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

May 25, 2010
January 30, 2015
September 2010
February 2012   (final data collection date for primary outcome measure)
  • 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
  • Serum Lipids [ Time Frame: Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental phase ] [ 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 phase ] [ 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
Complete list of historical versions of study NCT01131832 on ClinicalTrials.gov Archive Site
  • 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.
Haplotype analysis [ Time Frame: baseline ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Genetic Basis for Heterogeneity in Response of Plasma Lipids to Plant Sterols
Genetic Basis for Heterogeneity in Response of Plasma Lipids to Plant Sterols

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.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Hyperlipidemia
  • Dietary Supplement: Plant sterol
  • Dietary Supplement: Placebo
Experimental: Plant sterol
Plant sterol supplementation, 2 grams per day of plant sterols in a margarine
Interventions:
  • Dietary Supplement: Plant sterol
  • Dietary Supplement: Placebo
Mackay DS, Gebauer SK, Eck PK, Baer DJ, Jones PJ. Lathosterol-to-cholesterol ratio in serum predicts cholesterol-lowering response to plant sterol consumption in a dual-center, randomized, single-blind placebo-controlled trial. Am J Clin Nutr. 2015 Mar;101(3):432-9. doi: 10.3945/ajcn.114.095356. Epub 2015 Jan 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
71
February 2012
February 2012   (final data collection date for primary outcome measure)

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)
Both
30 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01131832
B2007:073
Not Provided
Dr. Peter Jones, University of Manitoba
University of Manitoba
Not Provided
Principal Investigator: Peter J.H. Jones, PhD Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba
University of Manitoba
January 2015

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