Role of 12-lipoxygenase in Platelet Reactivity and Type 2 Diabetes Mellitus

NCT ID: NCT02629497

Last Updated: 2025-05-30

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

Clinical Phase

EARLY_PHASE1

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2017-06-30

Brief Summary

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This study investigates the potential protective effects of fatty acid supplementation through inhibition of platelet activation. fatty acids (omega-3 and omega-6) will be evaluated for protection from agonist-mediated platelet activation in platelets from type 2 diabetics and healthy controls. Post-menopausal women with type 2 diabetes mellitus and healthy post-menopausal women will be treated with omega-3 and omega-6 fatty acid supplements to determine protection from platelet activation and thrombosis in this high risk population.

Detailed Description

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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 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 resuts 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 oxygenase activity 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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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Healthy subjects for Omega-6 protection

Platelets from healthy donors will be assessed for regulation by Primrose Oil (omega-6 fatty acid).

Group Type EXPERIMENTAL

Primrose oil

Intervention Type DIETARY_SUPPLEMENT

T2DM patients and matched controls subjects will be given Primrose oil for 2 months, followed by 2-week washout. Blood will be drawn at the beginning, during, and following treatments and platelet function will be assessed.

T2DM patients for Omega-6 protection

platelets from Type 2 diabetes mellitus (T2DM) patients will be assessed for regulation by Primrose Oil (omega-6 fatty acid).

Group Type EXPERIMENTAL

Primrose oil

Intervention Type DIETARY_SUPPLEMENT

T2DM patients and matched controls subjects will be given Primrose oil for 2 months, followed by 2-week washout. Blood will be drawn at the beginning, during, and following treatments and platelet function will be assessed.

Healthy control for Omega-3 protection

Platelets from healthy donors will be assessed for regulation by Fish Oil (omega-3 fatty acid).

Group Type ACTIVE_COMPARATOR

Fish Oil

Intervention Type DIETARY_SUPPLEMENT

T2DM patients and matched controls subjects will be given Fish oil for 2 months, followed by 2-week washout. Blood will be drawn at the beginning, during, and following treatments and platelet function will be assessed.

T2DM for Omega-3 protection

platelets from Type 2 diabetes mellitus (T2DM) patients will be assessed for regulation by Fish Oil (omega-3 fatty acid).

Group Type ACTIVE_COMPARATOR

Fish Oil

Intervention Type DIETARY_SUPPLEMENT

T2DM patients and matched controls subjects will be given Fish oil for 2 months, followed by 2-week washout. Blood will be drawn at the beginning, during, and following treatments and platelet function will be assessed.

Interventions

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Primrose oil

T2DM patients and matched controls subjects will be given Primrose oil for 2 months, followed by 2-week washout. Blood will be drawn at the beginning, during, and following treatments and platelet function will be assessed.

Intervention Type DIETARY_SUPPLEMENT

Fish Oil

T2DM patients and matched controls subjects will be given Fish oil for 2 months, followed by 2-week washout. Blood will be drawn at the beginning, during, and following treatments and platelet function will be assessed.

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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DHA/EPA

Eligibility Criteria

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Inclusion Criteria

* Healthy subjects and T2DM patients
* Postmenopausal women with T2DM
* All races and ethnicities
* T2DM patients taking 1st line diabetic treatment (i.e. Metformin)

Exclusion Criteria

* Fish and plant oil supplements 2 months prior to enrollment
* NSAIDS and aspirin 1 week prior to enrollment
* Cardiovascular event within 6 months prior to enrollment
* Other anti-platelet treatment including PDE and P2Y12 inhibitors
Minimum Eligible Age

21 Years

Maximum Eligible Age

70 Years

Eligible Sex

FEMALE

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

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michael A Holinstat, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

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University of Michigan

Ann Arbor, Michigan, United States

Site Status

Countries

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United States

References

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Yamaguchi A, Stanger L, Freedman JC, Prieur A, Thav R, Tena J, Holman TR, Holinstat M. Supplementation with omega-3 or omega-6 fatty acids attenuates platelet reactivity in postmenopausal women. Clin Transl Sci. 2022 Oct;15(10):2378-2391. doi: 10.1111/cts.13366. Epub 2022 Jul 25.

Reference Type BACKGROUND
PMID: 35791734 (View on PubMed)

Other Identifiers

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R01HL114405

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ODS

Identifier Type: OTHER

Identifier Source: secondary_id

HL 114405

Identifier Type: -

Identifier Source: org_study_id

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