Lipid Metabolism Disorders, Hypertriglyceridemia
Conditions
Keywords
Fish oil, Atherogenic lipidemia, Lipoproteins
Brief summary
The goal of this study is to learn more about omega-3 polyunsaturated fatty acids supplementation on blood lipid profile and platelets in patients with high cholesterol levels. The purpose of this research is to gather information on the safety and effect of two different fish oils, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Participants will: Visit the clinic 3 times during study checkups, tests and blood collection. Randomized to either the EPA or the DHA supplementation group. Be given a 28-day food and activity log.
Detailed description
Epidemiological studies suggest that consumption of omega-3 polyunsaturated fatty acids (n-3 PUFAs) derived from fish oil, mainly consisting of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is associated with lower cardiovascular risk. However, interventional clinical trials aimed at reducing cardiovascular incidents by n-3 PUFAs supplementations have yielded inconsistent results. An intriguing fact is that only the outcome trials using EPA, but not those testing EPA/DHA mixed regimens, showed beneficial results. This discrepancy begs the question of whether EPA and DHA have differential effects and whether DHA blunts the cardiovascular benefits of EPA. However, no head-to-head clinical trial comparison of the biological effects of EPA and DHA in the hyperlipidemia patients has been reported. Hence, a well-designed, controlled, proof-of-concept clinical study testing EPA versus DHA in a relevant population is urgently required. In this study, the human subjects with atherogenic dyslipidemia will be randomized to dietary supplementation with four grams of either EPA or DHA n-3 PUFAs for eight weeks. At baseline and after the supplementation, various markers of thrombogenesis will be assessed, including biomarkers of the clotting cascade, thromboelastography, urinary thromboxane metabolites, whole blood aggregation, platelet aggregation, and flow cytometry analysis of platelets and platelet-leukocyte aggregates will also be performed.
Interventions
DRUGEPA
Fish oil
DRUGDHA
Fish oil
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
The Miriam Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
* Fasting TG levels ≥ 150 mg/dL and \< 500 mg/dL and HDL-C ≤ 40 (men) or ≤ 50 (women) * LDL-C \> 40 mg/dL and ≤ 130 mg/dL * Able to provide informed consent and adhere to study schedules * Agree to follow and maintain a relatively stable and low fatty fish intake diet (\<3 servings per week)
Exclusion criteria
* Female with pregnancy, planned pregnancy (within the study period), or currently breastfeeding. * Subjects with weight changes greater than 20% over the past 3 months * Subjects planning a significant change in diet or exercise levels * Malabsorption syndrome and/or chronic diarrhea * Use of dietary supplements containing n-3 PUFA fatty acids * Frequent consumption of n-3 PUFA-enriched fish (\>3 times a week) * Abnormal liver, kidney, or thyroid functions * Drug or alcohol abuse within 6 months or significant mental/psychological impairment * Current smokers * Subjects taking daily aspirin, NSAIDs, anticoagulant, or corticosteroids * Subjects with known bleeding disorders (for example, hemophilia) * Known sensitivity or allergy to fish, shellfish, or omega-3 fatty acid supplements * Subjects requiring regular transfusions for any reason * No ethnic/racial groups will be excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Platelet Aggregation Area Under the Curve (AUC) Over Time | 8 weeks | Platelet aggregation will be assessed as the primary endpoint. The percentage of platelet aggregation will be measured at multiple time points, and the area under the curve (AUC) will be calculated to serve as a comprehensive marker of platelet aggregation response. Data will be presented as mean ± standard deviation or other appropriate statistical summaries. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Thromboxane Metabolite Levels normalized to urinary creatinine levels in ng/mmol | 8 weeks | Urinary thromboxane metabolite levels will be measured as a secondary endpoint to evaluate thromboxane production. Quantification will be conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results will be normalized to urinary creatinine levels (nanograms per millimole of creatinine) to account for variations in urine concentration. Data will be summarized using statistical measures such as mean ± standard deviation or other appropriate metrics. |
| Plasma levels of CRP in mg/L | 8 weeks | Inflammatory markers will be measured as secondary endpoints to evaluate systemic inflammation. Plasma levels of C-reactive protein (CRP) will be reported in milligrams per liter (mg/L) using enzyme-linked immunosorbent assay (ELISA) or similar validated methods. Data will be summarized using statistical measures such as mean ± standard deviation, and comparisons will be made across study groups and time points. |
| Plasma levels of resolvins in pg/mL | 8 weeks | Specialized pro-resolving mediators (SPMs) will be measured as secondary endpoints to assess their role in inflammation resolution. Plasma levels of resolvins will be quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and reported in picograms per milliliter (pg/mL). Data will be summarized using statistical measures such as mean ± standard deviation, and comparisons will be made across study groups and time points. |
| Percentage of Activated Platelets as Assessed by Flow Cytometry | 8 weeks | Platelet activation will be assessed as a secondary endpoint. The percentage of activated platelets will be measured using flow cytometry, focusing on markers such as P-selectin expression and fibrinogen binding to the GPIIb/IIIa receptor. Measurements will be taken at multiple time points, and data will be summarized using statistical measures such as mean ± standard deviation. |
| Plasma Levels of TNF-α in pg/mL | 8 weeks | Inflammatory markers will be measured as secondary endpoints to evaluate systemic inflammation. Plasma levels of tumor necrosis factor-alpha (TNF-α) will be quantified in picograms per milliliter (pg/mL) using enzyme-linked immunosorbent assay (ELISA) or similar validated methods. Data will be summarized using statistical measures such as mean ± standard deviation, and comparisons will be made across study groups and time points. |
| Plasma levels of protectins in pg/mL | 8 weeks | Specialized pro-resolving mediators (SPMs) will be measured as secondary endpoints to assess their role in inflammation resolution. Plasma levels of protectins will be quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and reported in picograms per milliliter (pg/mL). Data will be summarized using statistical measures such as mean ± standard deviation, and comparisons will be made across study groups and time points. |
| Plasma levels of maresins in pg/mL | 8 weeks | Specialized pro-resolving mediators (SPMs) will be measured as secondary endpoints to assess their role in inflammation resolution. Plasma levels of maresins, will be quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and reported in picograms per milliliter (pg/mL). Data will be summarized using statistical measures such as mean ± standard deviation, and comparisons will be made across study groups and time points. |
| Plasma Levels of IL-6 in pg/mL | 8 weeks | Inflammatory markers will be measured as secondary endpoints to evaluate systemic inflammation. Plasma levels of interleukin-6 (IL-6) will be quantified in picograms per milliliter (pg/mL) using enzyme-linked immunosorbent assay (ELISA) or similar validated methods. Data will be summarized using statistical measures such as mean ± standard deviation, and comparisons will be made across study groups and time points. |
Countries
United States
Contacts
Primary ContactWenliang Song, MD
Backup ContactDaria Salamevich
Outcome results
None listed