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Coronary Heart DiseaseHEARTSNCT01624727

Slowing HEART diSease With Lifestyle and Omega-3 Fatty Acids

A study testing Omega 3 acid ethyl esters in people with Coronary Heart Disease and Metabolic Syndrome, run by Beth Israel Deaconess Medical Center at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of the study is to target inflammation to reduce progression of noncalcified plaque in the coronary arteries using omega-3 fatty acid supplementation compared to standard of care. Read more about this study

Who is it for?
Ages 21 to 80 years
Conditions the study is for
Coronary Heart Disease, Metabolic Syndrome
What is being tested?
Omega 3 acid ethyl esters
Could I receive a placebo?
No, everyone receives an active treatment
How many people
338 participants
Where
2 sitesUnited States
Study dates
Jun 2009to 15 Jan 2015
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • coronary artery disease
  • previous myocardial infarction
  • angioplasty (> 6 months ago)
  • previous coronary bypass surgery (> 12 months ago)
  • stable angina
  • non-calcified plaque on prior CT
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  • abnormal exercise tolerance test
  • aged 21- 80 years
  • BMI ≥ 27 kg/m2 and ≤ 35 kg/m2 if female and ≤ 40 kg/m2 if male (a BMI > 24.5 for subjects from Asian origin)
  • stable dose of statin for 1 month at screening or unable to tolerate a statin
  • normal renal function - estimated creatinine clearance calculated using Cockcroft-Gault (CG) equation ≥60 at screening [eCrCLCG (ml/min) = [(140 - age) x weight (kg)]/[SCr(mg/dl) x 72] x [0.85 if female] or serum Cr < 1.3
  • ALT, AST) < 3 times upper limits of normal)
  • normal thyroid function or on stable dose replacement therapy
  • an ETT performed within 12 months prior

Who cannot join

  • unstable angina (increase in frequency or severity of anginal episodes or development of chest pain at rest)
  • significant obstructive disease in left main coronary artery, ostial LAD or newly diagnosed three-vessel disease since prior cardiac catheterization by MDCTA
  • significant heart failure (NYHA class III and IV)
  • Current atrial fibrillation or Wolf-Parkinson-White (WPW) syndrome
  • allergy to beta-blocker in subjects with resting heart rate > 65 bpm
  • systolic blood pressure > 160 mm Hg
Show all 27Show fewer
  • diastolic BP > 100 mm Hg
  • persons with allergies to iodinated contrast material or shellfish
  • allergy to nitroglycerin
  • history of asthma only if unable to tolerate beta-blockers
  • BMI > 35 kg/m2 if female and > 40 kg/m2 if male
  • body weight > 350 lbs
  • Use of drugs for weight loss [eg Xenical (orlistat), Meridia (sibutramine), Acutrim (phenylpropanolamine) or similar over-the-counter medications] within three months of screening
  • surgery within 30 days of screening
  • history of acquired immune deficiency syndrome or human immunodeficiency virus (HIV)
  • poor mental function or history of dementia/Alzheimer's Disease or on medications used for treatment of dementia [e.g. Tacrine (Cognex), Rivastigmine (Exelon), Galantamine (Razadyne, Reminyl), Donepezil (Aricept), Memantine (Namenda)] or any other reason to except patient difficulty in complying with the requirements of the study
  • medicine for erectile dysfunction within 72 hours prior to MDCTA
  • Prior stroke with residual cognitive deficit or functional deficit preventing any type of exercise
  • Current chemotherapy or radiation for malignancy
  • Current weekly alcohol consumption > 21 units/week (1 unit = 1 beer, 1 glass of wine, 1 mixed cocktail containing 1 ounce of alcohol)
  • Exclusions based on nuclear imaging:
  • Transient cavity dilation
  • More than one vascular territory involved with reversible defect (multiple defects)
  • Reversible defects involving the anterior wall, septum or apex (LAD territory)
  • Exclusions based on echocardiography imaging:
  • 1. More than one vascular territory involved with inducible wall motion abnormalities (multiple defects) 2. Inducible wall motion abnormalities involving the anterior wall, septum or apex (LAD territory)
  • -

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • South Shore Medical Group

    Milton, Massachusetts, 02186

Other trials in United States

About this study

Official title: Slowing HEART diSease With Lifestyle and Omega-3 Fatty Acids (HEARTS)

The purpose of the study is to target inflammation to reduce progression of noncalcified plaque in the coronary arteries using omega-3 fatty acid supplementation compared to standard of care.

Read the detailed description

Study Design: This is a randomized, parallel study design with a usual care control group. 278 subjects with coronary heart disease (CHD) are being randomized to omega-3 supplementation or standard of care (139 in each arm).

Multidetector computed tomographic angiography (MDCTA) is performed at baseline to quantitate the amount of noncalcified and calcified coronary plaque and again at 30 month follow-up to determine if there has been a change in the volume of noncalcified or total plaque. The primary endpoint is change in coronary noncalcified plaque volume during the 30 months of intervention between active and standard of care.

Hypothesis: Percent change in progression of coronary plaque volume will be less for the omega-3 fatty acid intervention compared to standard of care.

Secondary endpoints include plasma levels of inflammatory markers, lipids and measures of insulin sensitivity.

