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

Early Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus; Thrombosis
• Interventions: Dietary Supplement: Primrose oil; Dietary Supplement: Fish Oil

• Registration Number: NCT02629497
• Lead Sponsor: University of Michigan

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2015-01-14
• Study Start: 2015-11
• Study First Submitted QC: 2015-12-09
• Study First Posted: 2015-12-14
• Primary Completion: 2017-06
• Study Completion: 2017-06
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-28
• Last Update Posted: 2021-08-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 90

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
T2DM patients for Omega-6 protection	Primrose oil	platelets from Type 2 diabetes mellitus (T2DM) patients will be assessed for regulation by Primrose Oil (omega-6 fatty acid).
Healthy control for Omega-3 protection	Fish Oil	Platelets from healthy donors will be assessed for regulation by Fish Oil (omega-3 fatty acid).
Healthy subjects for Omega-6 protection	Primrose oil	Platelets from healthy donors will be assessed for regulation by Primrose Oil (omega-6 fatty acid).
T2DM for Omega-3 protection	Fish Oil	platelets from Type 2 diabetes mellitus (T2DM) patients will be assessed for regulation by Fish Oil (omega-3 fatty acid).

Primary Outcome Measures

Name	Time	Method
platelet reactivity	through study completion, an average of 1 year	decreased platelet activity ex vivo translating to protection from clot formation in vivo

Secondary Outcome Measures

Name	Time	Method
fatty acid incorporation	through study completion, an average of 1 year	measure altered levels of essential fatty acids in blood and platelets following treatment
Oxylipin production	through study completion, an average of 1 year	determine the oxylipin products formed following each intervention

Trial Locations

Locations (1)

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States