Project Identifier: LBNL-79-106-H02
Project Title:
Metabolic & Genetic Origins of Lipoprotein Subclasses (see LBL-94-2-86 in 1994 database)
Principle Investigator:
Dr. Ronald M. Krauss
Project started in: 1979
Project Funding Information:
Project received funding in Fiscal Year 1995.
Project used human subjects in Fiscal Year 1995.
Funding Sources:
Project involves use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 7
Protocol/Subproject # 1
Protocol/Subproject Identifier: CRC Coll #1
IRB Review:
Type of Review: Full Board
Most Recent Approval: May 23, 1995
IRB Approval Number: 95-6-91
Number of Human Subjects in the Last Reporting Period for this Project: 25
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: Metabolic and Kinetic Basis of LDL Subclass Patterns and Effects of High-Carbohydrate Diet (collaborative study with Hellerstein of University of California, San Francisco)
OBJECTIVES
The objective of this study is to understand where the different density subclasses of lipoprotein come from and why their patterns differ among subjects with different risks for atherogenesis. With better understanding of the underlying principles, better diagnostic tools may be formed for the treatment of persons with lipoprotein disorders.
METHODOLOGY
Prospective subjects are classified by lipid subclass pattern; if they meet certain criteria, they are assigned to various dietary studies. Blood samples and tracer studies are used to assess subject's response to varying diet. Dietary studies, tracer studies, and blood drains take place at the collaborating site and are reviewed and approved by that Institutional Review Board.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
None.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
Human subject involvement is limited to the analysis of serum samples collected at another site; no additional risk to subjects is incurred by this analysis.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 19, 1994
IRB Approval Number: 94-8-108
Number of Human Subjects in the Last Reporting Period for this Project: 3
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: Cellular Origins of Apoprotein-Specific HDL Subclasses (Principal Investigator, T. Forte)
OBJECTIVES
The objective is to define the biochemical abnormalities in the Smith-Lemli-Opitz syndrome, a recessively inherited metabolic disorder associated with an inability of the affected subject to synthesize cholesterol. It is hoped that more accurate, specific biochemical characterization of the disorder will permit formulation of treatments and case management plans.
METHODOLOGY
Lipoproteins in the 1-2 ml samples are characterized via electron microscopy and gel electrophoresis.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
Human involvement is limited to use of 1-2 ml plasma samples collected by another researcher.
IRB Review:
Type of Review: Full Board
Most Recent Approval: February 17, 1995
IRB Approval Number: 95-2-114
Number of Human Subjects in the Last Reporting Period for this Project: 427
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: Genetic Analysis of Five HDL Subclasses in Family Sets (Principal Investigator, P. Williams)
To apply specific graphic and statistical analysis in an examination of high-density lipropotein subclass distributions in related individuals.
The data set under analysis was previously collected as part of the study of familial lipoprotein patterns. At the time of the data collection the statistical and mathematics ability to examine HDL subclasses did not exist. Data from the same population of 427 continues to be examined; no new subjects or additional risks are involved.
IRB Review:
Type of Review: Full Board
Most Recent Approval: February 17, 1995
IRB Approval Number: 95-2-98
Number of Human Subjects in the Last Reporting Period for this Project: 6
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: Blood Donations for Family Studies
OBJECTIVES
The objective of this study is to examine the inheritance of lipid and lipoprotein levels and the physical properties, as well as chemical composition, of human plasma proteins in order to obtain insights on how to control heart diseases.
METHODOLOGY
Up to 80cc of blood are drawn from subjects via venipuncture. Additionally, a medical interview is conducted with each subject in which demographic information, family/personal health history, dietary, exercise and smoking habits, etc., are requested.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
The risks are those common to venipuncture (bruising, slight risk of infection).
IRB Review:
Type of Review: Full Board
Most Recent Approval: February 17, 1995
IRB Approval Number: 95-2-98
Number of Human Subjects in the Last Reporting Period for this Project: 500
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: Blood Donations for Lipoprotein Research
OBJECTIVES
The objective of this study is to obtain blood for isolation of lipoproteins and plasma proteins, and as a source of lipids for lipoprotein interaction studies. Since certain lipoproteins have been indicated as predisposing individuals to arteriosclerosis and heart disease, this study aims to obtain insights on how to control such diseases.
METHODOLOGY
Not more than a unit of blood (500cc) will be drawn from donors by venipuncture. Blood bank criteria will be used in determining frequency of donor use. Some donors may be asked to fast overnight prior to blood withdrawal.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
Risks are those common to venipuncture (bruising, mild risk of infection).
IRB Review:
Type of Review: Full Board
Most Recent Approval: April 17, 1995
IRB Approval Number: 95-4-85
Number of Human Subjects in the Last Reporting Period for this Project: 10
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: Postdrandial Chylomicron Clearance After an Intravenous Fat Load
OBJECTIVES
The objective of this study is to examine the mechanisms underlying changes in lipoprotein and chylomicron levels. This will aid in the formation of better diagnostic and treatment tools for conditions involving atherogenesis, the development of arterial plaques.
METHODOLOGY
Control subjects and individuals with specific blood plasma lipoprotein profiles will have their chylomicron clearance rate determined by consuming a high-fat meal after an infusion of synthetically produced chylomicron particles. Blood is then drawn by common clinical venipuncture and analyzed.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
Intravenous administration of a solution of artificial chylomicron particles. A standardized high-fat milkshake will be taken orally.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
Subjects will include normal controls and those with any of three inherited blood lipid abnormalities. Subjects on lipid lowering medication will be asked to abstain for six weeks prior, at no significant risk to the patient due to the short duration. All will be injected with a solution of laboratory-created chylomicron particles and given a high-fat milkshake to consume; the clearance rate will be determined by sequentially sampling blood over the following 90 minutes. Both the chylomicrons infusion and venipuncture carry a remote risk of infection.
IRB Review:
Type of Review: Full Board
Most Recent Approval: February 17, 1995
IRB Approval Number: 95-2-100
Number of Human Subjects in the Last Reporting Period for this Project: 20
(Reporting periods vary.)
Type of Human Subjects Involvement:
TITLE: Effects of a High-Fat Meal on the Lipid Composition of Lipoprotein Subfractions in Pattern A and Pattern B Subjects
OBJECTIVES
The objective of this study is to investigate possible differences in the postprandial lipemia of subjects with Type A and Type B lipoprotein profiles and, in turn, examine that relationship with respect to the incidence of coronary arterial disease (CAD). Type B subjects, characterized by the predominance of small, dense low-density lipoprotein particles, increased triglyceride levels, and reductions in high-density lipoprotein have a three-fold increased risk of myocardial infarction, but little is known of the role of different responses following eating. This information will aid in the formation of better diagnostic tools and treatment regimes for people with increased CAD risk.
METHODOLOGY
Subjects in this study receive a high-fat meal (milkshake) followed by a collection of blood by routine venipuncture. The results of the blood lipid analyses are then evaluated in light of the subject's clinical and familial history of CAD.
IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES
A standardized high-fat milkshake will be taken orally.
INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS
Subjects will have blood drawn for the Type A/B screening. On the day of the study, the subjects, who have fasted 12 hours, have a blood sample taken, then consume a high-fat milkshake. Four hours afterwards, blood will be drawn and a second milkshake consumed. Blood will be drawn again four hours later. The blood drawing process, via venipuncture, carries a small risk of bruising and a remote risk of infection.