependent pathways
Time frame: 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2023.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yvonne Lamers, PhD principal investigator
University of British Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Folic acid and 5-methyltetrahydrofolate, calcium salt in people with One-carbon Metabolism in Healthy Individuals, run by University of British Columbia at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 15 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yvonne Lamers, PhD (604-827-1776, yvonne.lamers@ubc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plateau enrichment of infused amino acid tracers and related metabolites to quantify turnover rates of folate dependent pathways (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2023.