Fish Oil and Aspirin With Type 2 Diabetes

Cardiovascular Disease Clinical Trial

— R-21  

Official title:

The Effects of Fish Oil and Aspirin on Cardiovascular Risk in Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01181882
• Other study ID #: RSRB00030668
• Status: Completed
• Phase: Phase 2
• First received: August 3, 2010
• Last updated: October 7, 2013
• Start date: August 2010
• Est. completion date: November 2012

Study information

• Verified date: October 2013
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to understand if omega-3 fatty acids in fish oil enhance the ability of aspirin to reduce the risk of cardiovascular diseases such as heart attack and stroke in those who have diabetes mellitus.

Description:

A recent increase in the incidence and prevalence of obesity-related diabetes mellitus and the metabolic syndrome as a result of insulin resistance threatens to reverse the health gains achieved in the US during the last half of the 20th century. Novel inexpensive and safe pharmacologic approaches are required to prevent a variety of resulting cardiovascular disease sequelae. Aspirin is a proven agent in the treatment and prevention of cardiovascular disease but is greatly underused. Even when it is used, aspirin is ineffective in a large proportion of the population: a problem termed "aspirin resistance." Approximately thirty percent of the adult US population is aspirin resistant and this proportion is higher in those with diabetes and the metabolic events and affected patients do not benefit from other antiplatelet drugs. The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are naturally occurring and can be safely used at low cost in individuals who are in high and lower cardiovascular risk groups. Supplementation with EPA and and DHA (EPA + DHA) modifies the fatty acid balance which is distributed in patients with insulin resistance and atherosclerosis, thereby potentially improving endothelial function, lowering blood pressure, and reducing the risk of fatal and non-fatal acute coronary syndromes. Emerging evidence indicates that the combination of aspirin together with EPA+DHA supplementation beneficially regulates fatty acid metabolism and attenuates atherosclerosis. However, the effects of aspirin together with EPA + DHA on aspirin resistance or in subjects with diabetes mellitus and insulin resistance are unknown. Circulating EPA and DHA are contained largely in lysophospholipids, which contain a three carbon backbone and variable fatty acyl side chains. In preliminary data, we show that both aspirin ingestion and EPA+DHA supplementation after lysophospholipids including lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA) are now known to bind specific G-protein coupled receptors, which are being explored as novel therapeutic targets in cardiovascular and other diseases. Relationships between LPC and LPA metabolism, aspirin ingestion, and human atherosclerosis have not been investigated (to our knowledge). In the proposed study, we will investigate the effects of combining aspirin with EPA+DHA supplementation on platelet function and lysophospholipid metabolism in a clinical trial of individuals with type 2 diabetes mellitus. This trial will build on existing infrastructure in clinical and translational research, as well as our preliminary data using novel in-house assays.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• Between the ages of 40-80

• No significant abnormality noted from the CBC, CMP, TSH

• Have diabetes mellitus based on the criteria from the Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. (57) These data will be collected from medical records in conjunction with the Greater Rochester Practice-Based Research Network (see recruitment plan below)

1. Symptoms of diabetes plus casual plasma glucose concentration greater than or equal to 200 mg/dl (11.1 mmol/l). Casual is defined as any time of day without regard to last time since last meal. The classic symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss, or;

2. Fasting plasma glucose greater than or equal to 126 mg/dl (11.1 mmol/l). Fasting is defined as no caloric intake for at least 8 h, or;

3. 2-hour plasma glucose greater than or equal to 200 mg/dl (11.1 mmol/l) during an oral glucose tolerance test. The test should be performed as described by the World Health organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water. This is the protocol within the University of Rochester Clinical Labs.

(In the absence of unequivocal hyperglycemia with acute metabolic decompensation, these criteria should have been confirmed by repeat testing on a different day)

• Available for two morning visits (5 hours at bedrest) approximately 28 days apart and 2 short visits for blood draws

• No fish oil, flax seed oil, vitamins, nutri. supplements or herbal preps. during study

• Able to commit to no aspirin, NSAIDS for 10 days prior to each 5-hour study visit

• Able to commit to no more then 2 meals of fish 7 days prior to each visit

• Non-smoker

• Not currently pregnant, and will not become pregnant during study

Exclusion Criteria:

• History of drug or alcohol abuse, or current weekly alcohol consumption >14 units/week (1 unit=1 beer, 1 glass of wine, 1 mixed cocktail containing 1 ounce of alcohol)

• Diagnosis of cardiovascular disease including coronary heart disease, congestive heart failure, peripheral vascular disease, stroke, atrial fibrillation, and gastric bypass surgery or malabsorption syndrome.

• History of malignancy (unless disease free for >10 years, or non-melanoma skin carcinoma)

• History of peptic ulcer or gastrointestinal bleeding in past 5 years

• Diagnosed bleeding disorder

• Use of antiplatelet or antithrombotic therapy, defined as clopidogrel, ticlopidine, cilostazol, dipyridamol, trapidil, warfarin, and argatroban

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Dietary Supplement:
• Fish Oil and Aspirin
4 grams of fish oil each day for 28 days and 81 mg aspirin

Locations

Country	Name	City	State
United States	Clinical Research Center of the University of Rochester Medical Center	Rochester	New York

Sponsors (3)

Lead Sponsor	Collaborator
University of Rochester	Albany College of Pharmacy and Health Sciences, Cornell University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Platelet function	Platelet function effect will be measured with aspirin alone and 4 hours later, after fish oil ingestion.	4 hours	No
Secondary	Lysophospholipids	Plasma measurement of lysophospholipids will be measured with aspirin alone and 4 hours later, after fish oil ingestion. These analyses will be considered exploratory due to the fact that no previous data exist regarding the relationships investigated and multiple testing is inherent to these analyses as 11 species of each LPA and LPC will be measured.	4 hours	No