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Fatty Acid Regulation of Platelet Function in Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02373332
Recruitment Status : Active, not recruiting
First Posted : February 27, 2015
Last Update Posted : June 1, 2020
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Michael Holinstat, University of Michigan

Brief Summary:
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.

Condition or disease Intervention/treatment
Thrombosis Type 2 Diabetes Mellitus Other: omega-3 and -6 fatty acids and their 12-LOX oxylipins

Detailed Description:

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.

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Fatty Acid Regulation of Platelet Function in Diabetes
Study Start Date : August 2013
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Clots

Group/Cohort Intervention/treatment
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.
Other: 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

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.



Primary Outcome Measures :
  1. inhibition of platelet activation [ Time Frame: one-time blood draw ]
    following blood draw, the ability of fatty acids or their oxylipins to inhibit platelet activation will be assessed.


Biospecimen Retention:   Samples With DNA
Platelets, plasma, and whole blood will be assessed for platelet reactivity and thrombosis and stored for later analysis of protein expression. DNA will be stored for assessment of levels of gene products throught to play a role in platelet reactivity.


Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Adults ages 21-70. Both female and male and no preference for race or ethnicity. Subjects will abstain from anti-platelet therapy for 10 days. Health status will be confirmed by oral questioning and written questionnaire and confirmed following blood draw prior to evaluation of platelets with fatty acid or oxylipins.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02373332


Locations
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United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
University of Michigan
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Michael Holinstat, PhD University of Michigan
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Responsible Party: Michael Holinstat, Associate Professor of Pharmacology, University of Michigan
ClinicalTrials.gov Identifier: NCT02373332    
Other Study ID Numbers: Michigan-114405A
R01HL114405 ( U.S. NIH Grant/Contract )
ODS ( Other Identifier: Office of Dietary Supplementation (NIH), co-funder )
First Posted: February 27, 2015    Key Record Dates
Last Update Posted: June 1, 2020
Last Verified: May 2020
Keywords provided by Michael Holinstat, University of Michigan:
platelets
12-lipoxygenase
fatty acids
DGLA
DHA
EPA
12-LOX
Additional relevant MeSH terms:
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Thrombosis
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases