Coronary Artery Disease, Type 2 Diabetes
Conditions
Keywords
Endothelial function, Eicosapentaenoic acid, Triglycerides
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.
Interventions
DRUGIcosapent ethyl
icosapent ethyl is eicosapentaenoic acid, an omega-3 fatty acid that naturally occurs in fish
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EPA Arm EPA arm will receive 4 grams per day of EPA (icosapent ethyl) taken twice a day
Icosapent ethyl: icosapent ethyl is eicosapentaenoic acid, an omega-3 fatty acid that naturally occurs in fish | 1 |
| Control Control group will not receive EPA | 1 |
| Total | 2 |
Baseline characteristics
| Characteristic | EPA Arm | Total | Control |
|---|---|---|---|
| Age, Continuous | 69 years | 63 years | 57 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants |
| Triglycerides | 221 mg/dl | 199 mg/dl | 177 mg/dl |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Change From Baseline in Endothelial Function at 12 Weeks Using Reactive Hyperemia Index (RHI)
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.
Time frame: Between baseline and 12 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| EPA Arm | Change From Baseline in Endothelial Function at 12 Weeks Using Reactive Hyperemia Index (RHI) | -29 % change from baseline value |
| Control | Change From Baseline in Endothelial Function at 12 Weeks Using Reactive Hyperemia Index (RHI) | -1.6 % change from baseline value |
Secondary
Change in Endothelin-1 (ET-1), High-sensitive C-reactive Protein (hsCRP), and Oxidized LDL Between Baseline and 12 Weeks
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).
Time frame: change between baseline and 12 weeks post-intervention
Population: Because the trial was terminated prematurely due to difficulties in finding suitable subjects, we were not able to measure any of the three biomarkers specified under the secondary outcome (ET-1, hsCRP, and Oxidized LDL).