The objective of this study is to utilize information on associations between genetic predisposition pertaining to multiple single nucleotide polymorphisms (SNPs) and the degree of responsiveness of low-density lipoprotein cholesterol (LDL-C) lowering to plant sterols (PS). The predictive potential of SNPs associated with PS responsiveness will be evaluated using a randomized human intervention trial examining responsiveness of lowering blood LDL-C levels to PS intervention.
On average plant sterol (PS) consumption of 2-3 grams a day leads to a \~10% decrease in low-density lipoprotein cholesterol (LDL-C). However, inter-individual response to PS consumption varies, with some individuals showing low or no reductions in LDL-C levels, while some even showing an increase in levels. Determining factors that predict the direction of response of LDL-C to PS would be helpful in identifying individuals who should consume PS and individuals who should seek another method of treating hypercholesterolemia. The objective of this research proposal is to test the a priori predictive potential of a combination of three single nucleotide polymorphisms (SNPs), i.e., genosets, previously associated with response to PS in a post-hoc manner. A clinical trial with a priori recruitment of participants based on genoset which will test LDL-C response to PS consumption using a randomized, double blind, placebo controlled crossover design is proposed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
43
2.0g/day of plant sterols incorporated into margarine to be consumed for 28 days
Identical margarine without additional plant sterols to be consumed for 28 days
Department of Human Nutritional sciences, University of Manitoba
Winnipeg, Manitoba, Canada
Change in fasting low-density lipoprotein cholesterol (LDL-C) levels between placebo and treatment endpoints (in a crossover design)
Time frame: Endpoint (Days 28,29) of each treatment period
Change in fasting total cholesterol (TC) levels between placebo and treatment endpoints (in a crossover design)
Time frame: Endpoint (Days 28,29) of each treatment period
Change in fasting high-density lipoprotein cholesterol levels between placebo and treatment endpoints
Time frame: Endpoint (Days 28,29) of each treatment period
Change in fasting triglyceride (TG) levels between placebo and treatment endpoints (in a crossover design)
Time frame: Endpoint (Days 28,29) of each treatment period
Change in body weight between placebo and treatment endpoints (in a crossover design)
Time frame: Endpoint (Days 28,29) of each treatment period
Change in body mass index (BMI) between placebo and treatment endpoints (in a crossover design)
Time frame: Endpoint (Days 28,29) of each treatment period
Change in waist circumference between placebo and treatment endpoints (in a crossover design)
Time frame: Endpoint (Days 28,29) of each treatment period
Change in blood pressure between placebo and treatment endpoints (in a crossover design)
Time frame: Endpoint (Days 28,29) of each treatment period
Change in arterial stiffness-Pulse wave velocity between placebo and treatment endpoints (in a crossover design)
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Pulse wave velocity will be determined using an automated oscillometric measurement device (Mobil-O-Graph, IEM, Stolberg, Germany).
Time frame: Endpoint (Days 28,29) of each treatment period
Change in arterial stiffness-augmentation index between placebo and treatment endpoints (in a crossover design)
Augmentation index will be determined using an automated oscillometric measurement device (Mobil-O-Graph, IEM, Stolberg, Germany).
Time frame: Endpoint (Days 28,29) of each treatment period
Change in fasting glucose levels between placebo and treatment endpoints (in a crossover design)
Time frame: Endpoint (Days 28,29) of each treatment period
Change in blood sterols and sterol precursors (non-cholesterol sterols) levels between placebo and treatment endpoints (in a crossover design)
Time frame: Endpoint (Days 28,29) of each treatment period
Change in fractional cholesterol synthesis between placebo and treatment endpoints (in a crossover design)
A fasted blood sample will be taken on day 28 of each study period prior to deuterium oxide administration, as well as fasting samples on day 29. The change in deuterium enrichment within red blood cell (RBC) free cholesterol we be determined as an index of synthesis over days 28 and 29.
Time frame: Endpoint (Day 28,29) of each treatment period