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

NCT01131832 | Completed Phase 4

• 1 other identifier: B2007:073
• Study Type: interventional
• Target: 71
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Hyperlipidemia

Keywords

Cholesterol, Plant sterols, Non-response, SNPs,

Outcome Measures

Primary Outcomes (3)

• Serum Lipids

  Total Cholesterol, LDL-C, HDL-C, Triglycerides

  Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period

• Serum non-cholesterol sterols

  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

  SNP genotyping in genes related to cholesterol metabolism

  Baseline

Secondary Outcomes (2)

• Cholesterol synthesis measurement by deuterium incorporation

  Endpoint (Day 27,28) of each experimental period

• 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)

Study Arms (1)

Plant sterol

EXPERIMENTAL

Plant sterol supplementation, 2 grams per day of plant sterols in a margarine

Dietary Supplement: Plant sterol; Dietary Supplement: Placebo

Interventions

Plant sterol DIETARY_SUPPLEMENT

Plant sterol

Placebo DIETARY_SUPPLEMENT

Plant sterol

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• fasting serum LDL cholesterol \>3.0 mmol/L
• high or low lathosterol to cholesterol ratio

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Manitoba: lead

Study Sites (2)

USDA-ARS, Beltsville Human Nutrition Research Center

Beltsville, Maryland, 20705, United States

Location

Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba

Winnipeg, Manitoba, R3T 6C5, Canada

Location

Related Publications (2)

• MacKay DS, Eck PK, Gebauer SK, Baer DJ, Jones PJ. CYP7A1-rs3808607 and APOE isoform associate with LDL cholesterol lowering after plant sterol consumption in a randomized clinical trial. Am J Clin Nutr. 2015 Oct;102(4):951-7. doi: 10.3945/ajcn.115.109231. Epub 2015 Sep 2.

  PMID: 26333513 DERIVED

• 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.

  PMID: 25733626 DERIVED

MeSH Terms

Conditions

Hyperlipidemias

Interventions

Phytosterols

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sterols; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Membrane Lipids; Lipids; Phytochemicals; Biological Factors

Study Officials

• Peter J.H. Jones, PhD

  Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Food Science and Human Nutritional Sciences

Study Record Dates

• First Submitted: May 25, 2010
• First Posted: May 27, 2010
• Study Start: September 1, 2010
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: May 9, 2017

Record last verified: 2017-05

Locations

US (1); CA (1)