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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02629497
• Other study ID #: HL 114405
• Secondary ID: R01HL114405ODS
• Status: Completed
• Phase: Early Phase 1
• Start date: November 2015
• Est. completion date: June 2017

Study information

• Verified date: July 2021
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 21 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Thrombosis
• Type 2 Diabetes Mellitus

Intervention

Dietary Supplement:
• 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.
• 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.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	platelet reactivity	decreased platelet activity ex vivo translating to protection from clot formation in vivo	through study completion, an average of 1 year
Secondary	fatty acid incorporation	measure altered levels of essential fatty acids in blood and platelets following treatment	through study completion, an average of 1 year
Secondary	Oxylipin production	determine the oxylipin products formed following each intervention	through study completion, an average of 1 year