Clinical trial NCT02629497: Role of 12-lipoxygenase in Platelet Reactivity and Type 2 Diabetes Mellitus
Official title: Role of 12-lipoxygenase in Platelet Reactivity and Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Thrombosis
Type 2 Diabetes Mellitus
Keywords: platelets
12-lipoxygenase
fatty acids
DGLA
DHA
EPA
12-LOX
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2015-12-14
Enrollment: 90
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: platelet reactivity
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: fatty acid incorporation
timeFrame: through study completion, an average of 1 year
measure: Oxylipin production
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Michael A Holinstat, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.