Mechanisms of Low Levels of Apolipoprotein B - Tabular View

Tracking Information

First Received Date ^ICMJE

May 25, 2000

Last Updated Date

January 25, 2008

Start Date ^ICMJE

August 1997

Primary Completion Date

June 2002 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Original Primary Outcome Measures ^ICMJE

Change History

Complete list of historical versions of study NCT00005565 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Original Secondary Outcome Measures ^ICMJE

Descriptive Information

Brief Title ^ICMJE

Mechanisms of Low Levels of Apolipoprotein B

Official Title ^ICMJE

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-44.4 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-44.4 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 Phase

N/A

Study Type ^ICMJE

Observational

Study Design ^ICMJE

Condition ^ICMJE

Cardiovascular Diseases
Heart Diseases
Hypobetalipoproteinemia

Intervention ^ICMJE

Study Arms / Comparison Groups

Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Enrollment ^ICMJE

Completion Date

June 2002

Primary Completion Date

June 2002 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

No eligibility criteria

Gender

Male

Ages

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Location Countries ^ICMJE

Administrative Information

NCT ID ^ICMJE

NCT00005565

Responsible Party

Study ID Numbers ^ICMJE

5114

Study Sponsor ^ICMJE

National Heart, Lung, and Blood Institute (NHLBI)

Collaborators ^ICMJE

Investigators ^ICMJE

Investigator:

Francine Welty

Beth Israel Deaconess Medical Center

Information Provided By

National Heart, Lung, and Blood Institute (NHLBI)

Verification Date

January 2008

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP