Genetic Basis for Heterogeneity in Response of Plasma Lipids to Plant Sterols

Hyperlipidemia Clinical Trial

Official title:

Genetic Basis for Heterogeneity in Response of Plasma Lipids to Plant Sterols

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01131832
• Other study ID #: B2007:073
• Status: Completed
• Phase: Phase 4
• First received: May 25, 2010
• Last updated: May 5, 2017
• Start date: September 2010
• Est. completion date: February 2012

Study information

• Verified date: May 2017
• Source: University of Manitoba
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The substantial range of individual responsiveness to plant sterols has important ramifications. Marked differences across individuals in particular aspects of the cholesterol metabolic pathway must alter the impact of plant sterol consumption. As such, a pronounced need exists to understand the genetic and metabolic factors that explain the substantial degree of heterogeneity in response of lipid concentrations to plant sterols across individuals. The primary focus of this trial is to delineate the impact of differing cholesterol synthesis levels on response of LDL-C and other plasma lipids to plant sterol consumption. Participants pre-identified as high or low endogenous cholesterol synthesizers, according to their screening level of lathosterol to cholesterol ratios, will be given PS or a placebo containing margarine to consume under supervision for 4 weeks in a crossover design. The trial will characterize the responsiveness of the participants' total, LDL, and HDL cholesterol, as well as triacylglycerol (TG) concentrations, to plant sterol consumption. This research will determine if cholesterol synthesis phenotype predicts the responsiveness of lipids to plant sterol consumption. Variations in candidate genes involved in cholesterol metabolism will also be investigated in order to find associations with both cholesterol metabolism phenotypes and responsiveness of lipids to plant sterols. The output of this research will be to advance the knowledge of which genetic factors influence the degree of cardiovascular benefit derived from plant sterols through lipid lowering.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

Inclusion Criteria:

• fasting serum LDL cholesterol >3.0 mmol/L

• high or low lathosterol to cholesterol ratio

Exclusion Criteria:

• smoking

• use of lipid lowering therapy

• documented cardiovascular/atherosclerotic disease

• inflammatory disease

• diabetes

• uncontrolled hypertension

• kidney disease

• liver disease

• other systemic diseases

• cancer

• chronic alcohol consumption (> 2 servings/day)

Related Conditions & MeSH terms

• Hyperlipidemia
• Hyperlipidemias

Intervention

Dietary Supplement:
• Plant sterol

• Placebo

Locations

Country	Name	City	State
Canada	Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba	Winnipeg	Manitoba
United States	USDA-ARS, Beltsville Human Nutrition Research Center	Beltsville	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
University of Manitoba

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum Lipids	Total Cholesterol, LDL-C, HDL-C, Triglycerides	Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period
Primary	Serum non-cholesterol sterols	Lathosterol,Lanosterol,Desmosterol,Sitosterol,Campesterol,Cholestanol,	Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period
Primary	Genotype via single nucleotide polymorphism analysis	SNP genotyping in genes related to cholesterol metabolism	Baseline
Secondary	Cholesterol synthesis measurement by deuterium incorporation	Cholesterol biosynthesis will be determined as the rate of incorporation of deuterium from body water into red blood cell membrane free cholesterol over a 24 hour period (day 27 to day 28 of each period). The change in deuterium enrichment within red blood cell free cholesterol will be determined as an index of synthesis, the fractional synthesis rate (FSR) of cholesterol.	Endpoint (Day 27,28) of each experimental period
Secondary	Change in cholesterol absorption due to plant sterol consumption	Ninety-six hours before the end of each period, participants will ingest 65 mg [3, 4-13C]-cholesterol. The 13C-cholesterol will be dissolved in 5 g of warmed margarine, and consumed on a slice of bread. A fasted blood sample will be taken at baseline on day 24 prior to isotope administration, as well as fasting samples on days 25, 26, 27 and 28 to monitor enrichment levels of 13C-cholesterol in plasma total cholesterol. The area under the curve of 13C-cholesterol from 0-96 hours (days 24-28) at the end of the control period will be compared to the same area under the curve at the end of the plant sterol period to determine the change in cholesterol absorption due to plant sterol consumption.	Change in cholesterol absorption from control period (measured over days 24-28) to plant sterol period (days 24-28)

External Links

•   Richardson Centre for Functional Foods and Nutraceuticals