Ignite Creation Date:
2024-05-05 @ 4:56 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00342966
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2006-06-19
Brief Title:
Characterization of the Pharmacokinetics of Oral Selenium Compounds in Humans Before and Following Supplementation
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Characterization of the Pharmacokinetics of Oral Selenium Compounds in Humans Before and Following Supplementation
Status:
COMPLETED
Status Verified Date:
2010-07-23
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 eg 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 075 standard deviation units in pre-versus post-supplementation rate parameters assuming a two-sided test with an alpha level of 005 and a power of 080
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
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 075 standard deviation units in pre-versus post-supplementation rate parameters assuming a two-sided test with an alpha level of 005 and a power of 080
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
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 eg 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 075 standard deviation units in pre-versus post-supplementation rate parameters assuming a two-sided test with an alpha level of 005 and a power of 080
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
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 075 standard deviation units in pre-versus post-supplementation rate parameters assuming a two-sided test with an alpha level of 005 and a power of 080
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| OH99-C-N032 | None | None | None |