Fatty Acid Regulation of Platelet Function in Diabetes

NCT ID: NCT02373332

Last Updated: 2021-06-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

90 participants

Study Classification

OBSERVATIONAL

Study Start Date

2013-08-31

Study Completion Date

2019-05-21

Brief Summary

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This study investigates the potential protective effects of altering fatty acid in the platelet as a method for prevention of platelet activation and thrombosis in type 2 diabetes mellitus. Fatty acids (omega-3 and omega-6) and their oxidized lipids will be evaluated for protection from agonist-mediated platelet activation in platelets from type 2 diabetics and healthy controls.

Detailed Description

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12-lipoxygenase and essential fatty acids such as omega-3 and omega-6 have been shown to play important roles in regulating platelet activation, but the underlying mechanisms have not been fully elucidated as well as their true protection from thrombosis.

12-lipoxygenase inhibition prevents platelet activation in part by inhibiting 12-lipoxygenase oxidation of free fatty acids in the platelet. These oxidized fatty acids are known to play both a pro- and anti-thrombotic effect on platelets depending on the fatty acid. oxidation of arachidonic acid by 12-lipoxygenase results in a pro-thrombotic bioactive lipid whereas oxidation of the omega-6 fatty acid DGLA found in plant oil results in formation of a potent anti-thrombotic bioactive lipid. Determining the extent of protection from this and other bioactive lipids produced through 12-lipoxygenase will allow for a better understanding of which fatty acid supplementation may best protect from thrombosis.

Essential fatty acids such as omega-3 (DHA/EPA) and omega-6 (DGLA) appear to be protective. However the underlying mechanism for this potential protection is not well understood. Identifying the mechanism by which these supplements protect from platelet activation may identify new approaches to preventing thrombotic events in this high risk population.

Conditions

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Thrombosis Type 2 Diabetes Mellitus

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Healthy subjects

Healthy subjects for oxylipin effect Platelets from healthy donors will be assessed for regulation of platelet reactivity by fatty acids and 12-lipoxygenase oxylipins.

omega-3 and -6 fatty acids and their 12-LOX oxylipins

Intervention Type OTHER

platelets from healthy subjects and T2DM patients will be isolated from their blood and treated with omega-3 and -6 fatty acids and their 12-LOX oxylipins of those fatty acids followed by assessment of protection from agonist-induced platelet activation and thrombosis

Type 2 diabetes mellitus (T2DM) patients

T2DM patients for oxylipin effect Platelets from healthy donors will be assessed for regulation of platelet reactivity by fatty acids and 12-lipoxygenase oxylipins.

No interventions assigned to this group

Interventions

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omega-3 and -6 fatty acids and their 12-LOX oxylipins

platelets from healthy subjects and T2DM patients will be isolated from their blood and treated with omega-3 and -6 fatty acids and their 12-LOX oxylipins of those fatty acids followed by assessment of protection from agonist-induced platelet activation and thrombosis

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Healthy subjects and T2DM patients
* African American and Caucasian
* T2DM patients on controlled medication (taking metformin)

Exclusion Criteria

* Dietary supplement within 2 weeks of enrollment
* Fish and plant oil supplements 2 months prior to enrollment
* NSAIDS and aspirin 1 week prior to enrollment
* Smoking
* Cardiovascular event within 6 months prior to enrollment
* Other anti-platelet treatment including phosphodiesterase (PDE) and P2Y12R inhibitors
* Estimated Glomerular Filtration Rate (eGFR) below 30 (severe renal insufficiency)
* eGFR above 90
Minimum Eligible Age

21 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

University of Michigan

OTHER

Sponsor Role lead

Responsible Party

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Michael Holinstat

Associate Professor of Pharmacology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michael Holinstat, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

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University of Michigan

Ann Arbor, Michigan, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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R01HL114405

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ODS

Identifier Type: OTHER

Identifier Source: secondary_id

Michigan-114405A

Identifier Type: -

Identifier Source: org_study_id

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