ThrombosisEarly Phase 1NCT02629497
Role of 12-lipoxygenase in Platelet Reactivity and Type 2 Diabetes Mellitus
A Early Phase 1 study testing Primrose oil and Fish Oil in people with Thrombosis and Type 2 Diabetes Mellitus, run by University of Michigan at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 21 to 70 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Thrombosis, Type 2 Diabetes Mellitus
- What is being tested?
- Primrose oil and Fish Oil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to Jun 2017
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy subjects and T2DM patients
- Postmenopausal women with T2DM
- All races and ethnicities
- T2DM patients taking 1st line diabetic treatment (i.e. Metformin)
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Thrombosis, Type 2 Diabetes Mellitus
- Being tested
- Primrose oil, Fish Oil
- Keywords
- platelets, 12-lipoxygenase, fatty acids, DGLA, DHA, EPA, 12-LOX
- Medical subject headings
- Thrombosis, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Primrose oilDietary supplement
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 OilDietary supplement
Also called DHA/EPA
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.
| Study group | Role | What they receive |
|---|---|---|
| Healthy subjects for Omega-6 protection | Experimental | Platelets from healthy donors will be assessed for regulation by Primrose Oil (omega-6 fatty acid). Receives: Dietary Supplement: Primrose oil |
| T2DM patients for Omega-6 protection | Experimental | platelets from Type 2 diabetes mellitus (T2DM) patients will be assessed for regulation by Primrose Oil (omega-6 fatty acid). Receives: Dietary Supplement: Primrose oil |
| Healthy control for Omega-3 protection | Active comparator | Platelets from healthy donors will be assessed for regulation by Fish Oil (omega-3 fatty acid). Receives: Dietary Supplement: Fish Oil |
| T2DM for Omega-3 protection | Active comparator | platelets from Type 2 diabetes mellitus (T2DM) patients will be assessed for regulation by Fish Oil (omega-3 fatty acid). Receives: Dietary Supplement: Fish Oil |
What is being measured
The primary outcome is the main question the study is designed to answer.
platelet reactivity
decreased platelet activity ex vivo translating to protection from clot formation in vivo
Measured: through study completion, an average of 1 year
Secondary outcomes (2)
fatty acid incorporation
measure altered levels of essential fatty acids in blood and platelets following treatment
Measured: through study completion, an average of 1 year
Oxylipin production
determine the oxylipin products formed following each intervention
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2015 (estimated)
- Study startNov 2015
- Primary completionJun 2017
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ThrombosisStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Michael Holinstat, University of Michigan
- Investigators
- Michael A Holinstat, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02629497
- Sponsor's protocol ID
- HL 114405
- Other IDs
- R01HL114405, ODS
- Status last verified
- May 2025
- First submitted
- 14 Jan 2015
- Last updated
- 30 May 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 35791734
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of 12-lipoxygenase in Platelet Reactivity and Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT02629497
- Acronym / sponsor ID
- HL 114405
- Conditions
- Thrombosis, Type 2 Diabetes Mellitus
- Keywords
- platelets, 12-lipoxygenase, fatty acids, DGLA, DHA, EPA, 12-LOX
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Nov 2015
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 14 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Healthy subjects for Omega-6 protection | Experimental | Dietary Supplement: Primrose oilPlatelets from healthy donors will be assessed for regulation by Primrose Oil (omega-6 fatty acid). |
| T2DM patients for Omega-6 protection | Experimental | Dietary Supplement: Primrose oilplatelets 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 | Active comparator | Dietary Supplement: Fish OilPlatelets from healthy donors will be assessed for regulation by Fish Oil (omega-3 fatty acid). |
| T2DM for Omega-3 protection | Active comparator | Dietary Supplement: Fish Oilplatelets from Type 2 diabetes mellitus (T2DM) patients will be assessed for regulation by Fish Oil (omega-3 fatty acid). |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Healthy subjects and T2DM patients
- Postmenopausal women with T2DM
- All races and ethnicities
- T2DM patients taking 1st line diabetic treatment (i.e. Metformin)
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Primrose oilT2DM 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. | Dietary supplement | Healthy subjects for Omega-6 protection, T2DM patients for Omega-6 protection |
| Fish OilAlso: DHA/EPAT2DM 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. | Dietary supplement | Healthy control for Omega-3 protection, T2DM for Omega-3 protection |
Primary outcome
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
2 secondary outcomes
fatty acid incorporation
Time frame: through study completion, an average of 1 year
Oxylipin production
Time frame: through study completion, an average of 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2025.
- Results publication: PubMed 35791734Yamaguchi 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.
- Individual participant dataSharing planned: No
Related trials for Thrombosis
Not yet recruitingPhase 3
TicAgreLor Versus Placebo to Prevent Cerebral ISCHemia in anEuRysmal Low Grade SAH A Double Blinded Randomised Controlled Study
Subarachnoid Hemorrhage, Aneurysmal, Brain Ischemia
RecruitingObservational study
Study of the Long-Term Safety and Outcomes of Treating Pulmonary Embolism With the Indigo Aspiration System
Pulmonary Embolism
RecruitingPhase 2
SBRT With Immunotherapy and Atezo-Bev in HCC With Major Portal Vein Thrombosis
HCC
Not yet recruiting
Pilot Study Evaluating Catheter Directed Thrombolysis Device in Acute Intermediate Risk Pulmonary Embolism
Pulmonary Embolism (PE), Pulmonary Embolism With Right Ventricle Enlargement
Active, not recruitingObservational study
Real World Evidence in China: Faricimab Use in Diabetic Macular Edema, Retinal Vein Occlusion, and Neovascular Age-Related Macular Degeneration (The Farseeing Study)
Diabetic Macular Edema, Neovascular Age-related Macular Degeneration
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael A Holinstat, PhD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Primrose oil and Fish Oil in people with Thrombosis and Type 2 Diabetes Mellitus, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
platelet reactivity (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02629497, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2025.