Metabolic Actions of Omega-3 Fatty Acids

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Maryland
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Michael Miller, University of Maryland
ClinicalTrials.gov Identifier:
NCT01896414
First received: June 18, 2013
Last updated: July 2, 2014
Last verified: July 2014
  Purpose

The metabolic syndrome raises the risk of heart disease and is currently at epidemic proportions in the U.S. It consists of 3 of the following components: central obesity, high triglycerides, low HDL, abnormal blood pressure and impaired fasting glucose levels. Previous studies have suggested that omega-3 fish oil may influence some of these components but the mechanisms involved are not well understood. Therefore, this proposal will investigate how omega-3 fish oils affect inflammation, lipids and fat breakdown by comparing it to placebo. Favorable outcomes from this study could translate into a new approach to improve heart disease risk in men and women with the metabolic syndrome.


Condition Intervention
Metabolic Syndrome
Dietary Supplement: EPA (marine fatty acids)
Dietary Supplement: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Metabolic Actions of Omega-3 Fatty Acids on Inflammation and Adipocyte Lipolysis in the Metabolic Syndrome

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Biochemical measurements of lipids, glucose homeostasis, inflammatory markers, and adipocyte responses to mediators of lipolysis [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Metabolic (e.g., lipoproteins, inflammatory cytokines, acute phase reactants, glucose tolerance/insulin resistance) and adipose tissue responses (basal and insulin suppression of lipolysis (ED50), LPL activity, cytokine release and lipogenesis).


Secondary Outcome Measures:
  • Determination of regional fat distribution, visceral and subcutaneous adipose volume and body composition [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Regional fat distribution quantified anthropometrically as waist and hip circumference, visceral and subcutaneous adipose volumes and muscle lipid accumulation by CT-scan and body composition (total and regional fat mass) by dual energy absorptiometry (DXA).


Estimated Enrollment: 30
Study Start Date: July 2014
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EPA (marine fatty acids)
Subjects will receive EPA , four 1 gram capsules daily.
Dietary Supplement: EPA (marine fatty acids)
Subjects will be randomized to receive either EPA or placebo, four 1 gram capsules daily.
Placebo Comparator: Placebo
Subjects will be randomized to receive placebo, four 1 gram capsules daily.
Dietary Supplement: Placebo
Subjects will be randomized to receive either EPA/ or placebo, four 1 gram capsules daily.

Detailed Description:

Metabolic Actions of Omega-3 Fatty Acids on Inflammation and Adipocyte Lipolysis in the Metabolic Syndrome

Epidemiological studies identify metabolic syndrome (MetS) as a biomarker of cardiovascular disease (CVD) risk, and recent AHA scientific statements recommend intensive lifestyle diet and exercise measures to reduce risk. Marine-derived omega-3 polyunsaturated fatty acids such as, eicosapentanoic acid (EPA) improve many constituents of the metabolic syndrome such as lowering fasting TG and glucose levels, inflammation, insulin resistance and blood pressure. These improvements may be mediated by increased fat cell storage and metabolism and lipids, reducing inflammation and ectopic fat deposition in visceral abdominal tissue, muscle and liver that results in excessive pro-inflammatory intra-abdominal fat (IAF), insulin resistance and reduced levels of HDL cholesterol, hallmark characteristics of the MetS. The anti-inflammatory actions of EPA lower acute phase reactants (APRs) and proinflammatory mediators are mechanisms for their lipid lowering and insulin sensitizing effects to reduce CVD risk. The systematic investigation of marine-derived omega-3 PUFAs on these inflammatory, metabolic and physiological parameters will provide new mechanistic insights for the therapeutic use of a potentially beneficial, safe nutraceutical, EPA in patients with MetS. Thus, it is our hypothesis that supplementation of marine-derived omega-3 PUFAs, will reduce constituents of MetS as well as systemic and tissue inflammation, insulin resistance (HOMA-IR), adipocyte lipolysis and cytokine release from AT to enhance TG storage capacity of subcutaneous AT. The reduction in inflammation and increase in insulin sensitivity will remodel adipose tissue to function more efficiently in TG uptake and storage; thus, reducing circulating FFAs and cytokines. We postulate that these metabolic effects may decrease ectopic fat deposition in viscera (IAF and muscle), an intriguing, novel outcome that provides rationale for the 9 month treatment.

The Specific Aims are to conduct a pilot 9 month randomized trial in adults with high Tg and at least one other component of the MetS to compare the effects of EPA vs. placebo on:

Aim 1: Metabolic (e.g., lipoproteins, inflammatory cytokines, acute phase reactants, glucose tolerance/insulin resistance) and adipose tissue responses (basal and insulin suppression of lipolysis (ED50), LPL activity, cytokine release and lipogenesis).

Aim 2: Regional fat distribution quantified anthropometrically as waist and hip circumference, visceral and subcutaneous adipose volumes and muscle lipid accumulation by CT-scan and body composition (total and regional fat mass) by dual energy absorptiometry (DXA).

These outcomes have potentially intriguing therapeutic implications for marine derived omega-3 PUFA supplementation as part of a lifestyle program for patients at increased cardiometabolic risk.

  Eligibility

Ages Eligible for Study:   25 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Metabolic Syndrome, including 2 of the following:

    1. Treated Hyperlipidemia or Untreated Triglycerides > 150 mg/dL
    2. Waist circumference (inches) > 35 (women) or >40 (men)
  • And at least 1 additional factor:
  • Treated Hypertension or Untreated Blood pressure >130/85 and < 160/100 mm Hg
  • HDL-C < 40 mg/dL men < 50 mg/dL women
  • Glucose > 100mg/dL and HbA1c < 6.1%

Exclusion Criteria:

  • Fasting TG > 500 mg/dL or LDL > 180 mg/dL
  • Fasting glucose> 125 mg/dL or history of diabetes mellitus
  • Hematologic or malignant disorders
  • Morbid Obesity (BMI > 50 kg/m2)
  • Endocrine (thyroid) or metabolic disorders (unless treated and under control)
  • Alcohol consumption greater than (2) 4-ounce glasses of table wine, (2) 12-oz bottles of beer or 2 shots of spirits in men or women
  • Active IV drug abuse within the past 6 months
  • Clinical depression (per PI evaluation)
  • Immunosuppressive or other therapy that would interfere with research testing
  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: NCT01896414

Contacts
Contact: Faith Pa'ahana-Brown, RN 410 328-4433 fpaahana@medicine.umaryland.edu

Locations
United States, Maryland
University of Maryland Medical Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Faith Pa'ahana-Brown, RN    410-328-4433    fpaahana@medicine.umaryland.edu   
Principal Investigator: Michael Miller, MD         
Sub-Investigator: Andrew P Goldberg, MD         
United States, Pennsylvania
Amish Research Center Recruiting
Lancaster, Pennsylvania, United States, 17601
Contact: Mary Morrissey, RN, BSN    717-392-4948    mmorrissey@medicine.umaryland.edu   
Contact: Sylvia Newcomer, MT    717-392-4948    snewcom@medicine.umaryland.edu   
Sub-Investigator: Robert Reed, MD         
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Michael Miller, M.D. University of Maryland
  More Information

Additional Information:
No publications provided

Responsible Party: Michael Miller, Cardiologist, University of Maryland
ClinicalTrials.gov Identifier: NCT01896414     History of Changes
Other Study ID Numbers: 00052080, R21HL113576-01
Study First Received: June 18, 2013
Last Updated: July 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Maryland:
Metabolic Syndrome
Omega 3 Fish Oil

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

ClinicalTrials.gov processed this record on July 24, 2014