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
  Purpose

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.


Condition Intervention
Metabolic Syndrome
Insulin Resistance
Drug: omega-3 fatty acid
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Fish Oils on Inflammation and Insulin Resistance

Resource links provided by NLM:


Further study details as provided by University of Kentucky:

Primary Outcome Measures:
  • Treatment of insulin resistant subjects with fish oils will reduce adipose tissue inflammation. [ Time Frame: December 2009 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Fish oils improve peripheral insulin sensitivity through a reduction of intramyocellular lipid. [ Time Frame: December 2009 ] [ Designated as safety issue: No ]

Estimated Enrollment: 135
Study Start Date: January 2007
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
4g Lovaza (omega-3 fatty acid) daily.
Drug: omega-3 fatty acid
4g of omega-3 fatty acid daily by mouth for 12 weeks.
Other Name: Lovaza
Placebo Comparator: 2
placebo (4 non-active capsules daily)
Drug: placebo
4 inert capsules daily by mouth for 12 weeks.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   35 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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)
  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: NCT00579436

Contacts
Contact: Philip Kern, MD 859-323-4933 pake222@email.uky.edu
Contact: Laura L Ashe, CCRC 859-323-2782 laura.ashe@uky.edu

Locations
United States, Kentucky
University of Kentucky Medical Cener Recruiting
Lexington, Kentucky, United States, 40475
Contact: Philip Kern, MD    859-323-4933    pake222@email.uky.edu   
Principal Investigator: Philip A Kern, M.D.         
Sponsors and Collaborators
Philip Kern
GlaxoSmithKline
Investigators
Principal Investigator: Philip A. Kern, M.D. University of Kentucky
  More Information

Publications:
Responsible Party: Philip Kern, Professor of Medicine, University of Kentucky
ClinicalTrials.gov Identifier: NCT00579436     History of Changes
Other Study ID Numbers: 74457
Study First Received: December 20, 2007
Last Updated: July 23, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of Kentucky:
inflammation
obesity
diabetes

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

ClinicalTrials.gov processed this record on October 16, 2014