Omega-3 PUFA Suppress Adipochemokines
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Change in Plasma Fractalkine Levels
研究概览
简要总结
This study is a clinical trial designed to assess whether fish oil treatments are effective in the prevention of obesity-related fat tissue (adipose) inflammation. Specifically it addresses the hypothesis that fish oils treatments will reduce signaling by chemokine pathways (fractalkine and MCP-1) important in adipose tissue for the recruitment and activation of certain white blood cells (macrophages). The study is a double-blind placebo-controlled trial of the fish oil Lovaza from GlaxoSmithKline (omega-3-acid ethyl esters; a combination of ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) in obese non-diabetic adults, to determine if Lovaza decreases markers of inflammation and macrophage activation in adipose and blood and understand the mechanism by which fish oils affect inflammation.
详细描述
We propose to conduct a parallel arm, double blind, placebo-controlled trial to understand the anti-inflammatory and metabolic effects of marine derived omega-3 fatty acids (EPA + DHA) on obesity-related inflammation and chemokine signaling in humans. Obese (BMI>30 kg/m2) but non-diabetic young males and females (n~44; 25 to 50 years of age) taking no omega-3 fatty acid (EPA + DHA) supplements and consuming a low fish diet (defined as usual intake of high omega-3 fish (tuna and other non-fried fish) < 3 to 4 servings per month) will be included. A low habitual fish intake is important to control EPA + DHA intake during the supplement period (see exclusion criteria below). Subjects also will be required to maintain their current fish intake throughout the treatment period.
There will be two treatment groups; (1) placebo and (2) omega-3 fatty acids 4 grams/day. The trial will be randomized, double blind, placebo-controlled, with parallel treatment groups; treatment with omega-3 fatty acids 8 weeks. We will enroll participants until at least 22 subjects per study-arm complete all study visits (i.e., at least 44 participants).
Prescription Lovaza (omega-3-acid ethyl esters) from GlaxoSmithKline at 4 grams day (2 1-gram capsules twice daily, with food) will be used. We expect this dose to be safe because it is a dose that is recommended, and routinely used, for management of moderate or worse hypertriglyceridemia (levels > 400 mg/dL). We will use matching placebo capsules so that all participants are taking 2 capsules twice daily - with food as recommended in clinical practice.
The study duration was chosen in order to provide adequate time for potential anti-inflammatory effects of treatments without requiring maximum lipid modifying effects while also reducing the potential for drop-out and loss to follow up that is associated with longer study durations.
Participants will be recruited from the Preventive Cardiology Research databases, comprised of healthy subjects who have participated in previous research studies and who have asked to be contacted for future studies. Potential participants will also be recruited via local IRB-approved flyers, internet, and newspaper advertisements (see flyer and advertisement attached) targeting the Delaware Valley region.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 25 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and non-pregnant/lactating women between the ages of 25 and
- •Body Mass Index (BMI) ≥30 kg/m2
- •Participants who are able to give written informed consent and willing to comply with all study-related procedures.
排除标准
- •Diabetes Mellitus (glucose fasting >126, or random >200, Hemoglobin A1C>6.5 %, or use of any anti-diabetic agent)
- •Self-reported fish or shellfish allergy
- •Planned usage of any prescription or non-prescription medication (other than contraceptive pills or devices) during the study period.
- •Recent (within 6 months) use of fish oil supplements or self- reported dietary intake of >3 servings of fish/month
- •Blood pressure >140/90
- •Recent (within 6 months) use of statins, niacin, or fenofibrates
- •Current or planned pregnancy/lactation. Pre-menopausal women unwilling to prevent pregnancy by use of the following approved contraceptive strategies: diaphragm, cervical cap, condom with spermicide, surgical sterility, birth control pills, Depo-Provera injection, Intra-uterine device, progestin implant, or abstinence.
- •History of liver disease or abnormal liver function tests (aspartate aminotransferase, Alanine transaminase, Alkaline Phosphatase, gamma-glutamyl transpeptidase > 1.5x Upper Limit normal; bilirubin > 2x upper limit normal) at Screening Visit
- •Men who are unwilling to limit alcohol consumption to < 14 alcoholic drinks per week or < 4 alcoholic drinks per occasion while participating in the study
- •Women who are unwilling to limit alcohol consumption to < 7 alcoholic drinks per week or < 3 alcoholic drinks per occasion while participating in the study.
- •Hemoglobin less than 11.0 g/dL
- •Any reported arrhythmia, usage of anti-arrhythmic therapy, or abnormal screening electrocardiogram
- •Known bleeding disorder or coagulopathy
- •Any major active rheumatologic, pulmonary, hematologic or dermatologic disease or inflammatory condition or minor active infection
- •Self-reported history of HIV positive
- •Patients who have undergone any organ transplant
- •Individuals who currently use tobacco products or have done so in the previous 30 days
- •Treatment with aspirin, non steroidal anti-inflammatories, COX-2 inhibitors, steroids or any immunomodulatory therapy 2 weeks prior to the Screening Visit
- •Participants who are unwilling to eliminate omega-3 fatty acid (EPA + DHA) supplements and/or fortified food, or have their usual intake of high omega-3 fish (tuna and other non-fried fish) be > 3 to 4 servings per month as assessed by a simple screening questionnaire
- •Recent (within 6 months) treatment with coumarin-type anticoagulants
- •Positive urine pregnancy test result.
- •Self-reported history of injected recreational drug use.
- •Any medical condition or abnormal laboratory value that is judged clinically significant by an investigator
研究组 & 干预措施
Lovaza
Lovaza 4 grams daily (2 1-gram capsules twice daily) will be given for 8 weeks
干预措施: Lovaza (Drug)
Placebo
An inactive Placebo (2 pills twice daily) will be given for 8 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Plasma Fractalkine Levels
时间窗: Baseline and 8 weeks
Quantification of fractalkine levels in plasma at baseline and after 8 weeks of Lovaza or placebo will be compared.
次要结局
- Change in mRNA Levels of MCP-1 in Adipose(Baseline and 8 weeks)
- Change in Plasma Monocyte Chemotactic Protein-1 (MCP-1)(Baseline and 8 weeks)
- Change in the Ratio of Circulating Monocyte Subpopulations(baseline and 8 weeks)
- Change in mRNA Expression of Fractalkine in Adipose(Baseline and 8 weeks)
- Change in mRNA Levels of IL6 in Adipose(Baseline and 8 weeks)
- Change in mRNA Levels of TNFalpha in Adipose(Baseline and 8 weeks)
- Change in Ratio of Adipose Tissue Macrophage Subpopulation(Baseline and 8 weeks)
- Change in Plasma Tumor Necrosis Factor Alpha (TNFalpha)(Baseline and 8 weeks)
- Change in Plasma Interleukin 6 (IL-6)(Baseline and 8 weeks)