Vitamin B6 DeficiencyPhase 2/3NCT01128244
Vitamin B6 Effects for Women Taking Birth Control Pills
A Phase 2/3 study testing Vitamin B6 and Infusion of labeled serine, methionine and leucine in people with Vitamin B6 Deficiency, run by University of Florida at 1 site in United States.
Trial summary
Chronically inadequate B6 nutritional status is associated with aberrant one-carbon (1C) metabolism and health. Plasma pyridoxal phosphate (PLP) >30 nmol/L often has been considered to be the cutoff indicative of nutritional adequacy, with 20-30 nmol/L considered marginal deficiency; however, the current Recommended… Read more about this study
- Who is it for?
- Ages 20 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Vitamin B6 Deficiency
- What is being tested?
- Vitamin B6 and Infusion of labeled serine, methionine and leucine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2010to Jun 2014
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- healthy female subjects
- normal screening labs
- normal body weight
- nonpregnant
- Plasma PLP<30nmol/L
Who cannot join
- history of gastrointestinal surgery
- chronic disease
- vitamin supplementation
- high protein diet
- progesterone
- no smoking
Show all 9Show fewer
- chronic drug use
- alcoholism
- no vitamin supplementation
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Florida Clinical Research Center
Gainesville, Florida, 32610
About this study
Official title: Vitamin B6 Effects on One-Carbon Metabolism
Chronically inadequate B6 nutritional status is associated with aberrant one-carbon (1C) metabolism and health. Plasma pyridoxal phosphate (PLP) >30 nmol/L often has been considered to be the cutoff indicative of nutritional adequacy, with 20-30 nmol/L considered marginal deficiency; however, the current Recommended Dietary Allowance (RDA) value was based on a more conservative cutoff of 20 nmol/L plasma PLP. As shown by in the investigators preliminary data, biochemical perturbations occur when humans have marginal B6 deficiency consistent with plasma PLP of 20-30 nmol/L. A prospective study also showed that plasma PLP <23.3 nmol/L is associated with 1.8-times higher risk of recurrent venous thromboembolism than those with PLP >23.3 nmol/L. The mechanism by which low B6 intake is associated with risk of vascular disease is not known. Since B6-deficiency has little tendency to raise fasting plasma total homocysteine (tHcy) but yields an elevated tHcy response following a methionine load, low B6 nutriture may lead to repeated transient mild hyperhomocysteinemia following meal consumption. Several reports of associations between elevated plasma C-reactive protein (CRP) and low B6 status have raised the hypothesis that systemic inflammation is prone to occur during B6 deficiency or contributes to low B6 status. The investigators previously found that healthy humans in low B6 status caused by dietary restriction exhibited normal plasma CRP levels. The investigators also postulate that oxidative stress associated with low B6 status, coupled with impaired glutathione synthesis, contributes to such risk. These questions indicate the need for a more thorough understanding of the metabolic changes occurring in low B6 status from marginal B6 intake and from drug interactions such as in women using oral contraceptives.
Read the detailed description
Potential subjects will undergo a prescreening visit to meet the inclusion criteria, have a history, physical exam and routine labs drawn. The labs will verify the nutritional eligibility of folate, vitamin B12 and vitamin B6. If the inclusion criteria is met then the following will take place.
The subjects will come to the University of Florida (UF) Clinical and Translational Science Institute (CTSI) Clinical Research Center (CRC) for a 9 hour infusion (with stable isotope labeled serine, methionine and leucine) twice during the research study. Once at the start of the study and again at day 29. Blood samples will be taken for metabolite analysis. The infusion of nonradioactive, stable isotope labeled amino acids allows determination of the rate of metabolic reactions in one-carbon metabolism. The results from all subjects' blood analyses will provide us with information about rates of several parts of metabolism and vitamin B6 status.
During the 2-days prior to the infusion a controlled diet will be required. The subjects will be fed at the CTSI CRC. Dietary calculations and formulations will be conducted by using Minnesota Nutrition Data Systems software. Subjects will come to the CRC twice per day where they will meet with staff, consume morning and evening meals, and will be provided a sack lunch and snacks (including weekends). Protein intake will be kept constant.
After the first infusion, all subjects will consume their self-selected usual diets for 28 days along with a commercial B6 supplement providing 10 mg/day. Weekly measurement of blood will be used to verify compliance. All subjects will then consume a 2-day controlled diet at the UF CRC to normalize protein intake, followed by an infusion procedure identical to the first.
During the 4-week supplementation period, all subjects will come to the CRC weekly for weighing, blood samples, and consultation with staff. Careful screening, close monitoring and education of subjects, along with weekly monitoring of blood levels, all contribute to a high degree of compliance.
- Conditions
- Vitamin B6 Deficiency
- Being tested
- Vitamin B6, Infusion of labeled serine, methionine and leucine
- Keywords
- oral contraceptives, Vitamin B6, birth control pills, amino acids, Vitamin B6 deficiency, Vitamin B6 deficiency in women on oral contraceptives
- Medical subject headings
- Vitamin B 6 Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin B6Dietary supplement
Also called pyridoxine HCl supplement, USP pyridoxine HCL
Subjects will receive vitamin B6 supplementation.
Infusion of labeled serine, methionine and leucineProcedure or surgery
Subjects will be given an infusion of the stable isotope labeled amino acids, serine, methionine and leucine prior to vitamin B6 supplementation and after 28 days of B6 treatment. In addition, they will receive a special diet 2 days prior to the infusion and will have weekly weight, blood, and visits to the clinic.
| Study group | Role | What they receive |
|---|---|---|
| Vitamin B6 Effects in OC Users | Experimental | All subjects will be given an infusion of labeled serine, methionine and leucine prior to vitamin B6 supplementation and after 28 days of treatment. In addition, they will receive a special diet 2 days prior to the infusion and will have weekly weight, blood, and visits to the clinic.
The results from analysis of vitamin B6 and these amino acids in blood will provide us with specific measurements of the rates of two aspects of metabolism (Primary Outcomes 1 and 2) and specific measurements of vitamin B6 nutritional status (Primary Outcomes 3 and 4). Receives: Dietary Supplement: Vitamin B6; Procedure: Infusion of labeled serine, methionine and leucine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Remethylation of Homocysteine
Data from analysis of serine, methionine and leucine in the timed blood samples of all subjects will provide a measurement of the metabolic rate of total remethylation of homocysteine before and after vitamin B6 supplementation.
Measured: Blood samples will be taken prior to infusion and at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7.5, and 9h. Infusions will be conducted at baseline and after 28 days
Flux of Homocysteine Remethylation From Serine-derived Carbon
Data from analysis of serine, methionine and leucine in the timed blood samples of all subjects will provide a measurement of the metabolic rate of homocysteine remethylation from serine-derived carbon before and after vitamin B6 supplementation. These flux values may be slightly higher than flux of total homocysteine remethylation in Outcome Measure 1 because of the small contribution of methionine salvage to the flux measured in Outcome Measure 2.
Measured: Blood samples will be taken prior to infusion and at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7.5, and 9h. Infusions will be conducted at baseline and after 28 days
Fasting Plasma Pyridoxal Phosphate Concentration
For all subjects, the concentration of plasma pyridoxal phosphate in fasting blood samples taken before and after the supplementation period will provide a direct measure of vitamin B6 nutritional status.
Measured: Fasting blood samples will be taken at baseline and after 28 days of vitamin B6 supplementation.
Fasting Plasma Cystathionine Concentration
For all subjects, the concentration of plasma cystathionine in fasting blood samples taken before and after the supplementation period will provide a functional measure of vitamin B6 nutritional status.
Measured: Fasting blood samples will be taken at baseline and after 28 days of vitamin B6 supplementation.
Secondary outcomes (1)
Plasma 3-hydroxykynurenine Concentration
For all subjects, analysis of blood samples before and after vitamin B6 supplementation will allow evaluation of discriminating biomarkers using targeted metabolite profile analysis of one-carbon metabolism and tryptophan catabolism constituents. Also, we will conduct exploratory evaluation and potential identification of new biomarkers using metabolomics analysis on subjects before and after vitamin B6 supplementation.
Measured: April, 2010 - June, 2014
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2010 (estimated)
- Study startApr 2010
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Vitamin B6 DeficiencyStudies of the same condition, open and under way.
- More trials run by University of FloridaThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jesse Gregory, PhD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01128244
- Sponsor's protocol ID
- 2RO1DKO72398-05
- Status last verified
- Dec 2016
- First submitted
- 20 May 2010
- Last updated
- 7 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Gregory JF, DeRatt BN, Rios-Avila L, Ralat M, Stacpoole PW. Vitamin B6 nutritional status and cellular availability of pyridoxal 5'-phosphate govern the function of the transsulfuration pathway's canonical reactions and hydrogen sulfide production via side reactions. Biochimie. 2016 Jul;126:21-6. doi: 10.1016/j.biochi.2015.12.020. Epub 2016 Jan 4.
PubMed 26765812Rios-Avila L, Coats B, Ralat M, Chi YY, Midttun O, Ueland PM, Stacpoole PW, Gregory JF 3rd. Pyridoxine supplementation does not alter in vivo kinetics of one-carbon metabolism but modifies patterns of one-carbon and tryptophan metabolites in vitamin B-6-insufficient oral contraceptive users. Am J Clin Nutr. 2015 Sep;102(3):616-25. doi: 10.3945/ajcn.115.113159. Epub 2015 Jul 22.
