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

University of Michigan

Status and phase: Completed; Early Phase 1

Conditions: Thrombosis; Type 2 Diabetes Mellitus

Treatments: Dietary Supplement: Fish Oil; Dietary Supplement: Primrose oil

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02629497

ODS (Other Identifier)

HL 114405

R01HL114405 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 90 patients

Sex: Female

Ages: 21 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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90 participants in 4 patient groups

Healthy subjects for Omega-6 protection

Experimental group

Description:

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

Treatment:

Dietary Supplement: Primrose oil

T2DM patients for Omega-6 protection

Experimental group

Description:

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

Treatment:

Dietary Supplement: Primrose oil

Healthy control for Omega-3 protection

Active Comparator group

Description:

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

Treatment:

Dietary Supplement: Fish Oil

T2DM for Omega-3 protection

Active Comparator group

Description:

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

Treatment:

Dietary Supplement: Fish Oil