Effects of Polyunsaturated Fatty Acids on Intestinal Lipid Metabolism in Insulin-resistant Men (PUFA)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2013 by Laval University
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Patrick Couture, Laval University
ClinicalTrials.gov Identifier:
NCT01934543
First received: August 30, 2013
Last updated: September 3, 2013
Last verified: August 2013
  Purpose

The overaccumulation of apolipoprotein (apo)B-48-containing lipoproteins of intestinal origin observed in patients with insulin-resistance is now thought to be attributable to both elevated intestinal production and reduced clearance of these lipoproteins. Substantial evidence exists indicating that elevated plasma levels of these lipoproteins are associated with increased cardiovascular disease (CVD) risk. Therefore, reduction of atherogenic plasma TRL levels of intestinal origin appears to be crucial to improve CVD risk associated with insulin-resistance. In this regard, there is some evidence that the clinical recommendation to replace dietary saturated fatty acids (SFAs) by n-6 polyunsaturated fatty acids (PUFAs) reduces CVD risk in the general population. Although the beneficial impact of n-6 PUFAs on CVD risk has been related primarily to favorable changes in plasma LDL-cholesterol levels, recent data suggest that chronic n-6 PUFA consumption may also exert beneficial effects on CVD risk by reducing postprandial lipemia. The impact of substituting SFAs by n-6 PUFAs on postprandial lipid response may be of even greater significance in dyslipidemic patients with insulin-resistance among whom intestinal triglyceride-rich lipoproteins (TRLs) represent a large proportion of the atherogenic lipoproteins. The general objective of the proposed research is to investigate how dietary n-6 PUFAs in place of SFAs modify intestinal lipoprotein metabolism in men with dyslipidemia associated with insulin-resistance. The investigators hypothesize that the intestinal secretion of apoB-48-containing lipoproteins will be lower following a diet rich in n-6 PUFAs than after consuming a diet rich in SFAs. The investigators also hypothesize that substitution of SFAs by n-6 PUFAs will be associated with significant alterations in expression of key genes and proteins involved in intestinal lipoprotein metabolism.


Condition Intervention
Metabolic Syndrome
Other: Polyunsaturated fatty acids diet
Other: Saturated fatty acids diet

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Differential Effects of Saturated and Polyunsaturated Fatty Acids on Chylomicron Secretion and Expression of Key Genes and Proteins That Regulate Intestinal Lipid Metabolism in Men With Dyslipidemia Associated With Insulin-resistance

Resource links provided by NLM:


Further study details as provided by Laval University:

Primary Outcome Measures:
  • Change in TRL apolipoprotein B48 (apoB-48) production rate. [ Time Frame: At week 4 and week 12 (at the end of the two 4-weeks diets). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in duodenal expression of genes that regulate intestinal lipid absorption. [ Time Frame: At week 4 and week 12 (at the end of the two 4-weeks diets). ] [ Designated as safety issue: No ]
    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-1c).

  • Changes in duodenal expression of genes that regulate intestinal lipid synthesis. [ Time Frame: At week 4 and week 12 (at the end of the two 4-weeks diets). ] [ Designated as safety issue: No ]
    Genes that regulate intestinal lipid synthesis that will be measured are Acyl-Coenzyme A(CoA):diacylglycerol acyltransferase (DGAT), Acyl-CoA:cholesterol O-acyltransferase 2 (ACAT2) and 3-hydroxy-methylglutaryl-CoA reductase (HMG CoA reductase).

  • Change in synthesis of apoB-48 containing lipoproteins (Microsomal triglyceride transfer protein (MTP), apoB-48). [ Time Frame: At week 4 and week 12 (at the end of the two 4-weeks diets). ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: January 2014
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Polyunsaturated fatty acids diet
During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0% from carbohydrates; 35.0% from fat: 6.0% from saturated fat; 14.4% from monounsaturated fat; 12.6% from n-6 polyunsaturated fat).
Other: Polyunsaturated fatty acids diet
During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0% from carbohydrates; 35.0% from fat: 6.0% from saturated fat; 14.4% from monounsaturated fat; 12.6% from n-6 polyunsaturated fat).
Experimental: Saturated fatty acids diet
During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0% from carbohydrates; 35.0% from fat: 13.4% from saturated fat; 15.3% from monounsaturated fat; 4.0% from n-6 polyunsaturated fat).
Other: Saturated fatty acids diet
During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0% from carbohydrates; 35.0% from fat: 13.4% from saturated fat; 15.3% from monounsaturated fat; 4.0% from n-6 polyunsaturated fat).

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01934543

Contacts
Contact: Patrick Couture, MD,FRCP,PhD 418-654-2106 patrick.couture@crchul.ulaval.ca
Contact: André Tremblay, PhD 418-656-2131 ext 11417 andre.tremblay@fsaa.ulaval.ca

Locations
Canada
Institute of Nutrition and Functional Foods (INAF) Not yet recruiting
Quebec, Canada, G1V 0A6
Contact: Patrick Couture, MD, FRCP,PhD    418-654-2106    patrick.couture@crchul.ulaval.ca   
Contact: André Tremblay, PhD    418-656-2131 ext 11417    andre.tremblay@fsaa.ulaval.ca   
Principal Investigator: Patrick Couture, MD,FRCP,PhD         
Sub-Investigator: André Tremblay, PhD         
Sub-Investigator: Benoît Lamarche, PhD         
Sponsors and Collaborators
Laval University
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Patrick Couture, MD,FRCP,PhD Laval University
  More Information

No publications provided

Responsible Party: Patrick Couture, MD, FRCP, PhD, Laval University
ClinicalTrials.gov Identifier: NCT01934543     History of Changes
Other Study ID Numbers: INAF-PUFA
Study First Received: August 30, 2013
Last Updated: September 3, 2013
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Metabolic Syndrome X
Glucose Metabolism Disorders
Hyperinsulinism
Insulin Resistance
Metabolic Diseases

ClinicalTrials.gov processed this record on October 23, 2014