Characterization of the Pharmacokinetics of Oral Selenium Compounds in Humans Before and Following Supplementation

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00342966
First received: June 19, 2006
Last updated: July 24, 2010
Last verified: July 2010
  Purpose

The chemopreventive efficacy of Se was tested in a 10-year human intervention trial; total and lung cancer mortality, total cancer incidence, colorectal cancer and prostate cancer incidence decreased. This study is designed to compare, via stable isotope tracer studies the kinetics of inorganic and organic Se before and following two years of oral supplementation with L-selenomethionine, to measure forms of Se in the plasma (extracellular Se-dependent glutathione peroxidase [GSHPx], selenoprotein-P [SeP], albumin-bound Se [AlbSe] and nonprotein-bound low molecular weight [LMWSe] fractions), and to determine the effects of supplementation on the ecology of the hindgut microflora. The forms of Se were chosen to resemble the metabolism of the principal forms of Se in mixed American diets. Sodium selenite, an inorganic form, is metabolized by reduction to selenide which is then either used in the co-translational synthesis of SeCys in specific Se-containing proteins (e.g., glutathione peroxidases, diodinases, selenoproteins P and W), or is converted to methylated excretion products; in this sense it resembles the food form selenocysteine (SeCys) which is metabolized to the selenide level. Selenomethionine (SeMet), an organic form, is a major form of Se in many foods, particularly those of plan origin. In addition to being metabolized to selenide, SeMet also enters the metabolic protein pool by competing with the sulfur-containing amino acid, methionine. A study is proposed to assess the impact of selenium (Se) supplementation on its metabolism in humans.

A pilot study will be conducted to test recruitment strategies and sample collection, preparation and analysis and to assess the detectability of two stable isotopes given together. Four subjects will receive two 300 ug oral doses consisting of 150 ug of the stable isotope 76Se as selenite and 150 ug of the stable isotope 74Se as selenomethionine on study days one and twelve. Subjects will be followed for six weeks.

In the first pharmacokinetics tracer study (PK1), twenty-eight subjects will receive the same two labeled stable isotope doses, and will be followed for 4 months. In addition, two subjects who have been self-supplementing with 200 ug of Se as selenized yeast for two years will take part in PK1 to assess the sensitivity over time of the tracer assay in supplemented subjects. PK1 will be followed by a 2-yr supplementation period, in which all 28 subjects will receive daily doses of 200 ug of L0SeMet; subjects = metabolism is expected to approach a new steady state reflective of long-term supplementation. A second 4-month pharmacokinetic tracer study (PK2) will then be conducted while subjects remain on Se-supplementation with an extension of six monthly blood samples. Extensive sampling of plasma, urine, and feces during PK1 and PK2 will permit both the refinement of existing baseline models for selenite and selenomethionine metabolism in humans and the investigation of changes in metabolism arising from Se-supplementation. The study is designed to detect a difference of 0.75 standard deviation units in pre-versus post-supplementation rate parameters, assuming a two-sided test with an alpha level of 0.05 and a power of 0.80.

The non-absorbed portion of Se may favor portions of the normal colonic bacterial microflora that produce certain short-chain fatty acids that colon cells use for energy. To test this hypothesis, fecal specimens will be analyzed for short-chain fatty acids over the course of Se-supplementation. In addition, the sampling of buccal cell-Se and of toenail-Se on a quarterly basis over the course of the study and assay of thyroid hormone levels during the first year of the study will permit the investigation of possible changes in levels resulting from supplementation.


Condition
Cancer

Study Type: Observational
Official Title: Characterization of the Pharmacokinetics of Oral Selenium Compounds in Humans Before and Following Supplementation

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 34
Study Start Date: June 1999
Estimated Study Completion Date: July 2010
Detailed Description:

