search
Back to results

Effects of Eicosapentaenoic Acid on Endothelial Function in Diabetic Subjects

Primary Purpose

Type 2 Diabetes, Coronary Artery Disease

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Icosapent ethyl
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Type 2 Diabetes focused on measuring Endothelial function, Eicosapentaenoic acid, Triglycerides

Eligibility Criteria

30 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Brigham and Women's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

EPA arm

Control

Arm Description

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

Control group will not receive EPA

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).

Full Information

First Posted
April 14, 2015
Last Updated
February 22, 2022
Sponsor
Brigham and Women's Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT02422446
Brief Title
Effects of Eicosapentaenoic Acid on Endothelial Function in Diabetic Subjects
Official Title
Effects of Eicosapentaenoic Acid on Endothelial Function in Diabetic Subjects: A Pilot Trial
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Terminated
Why Stopped
Difficulty enrolling patients with elevated triglycerides under statin treatment
Study Start Date
April 2015 (undefined)
Primary Completion Date
March 1, 2017 (Actual)
Study Completion Date
March 1, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes, Coronary Artery Disease
Keywords
Endothelial function, Eicosapentaenoic acid, Triglycerides

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EPA arm
Arm Type
Experimental
Arm Description
EPA arm will receive 4 grams per day of EPA (icosapent ethyl) taken twice a day
Arm Title
Control
Arm Type
No Intervention
Arm Description
Control group will not receive EPA
Intervention Type
Drug
Intervention Name(s)
Icosapent ethyl
Other Intervention Name(s)
Vascepa, Eicosapentaenoic Acid, EPA
Intervention Description
icosapent ethyl is eicosapentaenoic acid, an omega-3 fatty acid that naturally occurs in fish
Primary Outcome Measure Information:
Title
Change From Baseline in Endothelial Function at 12 Weeks Using Reactive Hyperemia Index (RHI)
Description
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
Secondary Outcome Measure Information:
Title
Change in Endothelin-1 (ET-1), High-sensitive C-reactive Protein (hsCRP), and Oxidized LDL Between Baseline and 12 Weeks
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02120
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Effects of Eicosapentaenoic Acid on Endothelial Function in Diabetic Subjects

We'll reach out to this number within 24 hrs