Vitamin B6 Deficiency Clinical Trial
Official title:
Vitamin B6 Dependence of One-Carbon Metabolism
Marginal vitamin B6 deficiency, which occurs commonly worldwide, leads to a cellular deficiency of the coenzyme pyridoxal phosphate (PLP). PLP is a coenzyme in several phases of one carbon (1C) metabolism, which is the array of reactions in which one carbon units are acquired and used in reactions including nucleotide synthesis, regeneration of methionine (Met) from homocysteine (Hcy), and methylation of many biological compounds. 1C metabolism is linked to the transsulfuration pathway in which Hcy undergoes PLP-dependent catabolism leading to cysteine, whose availability governs the formation of the antioxidant glutathione. Nutritional or genetic conditions that impair 1C metabolism are associated with elevation in plasma Hcy concentration and increased risk of vascular disease. It is believed that the metabolic effects of vitamin B6 deficiency will be most pronounced following protein intake when the vitamin B6-dependent pathways of amino acid metabolism experience the greatest substrate load. The human subjects protocols of this study consist of two distinct phases intended to extend our understanding of basic human 1C metabolism and the effects of marginal vitamin B6 deficiency under postprandial conditions. Phase 1 will investigate the effects of vitamin B6 nutrition on the PLP-dependent generation of 1C units by the glycine cleavage system and on the synthesis of glutathione. Phase 2 will investigate the dependence of methionine metabolism on vitamin B6 nutritional status, with particular emphasis on the recycling of Hcy to Met. Each phase of this study will involve 14 healthy, nutritionally adequate, young adults (7 male, 7 female) who will undergo metabolite profiling and kinetic analysis using intravenously infused stable isotopic tracers performed both before and after a ~4-week period of dietary vitamin B6 restriction. Subjects will be assigned to either Phase 1 or Phase 2, which will be identical in design except for the tracers and analytical methods used. We hypothesize that vitamin B6 deficiency will yield reduction in postprandial rates of homocysteine remethylation, generation of 1C units from glycine, and synthesis of glutathione. The results of this study will aid in assessing the consequences of nutritional and genetic variables affecting human metabolism and will further our understanding of the relationships between vitamin B6 nutrition and disease.
If you volunteer for this study, you will come to the General Clinical Research Center
(GCRC) at Shands Hospital for a screening visit. There approximately 27.5 mL of blood (5 1/2
teaspoons) will be taken from a vein in your arm. This will be used for tests to determine
whether you are receiving adequate amounts of vitamin B6 and other vitamins, to analyze a
part of the genetic information in certain blood cells that relates to how your body
processes some nutrients, and to confirm your general health. If the vitamin B6 content of
your blood is higher than the range needed for this study, which sometimes occurs from
eating fortified foods, you might be asked to give another blood sample (2 teaspoons) after
several weeks to have the screening test repeated. You will also be asked questions about
your health and a detailed assessment of your regular diet will be carried out. Your general
health will be confirmed by taking a medical history, physical exam, and standard blood
tests including liver, kidney, bone marrow function, cholesterol and urine analysis. To take
part in this study, you must be in good health and in adequate nutritional status for
vitamin B6 and other vitamins.
Because of risks to a developing fetus from inadequate vitamin B6 intake, a pregnancy test
will be conducted with females three times during the study (during the screening visit and
before each hospital admission) and women who participate in this study should use
protection to prevent pregnancy during the study; if you become pregnant you will be
released from the study.
Once you have completed all screening procedures you will be asked to eat meals prepared by
the GCRC for 2 days, you will then participate in the procedure to test how effectively
vitamin B6 functions in helping your body use certain amino acids. This will involve giving
you a solution of certain amino acids by a vein in your arm over the course of 9 hours.
On the evening before this procedure, you will report to the GCRC at approximately 8:00 p.m.
You will spend the night at the GCRC and will not be allowed to eat after 9:00 p.m. On the
following morning, you will not be given breakfast. You will have an intravenous catheter
placed into a vein in each arm, one for blood samples to be taken throughout the day, and
one for the amino acid solution to be given. You will also be asked to breath (one breath)
through a straw into a glass tube at different times, while the amino acid solution is being
given. Before starting the amino acid solution, a blood sample (about 7 teaspoons) will be
taken from a vein in one arm. Then the solution containing amino acids and nucleotides will
be pumped slowly into your blood over the next 9-hour period. You will not be allowed to eat
normal foods during this 9-hour period. However, you will be given a liquid nutritional
formula to drink each hour during the day (starting after the first blood sample is taken).
Approximately 14 blood samples (9 mL, less than 2 teaspoons each) and 8 breath samples will
be taken from you while you receive the amino acid solution. In addition, at 6 times during
the day you will be asked to lie quietly for 10 minutes while breathing into a special,
clear hood that will measure your metabolic rate (the rate at which your body uses energy).
You will remain at the GCRC for the entire 9-hour period, although you will be able to do
limited activities (TV and reading). At the end of the 9-hour period, you will be able to go
home and resume your activities. The following day you will resume eating meals prepared by
the GCRC. While at the GCRC on days 3 and 4 after this procedure, you will be asked to give
two more blood samples, one in the morning and one in the evening, and on day 5 you will be
asked to give one blood sample in the morning (2 teaspoons each).
The day after you are discharged from the GCRC, you will be asked to eat, for a period of
approximately 4 weeks, a diet containing reduced amounts of vitamin B6 and limit the amount
of caffeine (in coffee, tea, and carbonated drinks) you drink to one to two per day. Twice
each day during this approximately 4 week period you will come to the General Clinical
Research Center (GCRC) at Shands Hospital where you will eat your breakfast and evening
meals. Also, you will be weighed once daily and have your heart rate, respirations and blood
pressure monitored twice weekly. You will be given a sack lunch to be consumed wherever you
choose. To be sure that you are getting adequate amounts of all nutrients except the vitamin
being studied, you will be given a pill containing a vitamin and mineral supplement each
day. Once each week (when you come into the GCRC to eat breakfast), you will have two
teaspoons of blood taken from a vein in your arm to allow monitoring of your vitamin B6
status.
After finishing approximately 4 weeks on this diet, you will participate again in the
procedure to test how effectively vitamin B6 functions in helping your body use certain
amino acids. Again, this will involve giving you a solution of certain amino acids by a vein
in your arm over the course of 9 hours. As before, you will report to the GCRC at
approximately 8:00 p.m. on the evening before the procedure. You will spend the night at the
GCRC and will not be allowed to eat after 9:00 p.m. The exact same procedures will be
carried out as in the first admission.
A few days prior to the second admission, while you are on the GCRC receiving your diet, you
will have the same general health blood and urine tests collected as you had done before the
first admission.
When the amino acid solution has been completely given, approximately 9 hours, you will be
able to go home and resume your activities. You will be asked to return to the GCRC to give
blood samples on days 3, 4, and 5 after this procedure just as you did after the first
admission. You will then be finished with the study. You will be given a 30 day supply of
vitamin and mineral supplements to be taken daily to be sure that your body gets adequate
amounts of vitamin B6 and other nutrients.
After the laboratory analysis of blood samples from this study has been completed, if you
agree, some of the samples will be kept in frozen storage for possible future analysis of
nutrients or genetic information related to how your body processes nutrients. Please refer
to the Addendum for Blood Storage and Future Testing attached.
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Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT01128244 -
Vitamin B6 Effects for Women Taking Birth Control Pills
|
Phase 2/Phase 3 |