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Effects of N-3 Polyunsaturated Fatty Acids On Chylomicron Secretion And Expression Of Genes That Regulate Intestinal Lipid Metabolism In Men With Type 2 Diabetes (DBB48)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Patrick Couture, Laval University
ClinicalTrials.gov Identifier:
NCT01449773
First received: October 6, 2011
Last updated: February 28, 2013
Last verified: February 2013
History of Changes
  Purpose

The overaccumulation of apoB-48-containing lipoproteins of intestinal origin seen in patients with type 2 diabetes are now thought to be attributable to elevated intestinal production and reduced clearance. Substantial evidence exists indicating that elevated plasma levels of these lipoproteins are associated with increased cardiovascular disease risk. Therefore, reduction of atherogenic plasma triglyceride-rich lipoproteins (TRL) levels of intestinal origin appears to be crucial to improve CVD risk associated with type 2 diabetes. In this regard, n-3 PUFAs have been shown to exert beneficial effects on diabetic dyslipidemia. However, the investigators understanding of the physiological changes that occur with n-3 PUFA supplementation is suboptimal, thereby limiting the investigators appreciation of its impact on CVD risk associated with type 2 diabetes. The effects of n-3 PUFAs on the intestinal production of TRLs and the expression of genes regulating intestinal lipid absorption and chylomicron synthesis have not yet been examined in humans. The general objective of the proposed research is to investigate the mechanisms by which n-3 PUFAs beneficially modify intestinal lipoprotein metabolism in patients with type 2 diabetes. The investigators hypothesize that n-3 PUFA supplementation in men with type 2 diabetes will:

  • reduce TRL apoB-48 production rate and increase fractional catabolic rate of these lipoproteins,
  • decrease the expression of genes that regulate intestinal lipid absorption and synthesis as well as synthesis of apoB-48-containing lipoproteins,
  • decrease both plasma surrogates of cholesterol absorption and cholesterol synthesis.

Condition Intervention
Type 2 Diabetes
 Dietary Supplement: n-3 PUFAs
Dietary Supplement: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Effects of N-3 Polyunsaturated Fatty Acids On Chylomicron Secretion And Expression Of Genes That Regulate Intestinal Lipid Metabolism In Men With Type 2 Diabetes

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Laval University:

Primary Outcome Measures:
  • Change in the in vivo kinetics of intestinally derived apoB-48-containing lipoproteins between the two 8-week interventions [ Time Frame: At the end of the two 8-week interventions ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in the expression of genes that regulate intestinal lipid absorption (NPC1L1, ABCG5/8, FABP, SREBP-1c) and synthesis (DGAT, ACAT2, HMG CoA reductase) as well as synthesis of apoB-48-containing lipoproteins (MTP)between the two 8-week interventions [ Time Frame: At the end of the two 8-week interventions ] [ Designated as safety issue: No ]
  • Change in the plasma surrogates of cholesterol absorption (campesterol, beta-sitosterol) and synthesis (lathosterol) between the two 8-week interventions [ Time Frame: At the end of the two 8-week interventions ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: April 2008
Study Completion Date: January 2013
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: n-3 PUFAs Dietary Supplement: n-3 PUFAs
5 capsules/day in order to provide 3 g/day of n-3 PUFAs.
Placebo Comparator: Corn and soybean oil pill Dietary Supplement: Placebo
5 capsules/day containing corn and soybean oil

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age between 18 and 55 years,
  • plasma TG levels above the 50th percentile for age,
  • non-smoker,
  • BMI between 25.0 and 40.0 kg/m2,
  • stable body weight for at least 6 months prior to the study baseline,
  • HbA1c between 6.5 and 8.5%,
  • baseline fasting plasma glucose < 15.0 mmol/L
  • patients with de novo type 2 diabetes not taking oral hypoglycemic agents -- - or patients having received stable doses of metformin for at least 3 months before randomization.

Exclusion Criteria:

  • extreme dyslipidemias such as familial hypercholesterolemia,
  • patients with secondary form of diabetes or acute metabolic diabetic complications,
  • patients having received or being treated with insulin or a thiazolidinedione within the past 6 months,
  • subjects having CVD (CHD, cerebrovascular disease or peripheral arterial disease)
  • subjects taking medications known to affect lipoprotein metabolism (e.g. steroids, beta blockers, thiazide diuretics, lipid lowering agents,
  • significant alcohol intake
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01449773

Locations
Canada
Laval University
Quebec, Canada, G1V 0A6
Sponsors and Collaborators
Laval University
Investigators
Principal Investigator: Patrick Couture, MD, PhD, FRCP Laval University
  More Information

No publications provided

Responsible Party: Patrick Couture, Professor, Laval University
ClinicalTrials.gov Identifier: NCT01449773     History of Changes
Other Study ID Numbers: INAF-117.05.01
Study First Received: October 6, 2011
Last Updated: February 28, 2013
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on May 16, 2013