Clinical trial NCT01131832: Genetic Basis for Heterogeneity in Response of Plasma Lipids to Plant Sterols
Official title: Genetic Basis for Heterogeneity in Response of Plasma Lipids to Plant Sterols
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hyperlipidemia
Keywords: Cholesterol, Plant sterols, Non-response, SNPs,
Lead sponsor: University of Manitoba
Sponsor class: OTHER
First posted: 2010-05-27
Enrollment: 71
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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)

Primary outcomes:
measure: Serum Lipids
timeFrame: Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period
measure: Serum non-cholesterol sterols
timeFrame: Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period
measure: Genotype via single nucleotide polymorphism analysis
timeFrame: Baseline
Secondary outcomes:
measure: Cholesterol synthesis measurement by deuterium incorporation
timeFrame: Endpoint (Day 27,28) of each experimental period
measure: Change in cholesterol absorption due to plant sterol consumption
timeFrame: Change in cholesterol absorption from control period (measured over days 24-28) to plant sterol period (days 24-28)
Other outcomes:
Locations:
city: Beltsville
country: United States
facility: USDA-ARS, Beltsville Human Nutrition Research Center
state: Maryland
city: Winnipeg
country: Canada
facility: Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba
state: Manitoba
Study officials:
affiliation: Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba
name: Peter J.H. Jones, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.