PubMed 26201817Rios-Avila L, Coats B, Chi YY, Midttun O, Ueland PM, Stacpoole PW, Gregory JF 3rd. Metabolite profile analysis reveals association of vitamin B-6 with metabolites related to one-carbon metabolism and tryptophan catabolism but not with biomarkers of inflammation in oral contraceptive users and reveals the effects of oral contraceptives on these processes. J Nutr. 2015 Jan;145(1):87-95. doi: 10.3945/jn.114.201095. Epub 2014 Nov 19.
PubMed 25527663
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin B6 Effects on One-Carbon Metabolism
- ClinicalTrials.gov ID
- NCT01128244
- Acronym / sponsor ID
- 2RO1DKO72398-05
- Conditions
- Vitamin B6 Deficiency
- Keywords
- oral contraceptives, Vitamin B6, birth control pills, amino acids, Vitamin B6 deficiency, Vitamin B6 deficiency in women on oral contraceptives
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Apr 2010
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 21 May 2010 (estimated)
- Results
- Posted 17 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronically inadequate B6 nutritional status is associated with aberrant one-carbon (1C) metabolism and health. Plasma pyridoxal phosphate (PLP) >30 nmol/L often has been considered to be the cutoff indicative of nutritional adequacy, with 20-30 nmol/L considered marginal deficiency; however, the current Recommended Dietary Allowance (RDA) value was based on a more conservative cutoff of 20 nmol/L plasma PLP. As shown by in the investigators preliminary data, biochemical perturbations occur when humans have marginal B6 deficiency consistent with plasma PLP of 20-30 nmol/L. A prospective study also showed that plasma PLP <23.3 nmol/L is associated with 1.8-times higher risk of recurrent venous thromboembolism than those with PLP >23.3 nmol/L. The mechanism by which low B6 intake is associated with risk of vascular disease is not known. Since B6-deficiency has little tendency to raise fasting plasma total homocysteine (tHcy) but yields an elevated tHcy response following a methionine load, low B6 nutriture may lead to repeated transient mild hyperhomocysteinemia following meal consumption. Several reports of associations between elevated plasma C-reactive protein (CRP) and low B6 status have raised the hypothesis that systemic inflammation is prone to occur during B6 deficiency or contributes to low B6 status. The investigators previously found that healthy humans in low B6 status caused by dietary restriction exhibited normal plasma CRP levels. The investigators also postulate that oxidative stress associated with low B6 status, coupled with impaired glutathione synthesis, contributes to such risk. These questions indicate the need for a more thorough understanding of the metabolic changes occurring in low B6 status from marginal B6 intake and from drug interactions such as in women using oral contraceptives.
Detailed description
Potential subjects will undergo a prescreening visit to meet the inclusion criteria, have a history, physical exam and routine labs drawn. The labs will verify the nutritional eligibility of folate, vitamin B12 and vitamin B6. If the inclusion criteria is met then the following will take place.
The subjects will come to the University of Florida (UF) Clinical and Translational Science Institute (CTSI) Clinical Research Center (CRC) for a 9 hour infusion (with stable isotope labeled serine, methionine and leucine) twice during the research study. Once at the start of the study and again at day 29. Blood samples will be taken for metabolite analysis. The infusion of nonradioactive, stable isotope labeled amino acids allows determination of the rate of metabolic reactions in one-carbon metabolism. The results from all subjects' blood analyses will provide us with information about rates of several parts of metabolism and vitamin B6 status.
During the 2-days prior to the infusion a controlled diet will be required. The subjects will be fed at the CTSI CRC. Dietary calculations and formulations will be conducted by using Minnesota Nutrition Data Systems software. Subjects will come to the CRC twice per day where they will meet with staff, consume morning and evening meals, and will be provided a sack lunch and snacks (including weekends). Protein intake will be kept constant.
After the first infusion, all subjects will consume their self-selected usual diets for 28 days along with a commercial B6 supplement providing 10 mg/day. Weekly measurement of blood will be used to verify compliance. All subjects will then consume a 2-day controlled diet at the UF CRC to normalize protein intake, followed by an infusion procedure identical to the first.
