Effects of Fish Oils on Inflammation and Insulin Resistance

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by University of Kentucky
Sponsor:
Collaborators:
GlaxoSmithKline
Information provided by (Responsible Party):
Philip Kern, University of Kentucky
ClinicalTrials.gov Identifier:
NCT00579436
First received: December 20, 2007
Last updated: July 23, 2013
Last verified: July 2013

December 20, 2007
July 23, 2013
January 2007
December 2013   (final data collection date for primary outcome measure)
Treatment of insulin resistant subjects with fish oils will reduce adipose tissue inflammation. [ Time Frame: December 2009 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00579436 on ClinicalTrials.gov Archive Site
Fish oils improve peripheral insulin sensitivity through a reduction of intramyocellular lipid. [ Time Frame: December 2009 ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Effects of Fish Oils on Inflammation and Insulin Resistance
Effects of Fish Oils on Inflammation and Insulin Resistance

The purpose of this study is to determine whether improvement in fat and muscle metabolism after the treatment with Omacor (fish oils) provides insight into the link between obesity, fat and muscle function leading to metabolic syndrome, which is a risk factor for heart disease and diabetes.

The development of type 2 diabetes (T2DM) represents a complex series of events, involving abnormalities in adipose tissue lipid distribution and insulin action. Along with an increase in adipose tissue mass is an increase in inflammation brought about by macrophages that infiltrate adipose tissue. These macrophages express inflammatory cytokines such as TNF- and IL-6, which are correlated with insulin resistance and metabolic syndrome, and suggest that metabolic syndrome and diabetes are conditions characterized by a state of chronic, low-grade inflammation. Thiazolidinediones (TZDs) improve insulin sensitivity via activation of PPAR- , and there is much evidence that PPAR agonists also have anti-inflammatory properties.

Fish oils are rich sources of Omega-3 fatty acids and there is a large literature on the potential benefits of fish oils on lowering serum triglycerides, cardiovascular protection, and immune modulation, and there is evidence that fish oils also activate PPAR . Hence, the focus of this study will be on subjects with insulin resistance and metabolic syndrome, but who do not yet have diabetes. We plan to treat insulin resistant subjects with fish oils and ask the following questions.

Hypothesis 1. The treatment of insulin resistant subjects with fish oils will reduce adipose tissue inflammation.

Aim 1. From blood samples drawn before and after treatment, we will measure levels of circulating inflammatory cytokines.

Aim 2. Adipose tissue biopsies will be performed before and after fish oil treatment. From the adipose biopsies, we will quantitate cytokine expression, macrophage number, and we will look for evidence of macrophage apoptosis.

Aim 3. We will determine whether fish oil treatment increases the adipose tissue secretion and serum level of the high molecular weight form of adiponectin.

Hypothesis 2. The reduction in inflammatory markers occurs through an activation of PPAR by the fish oils.

Aim 4. Adipose tissue and macrophages will be treated in vitro with fish oils in the presence and absence of a PPAR inhibitor. We will determine whether fish oils stimulate the secretion of the high molecular weight adiponectin isoform from adipose tissue and whether they induce apoptosis from macrophages, and whether this process is inhibited by the PPAR inhibitor.

Hypothesis 3. Fish oils improve peripheral insulin sensitivity through a reduction in intramyocellular lipid, and an improvement in muscle insulin signal transduction.

Aim 5. Before and after treatment with fish oils, insulin sensitivity will be measured, along with intramyocellular lipid and genes involved in insulin action and muscle lipid oxidation.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
  • Metabolic Syndrome
  • Insulin Resistance
  • Drug: omega-3 fatty acid
    4g of omega-3 fatty acid daily by mouth for 12 weeks.
    Other Name: Lovaza
  • Drug: placebo
    4 inert capsules daily by mouth for 12 weeks.
  • Active Comparator: 1
    4g Lovaza (omega-3 fatty acid) daily.
    Intervention: Drug: omega-3 fatty acid
  • Placebo Comparator: 2
    placebo (4 non-active capsules daily)
    Intervention: Drug: placebo
Spencer M, Finlin BS, Unal R, Zhu B, Morris AJ, Shipp LR, Lee J, Walton RG, Adu A, Erfani R, Campbell M, McGehee RE Jr, Peterson CA, Kern PA. Omega-3 fatty acids reduce adipose tissue macrophages in human subjects with insulin resistance. Diabetes. 2013 May;62(5):1709-17. doi: 10.2337/db12-1042. Epub 2013 Jan 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
135
December 2013
December 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • BMI 27-45 kg/m2
  • age 35-65 years
  • abnormal carbohydrate metabolism

Exclusion Criteria:

  • triglycerides over 700 mg/dl
  • renal disease
  • liver disease
  • congestive heart failure
  • history of heart disease or stroke
  • chronic aspirin or NSAID use (anti-coagulant)
  • history of a bleeding disorder
  • use of statins, fibrates, ACE inhibitors, angiotensin II receptor blockers and glucocorticoids
  • diet heavy in omega-3 fatty acids (salmon, sardines, flaxseeds)
Both
35 Years to 65 Years
Yes
Contact: Philip Kern, MD 859-323-4933 pake222@email.uky.edu
Contact: Laura L Ashe, CCRC 859-323-2782 laura.ashe@uky.edu
United States
 
NCT00579436
74457
Yes
Philip Kern, University of Kentucky
Philip Kern
  • GlaxoSmithKline
  • National Institutes of Health (NIH)
Principal Investigator: Philip A. Kern, M.D. University of Kentucky
University of Kentucky
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP