Ignite Creation Date:
2024-05-05 @ 11:20 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005565
Status:
COMPLETED
Last Update Posted:
2016-07-29
First Post:
2000-05-25
Brief Title:
Mechanisms of Low Levels of Apolipoprotein B
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2008-01
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:
To determine mechanisms of low levels of apolipoprotein B
Detailed Description:
BACKGROUND
Elevated apoB levels are associated with an increased risk of coronary heart disease Hypobetalipoproteinemia HBLP is characterized by apoB levels less than the 5 percentile Dr Welty the principal investigator sequenced mutations for truncated forms of apoB-67 apoB-55 and apoB-444 which causes HBLP described a kindred from the Framingham Heart Study with HBLP due to an unidentified apoB gene mutation and purified apoB-67 containing lipoprotein particles Heterozygous apoB-67 subjects have one normal allele making apoB-100 therefore apoB levels would be predicted to be at least 50 percent of normal however they are 24 percent of normal Dr Welty has shown that these lower than expected levels result from decreased production of VLDL apoB-100 LDL apoB-100 and apoB-67 increased catabolism of VLDL apoB-100 and increased direct removal of apoB-67 from VLDL
DESIGN NARRATIVE
The first aim is to locate the apoB gene mutation in the Framingham kindred The second aim is to perform stable isotope studies in the apoB-55 and apoB-444 kindreds to determine if apoB metabolism for these shorter truncations is similar to that for apoB-67 In aim three apoB-100 synthesis is studied in heterozygous apoB-70 transgenic mice If it is 25-25 percent of normal litter mates the mechanism for this reduction in apoB-100 levels will be studied in hepatocytes isolated from the transgenic mice In specific aim 4 size and composition of VLDL are compared in apoB-67 subjects and controls to determine if larger size or compositional changes account for the faster catabolism of VLDL apoB-100 The study has been extended through June 2007
Elevated apoB levels are associated with an increased risk of coronary heart disease Hypobetalipoproteinemia HBLP is characterized by apoB levels less than the 5 percentile Dr Welty the principal investigator sequenced mutations for truncated forms of apoB-67 apoB-55 and apoB-444 which causes HBLP described a kindred from the Framingham Heart Study with HBLP due to an unidentified apoB gene mutation and purified apoB-67 containing lipoprotein particles Heterozygous apoB-67 subjects have one normal allele making apoB-100 therefore apoB levels would be predicted to be at least 50 percent of normal however they are 24 percent of normal Dr Welty has shown that these lower than expected levels result from decreased production of VLDL apoB-100 LDL apoB-100 and apoB-67 increased catabolism of VLDL apoB-100 and increased direct removal of apoB-67 from VLDL
DESIGN NARRATIVE
The first aim is to locate the apoB gene mutation in the Framingham kindred The second aim is to perform stable isotope studies in the apoB-55 and apoB-444 kindreds to determine if apoB metabolism for these shorter truncations is similar to that for apoB-67 In aim three apoB-100 synthesis is studied in heterozygous apoB-70 transgenic mice If it is 25-25 percent of normal litter mates the mechanism for this reduction in apoB-100 levels will be studied in hepatocytes isolated from the transgenic mice In specific aim 4 size and composition of VLDL are compared in apoB-67 subjects and controls to determine if larger size or compositional changes account for the faster catabolism of VLDL apoB-100 The study has been extended through June 2007
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01HL056895 | NIH | None | httpsreporternihgovquickSearchR01HL056895 |