Mechanisms of Low Levels of Apolipoprotein B

This study has been completed.
Sponsor:
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00005565
First received: May 25, 2000
Last updated: January 25, 2008
Last verified: January 2008
  Purpose

To determine mechanisms of low levels of apolipoprotein B.


Condition
Cardiovascular Diseases
Heart Diseases
Hypobetalipoproteinemia

Study Type: Observational

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Study Start Date: August 1997
Study Completion Date: June 2002
Primary Completion Date: June 2002 (Final data collection date for primary outcome measure)
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.

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

No eligibility criteria

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005565

Sponsors and Collaborators
Investigators
Investigator: Francine Welty Beth Israel Deaconess Medical Center
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00005565     History of Changes
Other Study ID Numbers: 5114
Study First Received: May 25, 2000
Last Updated: January 25, 2008
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Cardiovascular Diseases
Heart Diseases
Hypobetalipoproteinemias
Hypolipoproteinemias
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on April 23, 2014