Diabetes Type 2, Hypertriglyceridemia, Diabetes Mellitus
Conditions
Keywords
Atherothrombosis, Biomarkers, Coronary Artery Disease (CAD), Corn oil, Eicosapentaenoic acid, Endothelial cells, Inflammation, Omega-3, Platelets, Polyunsaturated Fatty Acids (PUFAs)
Brief summary
Investigation of the efficacy and safety of an Eicosapentaenoic acid (EPA) supplement versus a placebo supplement on plasma triglyceride levels as well as inflammatory, thrombotic, endothelial and platelet activation markers, in patients with type-2 diabetes mellitus (DM-2).
Detailed description
The conflicting results of previous clinical trials regarding the clinical efficacy of omega-3 fatty acids, such as the STRENGTH and REDUCE-IT studies, as well as the published comments for the placebo used in the REDUCE-IT study (mineral oil), highlight the need for additional studies (pharmacodynamic, clinical, and basic research studies). The SEASIDE (Study of the Effect of Eicosapentaenoic acid, EPA, on Markers of Atherothrombosis in Patients with Type-2 Diabetes) is a phase 4 clinical study, aiming to investigate the efficacy of the dietary supplement EPAVasc, consisted of 1,875mg EPA / 125mg Docosahexaenoic acid (DHA) / 3.75μg Vitamin D / 12mg tocopherol, in reducing the plasma levels of triglycerides, markers of inflammation, coagulation, and platelet as well as endothelial functionality, in high or very high cardiovascular risk DM-2 patients, as compared with the administration of a placebo dietary supplement (Corn Oil). The safety of administering the above EPA supplementation to these patients will be also investigated. This study is expected to significantly advance the existing knowledge regarding the efficacy of EPA in reducing important cardiovascular risk biomarkers in high or very high cardiovascular risk DM-2 patients.
Interventions
DIETARY_SUPPLEMENTEPAVasc
EPAVasc: 1,875mg EPA / 125mg DHA / 3.75μg Vitamin D / 12mg tocopherol
DIETARY_SUPPLEMENTCorn Oil
Corn Oil
Sponsors
LIBYTEC Pharmaceutical S.A.
University of Ioannina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The study will enroll DM-2 patients at high or very high cardiovascular risk, aged ≥ 50 years. Patients should have at least one additional cardiovascular risk factor (such as smoking, hypertension, HDL-cholesterol ≤40 mg/dL for Men, or ≤50mg/dL for Women, high-sensitivity C-reactive protein (hs-CRP)\> 3mg/L, renal dysfunction (CrCl 30-60 mL/min), Ankle-Brachial Index (ABI) \<0.9 (without symptoms of intermittent claudication). In addition, patients enrolled in the study will exhibit triglyceride levels \>135 mg/dL and \<500 mg/dL, despite adherence to the dietary recommendations given for their disease. These recommendations should be followed by all patients during the study. In addition to antidiabetic treatment, patients will receive statin or statin-ezetimibe combination therapy for at least 4 weeks prior to the first visit and should have LDL-cholesterol levels \<100mg/dL. Antidiabetic and hypolipidemic treatment will remain unchanged during the study. All patients will sign a written informed consent prior to their inclusion in the study.
Exclusion criteria
1. Patients with a history (≤ 12 months) of acute coronary syndrome (ACS) or ischemic stroke who are receiving antiplatelet therapy. 2. Patients with peripheral arterial disease or carotid artery disease (\>50% stenosis by DOPPLER ultrasound criteria) receiving antiplatelet therapy. 3. Patients receiving monotherapy with any antiplatelet agent. 4. Patients with atrial fibrillation receiving any anticoagulation, or patients with a history of cardioembolic ischemic stroke or hemorrhagic stroke. 5. Patients with severe heart failure, (NYHA IV). 6. Patients with laboratory or clinically diagnosed severe active liver disease or liver failure (child-Pugh staging, score ≥ 5) or renal failure (eGFR \< 30ml/min). 7. Patients with cancer, receiving any anticancer treatment. 8. Patients who are planned to undergo any surgical procedure. 9.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The percentage (%) change in plasma levels of triglycerides and markers of inflammation, coagulation, endothelial cell and platelet activation. | 3 months | The primary composite efficacy endpoint is the percentage (%) change in each participant in plasma levels of triglycerides and markers of inflammation, coagulation, endothelial cell and platelet activation, comparing the placebo supplement and the investigating supplement. |
| Number of participants who suffer from bleeding events as defined by the Bleeding Academic Research Consortium (BARC) criteria during the entire follow-up period. | 3 months | The Primary safety endpoint is major bleeding according to BARC (Bleeding Academic Research Consortium) criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The percentage (%) change in markers of coagulation. | 3 months | The secondary efficacy endpoint is the (%) change in markers of coagulation specifically Tissue Factor (pg/ml) and Thrombin Time (sec). |
| The percentage (%) change in markers of endothelial cell activation. | 3 months | The secondary efficacy endpoint is the (%) change in markers of endothelial cell activation specifically Monocyte Chemotactic Protein-1 (MCP-1) (pg/ml), Vascular Endothelial Cell Adhesion Molecule-1 (VCAM-1) (ng/mL) and von Willebrand Factor (vWF) (mIU/ml). |
| The percentage (%) change in plasma levels of triglycerides. | 3 months | The secondary efficacy endpoint is the (%) change in triglyceride levels of each participant. |
| Number of participants who suffer from the secondary safety end points which are Atrial fibrillation, Palpitations, Arrhythmias, Heart failure, Pneumonia, Peripheral edema, Diarrhea. | 3 months | Secondary safety endpoints are Atrial fibrillation, Palpitations, Arrhythmias, Heart failure, Pneumonia, Peripheral edema, Diarrhea. |
| The percentage (%) change in markers of platelet activation. | 3 months | The secondary efficacy endpoint is the (%) change in markers of platelet activation specifically soluble P-selectin (sP-selectin) (ng/ml), sCD40L (pg/ml) and Thromboxane A2 (TxA2) (pg/ml). |
| The percentage (%) change in markers of inflammation. | 3 months | The secondary efficacy endpoint is the (%) change in markers of inflammation, specifically Interleukin-1beta (IL-1β) (pg/ml) and Interleukin-6 (IL-6) (pg/ml). |
Countries
Greece
Outcome results
None listed