Study of the Relationships Between Apolipoprotein B-48 Kinetics and Expression of Genes That Regulate Intestinal Lipid Metabolism in Men With the Metabolic Syndrome (SMB48)

Metabolic Syndrome X Clinical Trial

Official title:

Study of the Relationships Between Apolipoprotein B-48 Kinetics and Expression of Genes That Regulate Intestinal Lipid Metabolism in Men With the Metabolic Syndrome.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01829945
• Other study ID #: INAF-129-05-02
• Status: Completed
• Phase: N/A
• First received: April 8, 2013
• Last updated: April 10, 2013
• Start date: October 2009
• Est. completion date: February 2011

Study information

• Verified date: April 2013
• Source: Laval University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Observational

Clinical Trial 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 show that overaccumulation of atherogenic triglyceride-rich lipoproteins (TRL) seen in insulin-resistant patients is partly due to increased production rate of intestinally derived apolipoproteinB-48-containing lipoproteins. This is of interest because substantial evidence exists indicating that elevated levels of intestinal lipoproteins are associated with increased CVD risk. However, as indicated in the body of this grant proposal, the underlying mechanisms that lead to intestinal overproduction of lipoproteins in insulin-resistant states are poorly understood.

The general objective of the proposed research is to investigate the mechanisms by which the metabolic syndrome affects apolipoproteinB-48 secretion in human. The primary hypothesis is that insulin resistance will be associated with higher levels of intestinal lipoproteins because of an increased secretion of these particles.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: February 2011
• Est. primary completion date: February 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

Subjects with metabolic syndrome:

• Men aged between 18-60 years

• Waist circumference >102

• HDL-cholesterol < 1.1 mmol/L

• Triglycerides > 1.7 mmol/L

• Fasting blood glucose >6.1 mmol/L

• Normal blood pressure (<130/85)

Controls:

• Men aged between 18-60 years

• Waist circumference >102

• 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

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Metabolic Syndrome X
• Syndrome

Locations

Country	Name	City	State
Canada	Institute of Nutrition and Functional Foods (INAF)	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Laval University	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in TRL apolipoproteinB-48 production rate.		Week 1	No
Secondary	Changes in duodenal expression of genes that regulate intestinal lipid absorption.	Genes that regulate intestinal lipid absorption that will be measured are Niemann-Pick C1-like-1 (NPC1L1), Adenosine triphosphate(ATP)-binding cassette transporters (ABCG5/8), Fatty Acid Binding Protein (FABP), Sterol Regulatory Element Binding Protein (SREBP)	Week 1	No
Secondary	Change in duodenal expression of genes that regulate intestinal lipid synthesis.	Genes that regulate intestinal lipid synthesis that will be measured are Acyl-Coenzyme A (CoA): diacylglycerol acyltransferase (DGAT), Acyl-CoA:cholesterol O-transferase 2 (ACAT2) and 3-hydroxy-methylglutaryl-CoA reductase (HMG CoA reductase).	Week 1	No
Secondary	Change in synthesis of apolipoproteinB-48 containing lipoproteins (Microsomal triglyceride transfer protein (MTP), apolipoproteinB-48).		Week 1	No