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

May 5, 2017 updated by: Dr. Peter J. H. Jones, University of Manitoba
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

71

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3T 6C5
        • Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba
  • United States
    • Maryland
      • Beltsville, Maryland, United States, 20705
        • USDA-ARS, Beltsville Human Nutrition Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Plant sterol
Plant sterol supplementation, 2 grams per day of plant sterols in a margarine
Dietary supplement: Placebo
Dietary supplement: Plant sterol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum Lipids
Time Frame: Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period
Total Cholesterol, LDL-C, HDL-C, Triglycerides
Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period
Serum non-cholesterol sterols
Time Frame: Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period
Lathosterol,Lanosterol,Desmosterol,Sitosterol,Campesterol,Cholestanol,
Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period
Genotype via single nucleotide polymorphism analysis
Time Frame: Baseline
SNP genotyping in genes related to cholesterol metabolism
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cholesterol synthesis measurement by deuterium incorporation
Time Frame: Endpoint (Day 27,28) of each experimental period
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
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)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Manitoba

Investigators

  • Principal Investigator: Peter J.H. Jones, PhD, Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2010

Primary Completion (Actual)

February 1, 2012

Study Completion (Actual)

February 1, 2012

Study Registration Dates

First Submitted

May 25, 2010

First Submitted That Met QC Criteria

May 25, 2010

First Posted (Estimate)

May 27, 2010

Study Record Updates

Last Update Posted (Actual)

May 9, 2017

Last Update Submitted That Met QC Criteria

May 5, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B2007:073

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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