Effects of Eicosapentaenoic Acid on Endothelial Function in Diabetic Subjects

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02422446
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arms: 2
• Duration (Months): 23
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes; Coronary Artery Disease	Drug: Icosapent ethyl	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Prevention
• Official Title: Effects of Eicosapentaenoic Acid on Endothelial Function in Diabetic Subjects: A Pilot Trial
• Study Start Date: Apr 1, 2015
• Actual Primary Completion Date: Mar 1, 2017
• Actual Study Completion Date: Mar 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EPA arm EPA arm will receive 4 grams per day of EPA (icosapent ethyl) taken twice a day	Drug: Icosapent ethyl; icosapent ethyl is eicosapentaenoic acid, an omega-3 fatty acid that naturally occurs in fish; Other Names: Vascepa Eicosapentaenoic Acid EPA
No Intervention: Control Control group will not receive EPA

Outcome Measures

Primary Outcome Measures

1. 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

1. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02120

Sponsors and Collaborators

• Brigham and Women's Hospital

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 22, 2016
• Informed Consent Form - May 28, 2015

More Information

Publications

None provided.

• Responsible Party: Luc Djousse, Director of Research, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT02422446
• Other Study ID Numbers: 2013D003968
• First Posted: Apr 21, 2015
• Last Update Posted: Mar 18, 2022
• Last Verified: Feb 1, 2022

• Keywords provided by Luc Djousse, Director of Research, Brigham and Women's Hospital: Endothelial function; Eicosapentaenoic acid; Triglycerides
• Additional relevant MeSH terms: Coronary Artery Disease; Eicosapentaenoic acid ethyl ester

Study Results

Participant Flow

Arm/Group Title	EPA Arm	Control
Arm/Group Description	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	Control group will not receive EPA
Period Title: Overall Study
STARTED	1	1
COMPLETED	1	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	EPA Arm	Control	Total
Arm/Group Description	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	Control group will not receive EPA	Total of all reporting groups
Overall Participants	1	1	2
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	69	57	63
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	1 100%	1 100%	2 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	1 100%	1 100%	2 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Triglycerides (mg/dl) [Mean (Full Range) ]
Mean (Full Range) [mg/dl]	221	177	199

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EPA Arm	Control
Arm/Group Description	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	Control group will not receive EPA
Measure Participants	1	1
Mean (Full Range) [% change from baseline value]	-29	-1.6

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	EPA Arm	Control
Arm/Group Description	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	Control group will not receive EPA
Measure Participants	0	0

Adverse Events

Time Frame	Total study period of 12 weeks
Arm/Group Title	EPA Arm		Control
Arm/Group Description	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		Control group will not receive EPA
All Cause Mortality
	EPA Arm		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Serious Adverse Events
	EPA Arm		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	EPA Arm		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.