The chemopreventive efficacy of Se was tested in a 10-year human intervention trial; total and lung cancer mortality, total cancer incidence, colorectal cancer and prostate cancer incidence decreased. This study is designed to compare, via stable isotope tracer studies the kinetics of inorganic and organic Se before and following two years of oral supplementation with L-selenomethionine, to measure forms of Se in the plasma (extracellular Se-dependent glutathione peroxidase [GSHPx], selenoprotein-P [SeP], albumin-bound Se [AlbSe] and nonprotein-bound low molecular weight [LMWSe] fractions), and to determine the effects of supplementation on the ecology of the hindgut microflora. The forms of Se were chosen to resemble the metabolism of the principal forms of Se in mixed American diets. Sodium selenite, an inorganic form, is metabolized by reduction to selenide which is then either used in the co-translational synthesis of SeCys in specific Se-containing proteins (e.g., glutathione peroxidases, diodinases, selenoproteins P and W), or is converted to methylated excretion products; in this sense it resembles the food form selenocysteine (SeCys) which is metabolized to the selenide level. Selenomethionine (SeMet), an organic form, is a major form of Se in many foods, particularly those of plan origin. In addition to being metabolized to selenide, SeMet also enters the metabolic protein pool by competing with the sulfur-containing amino acid, methionine. A study is proposed to assess the impact of selenium (Se) supplementation on its metabolism in humans.

A pilot study will be conducted to test recruitment strategies and sample collection, preparation and analysis and to assess the detectability of two stable isotopes given together. Four subjects will receive two 300 ug oral doses consisting of 150 ug of the stable isotope 76Se as selenite and 150 ug of the stable isotope 74Se as selenomethionine on study days one and twelve. Subjects will be followed for six weeks.

In the first pharmacokinetics tracer study (PK1), twenty-eight subjects will receive the same two labeled stable isotope doses, and will be followed for 4 months. In addition, two subjects who have been self-supplementing with 200 ug of Se as selenized yeast for two years will take part in PK1 to assess the sensitivity over time of the tracer assay in supplemented subjects. PK1 will be followed by a 2-yr supplementation period, in which all 28 subjects will receive daily doses of 200 ug of L0SeMet; subjects = metabolism is expected to approach a new steady state reflective of long-term supplementation. A second 4-month pharmacokinetic tracer study (PK2) will then be conducted while subjects remain on Se-supplementation with an extension of six monthly blood samples. Extensive sampling of plasma, urine, and feces during PK1 and PK2 will permit both the refinement of existing baseline models for selenite and selenomethionine metabolism in humans and the investigation of changes in metabolism arising from Se-supplementation. The study is designed to detect a difference of 0.75 standard deviation units in pre-versus post-supplementation rate parameters, assuming a two-sided test with an alpha level of 0.05 and a power of 0.80.

The non-absorbed portion of Se may favor portions of the normal colonic bacterial microflora that produce certain short-chain fatty acids that colon cells use for energy. To test this hypothesis, fecal specimens will be analyzed for short-chain fatty acids over the course of Se-supplementation. In addition, the sampling of buccal cell-Se and of toenail-Se on a quarterly basis over the course of the study and assay of thyroid hormone levels during the first year of the study will permit the investigation of possible changes in levels resulting from supplementation.

  Eligibility

Ages Eligible for Study:   20 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Those subjects with normal physical examinations and Se plasma levels within the eligible range will be invited to participate in the study.

Men and women will be recruited according to the following eligibility criteria. Subjects must:

be between the ages of 20 and 60 years;

be in general good health as determined by a screening history and physical examination and laboratory tests with no history of gastrointestinal, hepatic, renal and/or hematologic diseases, cancer, coronary heart disease;

be within 20% from their ideal weight as described in the Metlife Height and Weight Tables (1993);

be consuming typical mixed diets;

give informed consent; and

be judged, based on a personal interview, as having a high probability of participating for the two-year eight month duration of the study.

EXCLUSION CRITERIA:

women: pregnant or lactating women; sexually active and not using contraceptives (e.g., condoms, oral contraceptives, diaphragm); planning to become pregnant during the experimental period; or post -menopausal (at least 6 months);

taking antibiotics on a regular basis;

have a history of taking Se supplements of more than 25 ug/d in the past year;

current smoker, or stopped smoking within the last 6 months;

on rigorous exercise or weight-reduction programs.

  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: NCT00342966

Locations
United States, Maryland
USDA
Beltsville, Maryland, United States
National Cancer Institute (NCI), 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00342966     History of Changes
Other Study ID Numbers: 999999032, OH99-C-N032
Study First Received: June 19, 2006
Last Updated: July 24, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Metabolism
Tracer Studies
Chemoprevention
Selenomethionine
Plasma Selenoproteins

ClinicalTrials.gov processed this record on September 22, 2014