Clinical trial NCT01806142: Effects of Medium-Chain Triglycerides on Chylomicron Secretion and Expression of Genes That Regulate Intestinal Lipid Metabolism in Men With Dyslipidemia Associated With the Metabolic Syndrome
Official title: Effects of Medium-Chain Triglycerides on Chylomicron Secretion and Expression of Genes That Regulate Intestinal Lipid Metabolism in Men With Dyslipidemia Associated With the Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome X
Lead sponsor: Laval University
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2013-03-07
Enrollment: 28
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: Several lines of evidence indicate that a significant proportion of cardiovascular disease (CVD) events are attributable to the presence of a cluster of metabolic abnormalities and perturbations, defined as the metabolic syndrome. It has been estimated that approximately 25% of the North American adult population is living with the metabolic syndrome. Recent studies from the investigators group show that overaccumulation of atherogenic triglyceride-rich lipoproteins (TRL) seen in insulin-resistant patients is partly due to increased production rate of intestinally derived apolipoprotein (apo) B-48-containing lipoproteins. This is of interest because substantial evidence exists indicating that elevated levels of intestinal lipoproteins are associated with increased CVD risk. In this regard, there is some evidence that medium-chain triglycerides (MCTs) may beneficially modify lipoprotein metabolism in hypertriglyceridemic patients. However, as emphasized in the body of this grant proposal, the specific impact of MCTs on the intestinal lipoprotein secretion and on expression of genes that regulate intestinal lipid absorption and chylomicron synthesis has not yet been investigated in humans.

The general objective of the proposed research is to investigate the mechanisms by which MCTs beneficially modify intestinal lipoprotein metabolism in patients with the metabolic syndrome. The primary hypothesis is that MCT supplementation will decrease plasma levels of intestinal lipoproteins by reducing secretion of these particles.


Eligibility criteria: Inclusion Criteria:

* Men aged between 18-60 years
* Waist circumference \> 102 cm
* HDL-cholesterol \< 1.1 mmol/L
* Triglycerides \> 1.7 mmol/L
* Fasting blood glucose \> 6.1 mmol/L
* Normal blood pressure (\<130/85)

Exclusion Criteria:

* Women
* Men \< 18 or \> 60 years
* Smokers (\> 1 cigarette/day)
* Body weight variation \> 10% during the last 6 months prior to the study baseline
* Subjects with a previous history of cardiovascular disease
* Subjects with type 2 diabetes
* Subjects with a monogenic dyslipidemia
* Subjects on hypertension medications or medications known to affect lipoprotein metabolism or the integrity of gastrointestinal mucosa
* Subjects with endocrine or gastrointestinal disorders
* History of alcohol or drug abuse within the past 2 years
* Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study.

Primary outcomes:
measure: Change in TRL apolipoprotein B48 (apoB-48) production rate.
timeFrame: At week 4 and week 10 (at the end of the two 4-weeks supplementation).
Secondary outcomes:
measure: Changes in duodenal expression of genes that regulate intestinal lipid absorption.
timeFrame: At week 4 and week 10 (at the end of the two 4-weeks supplementation).
measure: Changes in duodenal expression of genes that regulate intestinal lipid synthesis.
timeFrame: At week 4 and week 10 (at the end of the two 4-weeks supplementation).
measure: Change in synthesis of apoB-48 containing lipoproteins (Microsomal triglyceride transfer protein (MTP), apoB-48).
timeFrame: At week 4 and week 10 (at the end of the two 4-weeks supplementation).
Other outcomes:
Locations:
city: Quebec
country: Canada
facility: Institute of Nutrition and Functional Foods (INAF)
Study officials:
affiliation: Laval University
name: Patrick Couture, MD,FRCP,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tremblay AJ, Lamarche B, Labonte ME, Lepine MC, Lemelin V, Couture P. Dietary medium-chain triglyceride supplementation has no effect on apolipoprotein B-48 and apolipoprotein B-100 kinetics in insulin-resistant men. Am J Clin Nutr. 2014 Jan;99(1):54-61. doi: 10.3945/ajcn.113.068767. Epub 2013 Oct 30.