Omega-3 Fatty Acids Supplementation and Atherothrombotic Biomarkers in Type 2 Diabetes and Cardiovascular Disease.

NCT02178501 | Completed

• 1 other identifier: 2011/03/B/NZ5/05767
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 2

Brief Summary

The major source of mortality and morbidity of diabetic patients is cardiovascular disease (CVD). Moreover, in CVD patients the presence of diabetes is associated with the increased risk of major adverse cardiac events as compared to patients without diabetes. The pathophysiology of macrovascular complications in T2D is not fully understood and involves: 1/ induction of oxidative stress, 2/ the formation of advanced glycation end products, 3/ activation of blood coagulation and platelet aggregation, 4/ increased inflammation, 5/ altered secretion of adipokines in obese subjects and 6/ endothelial dysfunction. All those mechanisms in T2D patients could potentially be a subject of new therapeutic interventions. A therapy that continues to show promise in T2D patients with CVD is supplementation with omega-3 polyunsaturated fatty acids (PUFA). Clinical studies have indicated that omega-3 PUFA decrease the risk of major cardiovascular events, although the mechanism of action is not completely understood. Moreover, there were no trials exploring the mechanisms and outcomes of omega-3 treatment in T2D patients with CVD. Despite that fact, Polish Diabetes Association guidelines recommend the use of omega-3 PUFA in patients with diabetes in the prevention of macrovascular complications. Moreover, it is unclear whether the benefits of modifying the pathophysiological processes during supplementation with omega-3 PUFA occur only in patients with their deficiency or in all patients with type 2 diabetes. Potential benefits of omega-3 PUFA in such patients are: 1/ decreased oxidative stress, 2/ decreased platelet aggregation and reduction of hypercoagulable state, 3/ anti-inflammatory effects, 4/ improvement in endothelial function. All those effects were explored previously with inconsistent findings. There is very limited information from clinical studies on the mechanisms and benefits of omega-3 PUFA in T2D patients with CVD. The objective of the current study is to evaluate the effects of omega-3 PUFA administered on top of optimal therapy of atherosclerotic vascular disease and T2D on endothelial function, platelet aggregation and thrombotic, inflammatory and oxidative stress biomarkers.

Conditions

Type 2 Diabetes; Cardiovascular Diseases

Keywords

OMEGA-3 PUFA; type 2 diabetes; cardiovascular diseases

Outcome Measures

Primary Outcomes (3)

• Change from Baseline in biomarkers of oxidative stress at 3 months

  8-iso-prostaglandin F2α, oxidized LDL;

  From baseline to 3 months

• Change from Baseline in coagulation status at 3 months

  1. Platelet aggregation (induced by 5 and 20 μmol/L of adenosine diphosphate (ADP) and by 0.5 mmol/L of arachidonic acid; light transmittance aggregometry) 2. Thrombin generation (prothrombin 1.2 fragments, endogenous thrombin potential) 3. Platelet-fibrin clot strength measurements (thromboelastography) 4. Fibrin clot properties (permeability and lysis)

  From baseline to 3 months

• Change from Baseline in endothelial function status 3 months

  1. Flow mediated vasodilation in brachial artery (FMD) 2. Asymmetric Dimethylarginine (ADMA), ICAM-1, VCAM-1, von Willebrand factor

  From baseline to 3 months

Secondary Outcomes (2)

• Change from Baseline in fatty acids metabolism at 3 months

  From baseline to 3 months

• Change from Baseline in glycometabolic control at 3 months

  From baseline to 3 months

Other Outcomes (1)

• Safety Measures

  at 3 months

Study Arms (2)

Omega-3 PUFA

EXPERIMENTAL

OMEGA-3 PUFA 2000 mg once daily (1000 mg EPA and 1000 mg DHA)

Dietary Supplement: Omega-3 PUFA

Placebo

PLACEBO COMPARATOR

Placebo once daily

Dietary Supplement: Omega-3 PUFA

Interventions

Omega-3 PUFA DIETARY_SUPPLEMENT

comparison of omega-3 PUFA supplementation 2000 mg once daily (1000 mg EPA and 1000 mg DHA) versus placebo

Omega-3 PUFA; Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• min. 50 years old at screening
• type 2 of diabetes diagnosed for at least 6 months (regardless of the mode of hypoglycemic therapy)
• HbA1c ≥ 6,5%
• concomitant coronary artery disease (with significant, reversible or irreversible myocardial perfusion defect, providing existing ischemia or history of myocardial infarction) or cerebrovascular or peripheral vascular disease (documented with angiography)

You may not qualify if:

• pregnancy
• type 1 diabetes or poorly controlled T2D (HbA1c \> 9.0%)
• acute myocardial infarction within less than 3 months
• percutaneous coronary intervention, coronary artery bypass grafting, percutaneous transluminal angioplasty or vascular surgery within less than 1 month
• acute infection
• hypertriglyceridemia requiring treatment with omega-3 PUFA
• active bleeding or any known coagulation or bleeding disorders
• concomitant chronic anticoagulant therapy
• platelet count \< 100x109/L
• serum creatinine \> 177 μmol/L (2 mg/dL)
• liver injury (alanine transaminase level \> 1.5 times above the upper limit of the reference range)
• chronic use of nonsteroidal anti-inflammatory drugs other than aspirin
• daily intake of dietary supplements containing omega-3 PUFA within the past month
• known sensitivity or allergy to fish or omega-3 fatty acid supplements
• history of inflammatory disease or vasculitis or corticosteroid therapy

Sponsors & Collaborators

• Jagiellonian University: lead
• National Science Centre, Poland: collaborator

Study Sites (2)

Samodzielny Publiczny Szpital Kliniczny nr 7 Śląskiego Uniwersytetu Medycznego w Katowicach Górnośląskie Centrum Medyczne im. prof. Leszka Gieca

Katowice, 40-635, Poland

Location

Krakowski Szpital Specjalistyczny im. Jana Pawła II

Krakow, 31-202, Poland

Location

Related Publications (1)

• Poreba M, Mostowik M, Siniarski A, Golebiowska-Wiatrak R, Malinowski KP, Haberka M, Konduracka E, Nessler J, Undas A, Gajos G. Treatment with high-dose n-3 PUFAs has no effect on platelet function, coagulation, metabolic status or inflammation in patients with atherosclerosis and type 2 diabetes. Cardiovasc Diabetol. 2017 Apr 14;16(1):50. doi: 10.1186/s12933-017-0523-9.

  PMID: 28410617 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Cardiovascular Diseases

Interventions

Docosahexaenoic Acids

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Fatty Acids, Omega-3; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils

Study Officials

• Grzegorz Gajos, prof.assoc.

  Department of Coronary Disease, Institute of Cardiology, Jagiellonian University Medical College

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: prof.assoc.

Study Record Dates

• First Submitted: April 12, 2014
• First Posted: June 30, 2014
• Study Start: January 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: February 1, 2016
• Last Updated: November 29, 2016

Record last verified: 2016-11

Locations

PL (2)