Clinical trial NCT06129526: Study of the Efficacy and Safety of EPA in Patients With Type-2 Diabetes
Official title: Study of the Effect of Eicosapentaenoic Acid (EPA) on Markers of Atherothrombosis in Patients With Type-2 Diabetes
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Diabetes Type 2
Hypertriglyceridemia
Diabetes Mellitus
Keywords: Atherothrombosis
Biomarkers
Coronary Artery Disease (CAD)
Corn oil
Eicosapentaenoic acid
Endothelial cells
Inflammation
Omega-3
Platelets
Polyunsaturated Fatty Acids (PUFAs)
Lead sponsor: University of Ioannina
Sponsor class: OTHER
Collaborators: name: LIBYTEC Pharmaceutical S.A.
First posted: 2023-11-13
Enrollment: 450
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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. Exclusion criteria will also include a. HbA1c levels \>10.0%, b. history of acute or chronic pancreatitis, c. known hypersensitivity to fish or shellfish or to the components of the study product or placebo.

Primary outcomes:
measure: The percentage (%) change in plasma levels of triglycerides and markers of inflammation, coagulation, endothelial cell and platelet activation.
timeFrame: 3 months
measure: Number of participants who suffer from bleeding events as defined by the Bleeding Academic Research Consortium (BARC) criteria during the entire follow-up period.
timeFrame: 3 months
Secondary outcomes:
measure: The percentage (%) change in plasma levels of triglycerides.
timeFrame: 3 months
measure: The percentage (%) change in markers of inflammation.
timeFrame: 3 months
measure: The percentage (%) change in markers of coagulation.
timeFrame: 3 months
measure: The percentage (%) change in markers of endothelial cell activation.
timeFrame: 3 months
measure: The percentage (%) change in markers of platelet activation.
timeFrame: 3 months
measure: Number of participants who suffer from the secondary safety end points which are Atrial fibrillation, Palpitations, Arrhythmias, Heart failure, Pneumonia, Peripheral edema, Diarrhea.
timeFrame: 3 months
Other outcomes:
Locations:
city: Ioannina
country: Greece
facility: Atherothrombosis Research Centre / Laboratory of Biochemistry, University of Ioannina
state: Epirus
Study officials:
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