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

July 28, 2021 updated by: Michael Holinstat, University of Michigan
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

90

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Healthy subjects for Omega-6 protection
Platelets from healthy donors will be assessed for regulation by Primrose Oil (omega-6 fatty acid).
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.
Experimental: 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).
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.
Active Comparator: Healthy control for Omega-3 protection
Platelets from healthy donors will be assessed for regulation by Fish Oil (omega-3 fatty acid).
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.
Other Names:
  • DHA/EPA
Active Comparator: 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).
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.
Other Names:
  • DHA/EPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
platelet reactivity
Time Frame: through study completion, an average of 1 year
decreased platelet activity ex vivo translating to protection from clot formation in vivo
through study completion, an average of 1 year

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Michael A Holinstat, PhD, University of Michigan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2015

Primary Completion (Actual)

June 1, 2017

Study Completion (Actual)

June 1, 2017

Study Registration Dates

First Submitted

January 14, 2015

First Submitted That Met QC Criteria

December 9, 2015

First Posted (Estimate)

December 14, 2015

Study Record Updates

Last Update Posted (Actual)

August 4, 2021

Last Update Submitted That Met QC Criteria

July 28, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HL 114405
  • R01HL114405 (U.S. NIH Grant/Contract)
  • ODS (Other Identifier: Office of Dietary Supplementation (NIH), co-funder)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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