Effects of Eicosapentaenoic Acid on Endothelial Function in Diabetic Subjects

Phase 3

Terminated

Brief Summary: This pilot trial seeks to obtain preliminary data on the effects of eicosapentaenoic acid (EPA) (4g/d) on endothelial function measured via endopat2000 after 12 weeks of intervention among adults with elevated triglycerides and type 2 diabetes.

Detailed Description: Thirty adults aged 30-75 y will be randomized to either 4 g/d of eicosapentaenoic acid or no drug for 12 weeks. Endothelial function will be measured at baseline and after 12 weeks. in a secondary aims, we will evaluate effects of eicosapentaenoic acid (EPA) on plasma levels of c-reactive protein, oxidized low-density lipoprotein cholesterol, and endothelin-1.

Recruitment & Eligibility

Inclusion Criteria

Age 30+ years
Hypertriglyceridemia (150-400 mg/dl)
Statin use for at least six months at the time of screening
Type 2 diabetes treated with diet and/or oral hypoglycemic agents diagnosed 1+ year
Ability to provide informed consent and provide blood samples
Willingness to abstain from fish oil, EPA, over the counter niacin, and other omega-3 fatty acid supplements during the study period (12 weeks)
Ability to travel to the study site at Brigham and Women's Hospital for 3 study visits
Reactive hyperemia index (RHI) of ≤ 2.0

Exclusion Criteria

Eating disorder or heavy drinkers
Treatment with chronic prescription pharmacotherapy for metabolic or cardiovascular disease management or risk factor modification
Pregnant or lactating women
Statin use <6 months at the time of screening
Allergy to EPA, fish oil, or other omega-3 fatty acids
Current use of insulin, cyclophosphamide, estrogen, fibrates, niacin, hormone replacement therapy, testosterone, oral contraceptives, growth hormones, insulin-like growth factor-1, and other systemic steroids.
Inability to provide informed consent or blood samples
History or prevalent diagnosis of cancer, asthma, kidney insufficiency, stroke, seizures, allergic disorders, or congestive heart failure
Diagnosis of diabetes < 1 year prior to enrollment
Intention to move out of greater Boston area within one year
Current use of omega-3 supplements, fish oil, or >2 servings of fish per week
Bleeding disorder or uncontrolled endocrine (i.e., thyroid) or metabolic disorders
Treatment with blood thinning drugs (i.e. warfarin and clopidogrel)
Major surgical operation 3 months before or after screening
Organ transplantation
Current participation in another trial or plan to do so during the study
Inability to give informed consent or to travel to the study center at Brigham and Women's Hospital
RHI of >2.0
Triglycerides <150 mg/dl or >400 mg/dl
Body mass index of 40+ kg/m2

Arm && Interventions

Group	Intervention	Description
EPA arm	Icosapent ethyl	EPA arm will receive 4 grams per day of EPA (icosapent ethyl) taken twice a day

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Endothelial Function at 12 Weeks Using Reactive Hyperemia Index (RHI)	Between baseline and 12 weeks	Digital pulse amplitude will be measured with a fingertip peripheral arterial tonometry (PAT) device (Endo-PAT2000, Itamar Medical) in a supine position. Baseline pulse amplitude will be measured for 5 minutes, then the arterial flow will then be interrupted for 5 minutes with a cuff placed on a proximal forearm. Pulse amplitude will be recorded electronically and analyzed by a computerized and automated algorithm. The change from the baseline measurement will be expressed as the reactive hyperemia index (RHI). We will calculate the pulse amplitude response to hyperemia for each 30-second interval as a ratio of the post-deflation pulse amplitude to the baseline pulse amplitude as described previously. The RHI ratio will be computed by dividing the ratio obtained on the test side over the ratio from the control finger. We will assess change in RHI ratio between baseline value and 12-week value after the intervention.

Secondary Outcome Measures

Name	Time	Method
Change in Endothelin-1 (ET-1), High-sensitive C-reactive Protein (hsCRP), and Oxidized LDL Between Baseline and 12 Weeks	change between baseline and 12 weeks post-intervention	Plasma hsCRP will be measured by Sandwich enzyme linked immunosorbent assay (ELISA). Plasma oxidized LDL and plasma ET-1 will be measured using a commercially available sandwich-enzyme immunoassay kit (R \& D).