During the 4-week supplementation period, all subjects will come to the CRC weekly for weighing, blood samples, and consultation with staff. Careful screening, close monitoring and education of subjects, along with weekly monitoring of blood levels, all contribute to a high degree of compliance.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vitamin B6 Effects in OC Users | Experimental | Dietary Supplement: Vitamin B6, Procedure: Infusion of labeled serine, methionine and leucineAll subjects will be given an infusion of labeled serine, methionine and leucine prior to vitamin B6 supplementation and after 28 days of treatment. In addition, they will receive a special diet 2 days prior to the infusion and will have weekly weight, blood, and visits to the clinic. The results from analysis of vitamin B6 and these amino acids in blood will provide us with specific measurements of the rates of two aspects of metabolism (Primary Outcomes 1 and 2) and specific measurements of vitamin B6 nutritional status (Primary Outcomes 3 and 4). |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- healthy female subjects
- normal screening labs
- normal body weight
- nonpregnant
- Plasma PLP<30nmol/L
Key exclusion criteria (9 listed)
- history of gastrointestinal surgery
- chronic disease
- vitamin supplementation
- high protein diet
- progesterone
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 |
|---|---|---|
| Vitamin B6Also: pyridoxine HCl supplement, USP pyridoxine HCLSubjects will receive vitamin B6 supplementation. | Dietary supplement | Vitamin B6 Effects in OC Users |
| Infusion of labeled serine, methionine and leucineSubjects will be given an infusion of the stable isotope labeled amino acids, serine, methionine and leucine prior to vitamin B6 supplementation and after 28 days of B6 treatment. In addition, they will receive a special diet 2 days prior to the infusion and will have weekly weight, blood, and visits to the clinic. | Procedure or surgery | Vitamin B6 Effects in OC Users |
Primary outcome
Total Remethylation of Homocysteine
Time frame: Blood samples will be taken prior to infusion and at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7.5, and 9h. Infusions will be conducted at baseline and after 28 days
Data from analysis of serine, methionine and leucine in the timed blood samples of all subjects will provide a measurement of the metabolic rate of total remethylation of homocysteine before and after vitamin B6 supplementation.
Flux of Homocysteine Remethylation From Serine-derived Carbon
Time frame: Blood samples will be taken prior to infusion and at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7.5, and 9h. Infusions will be conducted at baseline and after 28 days
Data from analysis of serine, methionine and leucine in the timed blood samples of all subjects will provide a measurement of the metabolic rate of homocysteine remethylation from serine-derived carbon before and after vitamin B6 supplementation. These flux values may be slightly higher than flux of total homocysteine remethylation in Outcome Measure 1 because of the small contribution of methionine salvage to the flux measured in Outcome Measure 2.
Fasting Plasma Pyridoxal Phosphate Concentration
Time frame: Fasting blood samples will be taken at baseline and after 28 days of vitamin B6 supplementation.
For all subjects, the concentration of plasma pyridoxal phosphate in fasting blood samples taken before and after the supplementation period will provide a direct measure of vitamin B6 nutritional status.
Fasting Plasma Cystathionine Concentration
Time frame: Fasting blood samples will be taken at baseline and after 28 days of vitamin B6 supplementation.
For all subjects, the concentration of plasma cystathionine in fasting blood samples taken before and after the supplementation period will provide a functional measure of vitamin B6 nutritional status.
1 secondary outcome
Plasma 3-hydroxykynurenine Concentration
Time frame: April, 2010 - June, 2014
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26765812Gregory JF, DeRatt BN, Rios-Avila L, Ralat M, Stacpoole PW. Vitamin B6 nutritional status and cellular availability of pyridoxal 5'-phosphate govern the function of the transsulfuration pathway's canonical reactions and hydrogen sulfide production via side reactions. Biochimie. 2016 Jul;126:21-6. doi: 10.1016/j.biochi.2015.12.020. Epub 2016 Jan 4.
- Derived from this study: PubMed 26201817Rios-Avila L, Coats B, Ralat M, Chi YY, Midttun O, Ueland PM, Stacpoole PW, Gregory JF 3rd. Pyridoxine supplementation does not alter in vivo kinetics of one-carbon metabolism but modifies patterns of one-carbon and tryptophan metabolites in vitamin B-6-insufficient oral contraceptive users. Am J Clin Nutr. 2015 Sep;102(3):616-25. doi: 10.3945/ajcn.115.113159. Epub 2015 Jul 22.
- Derived from this study: PubMed 25527663Rios-Avila L, Coats B, Chi YY, Midttun O, Ueland PM, Stacpoole PW, Gregory JF 3rd. Metabolite profile analysis reveals association of vitamin B-6 with metabolites related to one-carbon metabolism and tryptophan catabolism but not with biomarkers of inflammation in oral contraceptive users and reveals the effects of oral contraceptives on these processes. J Nutr. 2015 Jan;145(1):87-95. doi: 10.3945/jn.114.201095. Epub 2014 Nov 19.
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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. This study is not recruiting at the moment.
Jesse Gregory, PhD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Vitamin B6 and Infusion of labeled serine, methionine and leucine in people with Vitamin B6 Deficiency, run by University of Florida at 1 site in United States.
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 5 inclusion and 9 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: finished, as of the sponsor's last update on 7 Feb 2017. 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 United States. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Remethylation of Homocysteine (time frame: Blood samples will be taken prior to infusion and at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7.5, and 9h. Infusions will be conducted at baseline and after 28 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01128244, which also lists 3 linked publications.
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 7 Feb 2017.