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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dr. Peter Jones, University of Manitoba
ClinicalTrials.gov Identifier:
NCT01131832
First received: May 25, 2010
Last updated: January 30, 2015
Last verified: January 2015
  Purpose

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.


Condition Intervention Phase
Hyperlipidemia
Dietary Supplement: Plant sterol
Dietary Supplement: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: Genetic Basis for Heterogeneity in Response of Plasma Lipids to Plant Sterols

Resource links provided by NLM:


Further study details as provided by University of Manitoba:

Primary Outcome Measures:
  • Serum Lipids [ Time Frame: Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period ] [ Designated as safety issue: No ]
    Total Cholesterol, LDL-C, HDL-C, Triglycerides

  • Serum non-cholesterol sterols [ Time Frame: Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period ] [ Designated as safety issue: No ]
    Lathosterol,Lanosterol,Desmosterol,Sitosterol,Campesterol,Cholestanol,

  • Genotype via single nucleotide polymorphism analysis [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    SNP genotyping in genes related to cholesterol metabolism


Secondary Outcome Measures:
  • Cholesterol synthesis measurement by deuterium incorporation [ Time Frame: Endpoint (Day 27,28) of each experimental period ] [ Designated as safety issue: No ]
    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.

  • Change in cholesterol absorption due to plant sterol consumption [ Time Frame: Change in cholesterol absorption from control period (measured over days 24-28) to plant sterol period (days 24-28) ] [ Designated as safety issue: No ]
    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.


Enrollment: 71
Study Start Date: September 2010
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Plant sterol
Plant sterol supplementation, 2 grams per day of plant sterols in a margarine
Dietary Supplement: Plant sterol Dietary Supplement: Placebo

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01131832

Locations
United States, Maryland
USDA-ARS, Beltsville Human Nutrition Research Center
Beltsville, Maryland, United States, 20705
Canada, Manitoba
Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba
Winnipeg, Manitoba, Canada, R3T 6C5
Sponsors and Collaborators
University of Manitoba
Investigators
Principal Investigator: Peter J.H. Jones, PhD Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba
  More Information

Additional Information:
No publications provided

Responsible Party: Dr. Peter Jones, Professor, Food Science and Human Nutritional Sciences, University of Manitoba
ClinicalTrials.gov Identifier: NCT01131832     History of Changes
Other Study ID Numbers: B2007:073
Study First Received: May 25, 2010
Last Updated: January 30, 2015
Health Authority: Canada: Canadian Institutes of Health Research

Keywords provided by University of Manitoba:
Cholesterol, Plant sterols, Non-response, SNPs,

ClinicalTrials.gov processed this record on March 26, 2015