Secondary outcomes include testing the hypothesis that targeting inflammation with omega-3 fatty acids will be associated with:

  1. Change in total plaque volume per patient.
  2. improvement in physical function and exercise and reduction in pain and stiffness as measured by the WOMAC questionnaire
  3. Reduction of mediators of inflammation in the circulation including CRP, PAI-1, serum amyloid A, MMP-9 and fibrinogen, pro-inflammatory cytokines including IL-6, TNF-a and IL-1b, the adhesion molecules VCAM-1 and ICAM-1, increase in adiponectin and reduction in serum nitrotyrosine as a marker of oxidative stress.
  4. Reduction of insulin resistance assessed by fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR).
  5. Reduction of inflammation in the liver associated with nonalcoholic steatohepatitis (NASH), a newly recognized component of the metabolic syndrome, and reduction of fatty liver quantitated by computerized tomography and levels of AST and ALT as markers of liver inflammation related to NASH.
  6. Investigation of the relationship between vitamin D status and coronary plaque progression as well as with insulin resistance (HOMA-IR), beta-cell function (HOMA-%beta) and inflammatory cytokines.
  7. Determination of whether baseline vitamin D levels predict clinical response to the omega-3 fatty acid intervention, and whether hypovitaminosis D is associated with plaque progression.
Being tested
Omega 3 acid ethyl esters
Keywords
Coronary heart disease, metabolic syndrome, CT angiography
Medical subject headings
Coronary Disease, Metabolic Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Omega 3 acid ethyl estersDietary supplement

    Lovaza 3.6 g daily

Study groups in NCT01624727
Study groupRoleWhat they receive
Usual careNo interventionThose randomized to usual care will continue to follow the care provided by their cardiologist. They will have all the follow-up phone calls, visits and testing which the intervention group has.
Lovaza (Omega 3 ethyl esters)Active comparatorNot described
Receives: Dietary Supplement: Omega 3 acid ethyl esters

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The primary endpoint is change in coronary noncalcified plaque volume.

    MDCTA is performed at baseline to quantitate the amount of noncalcified and calcified coronary plaque and again at 30 month follow-up to determine if there has been a change in the volume of noncalcified or total plaque. The primary endpoint is change in coronary noncalcified plaque volume during the 30 months of intervention between active and standard of care. The hypothesis is that those on Lovaza will have less progression of coronary plaque compared to those in usual care.

    Measured: Baseline and 30 months

Secondary outcomes (10)
  1. Coronary artery plaque assessment

    1. Percent atheroma volume calculated as the proportion of the entire vessel wall occupied by atherosclerotic plaque and total atheroma volume, normalized to segment length.
    2. Maximum percent diameter stenosis and minimal luminal diameter.
    3. Number of subjects with categorical variables of maximal stenosis >50% and number with 3-vessel disease >20%.
    4. Number of subjects with stenosis of 0-29%, 30-49%, 50-69% and >70% stenosis at baseline compared to 30 months.
    5. Change in remodeling index - ratio of plaque volume at the most diseased site compared to the least diseased site.

    Measured: Baseline and 30 months

  2. Effect of Lovaza on Physical Function, Pain, Stiffness and Exercise

    Those on Lovaza will have better physical function and less pain and stiffness as assessed by the WOMAC questionnaire and more minutes of exercise per week compared to control

    Measured: Baseline and 1 year

  3. Inflammatory markers

    Compared to usual care, those on Lovaza will have reduction of mediators of inflammation in the circulation, including CRP, PAI-1, serum amyloid A, MMP-9 and fibrinogen, pro-inflammatory cytokines including IL-6, TNF-a and IL-1b, the adhesion molecules VCAM-1 and ICAM-1, increase in adiponectin and reduction in serum nitrotyrosine as a marker of oxidative stress. Additional inflammatory markers may be identified in the future and measured.

    Measured: Baseline and 30 months

  4. Pericardial Fat

    The amount of pericardial fat will be quantitated by CT at baseline and 30-month follow-up. The percent change between the two time-frames will be measured. Those on Lovaza and/or those who have lost weight will have a reduction (or lack of increase) in pericardial fat at 30-months compared to those in usual care.

    Measured: Baseline and 30 months

  5. Insulin Resistance

    Insulin resistance will be assessed by fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) at baseline and 30-months in the two study groups.

    Measured: Baseline and 30 months

  6. Nonalcoholic steatohepatitis (NASH)

    Reduction of inflammation in the liver associated with nonalcoholic steatohepatitis (NASH), a component of the metabolic syndrome, and reduction of fatty liver quantitated by computerized tomography and levels of AST and ALT as markers of liver inflammation related to NASH.

    Measured: Baseline and 30 months

  7. Vitamin D Levels and coronary plaque progression

    1. Investigation of the relationship between vitamin D status and coronary plaque progression, insulin resistance (HOMA-IR), beta-cell function (HOMA-%beta) and inflammatory cytokines
    2. Do baseline vitamin D levels predict response to omega-3 fatty acid supplementation?

    Measured: Baseline and 30 months

  8. Cognitive function

    To determine if those on Lovaza have less decline in cognitive function at 1 year and 30 months of follow-up compared to those in the usual care group.

    Measured: Baseline, 1 year and 30-months

  9. Exercise capacity and coronary plaque

    To determine if exercise capacity correlates with coronary plaque measurements. The hypothesis is that those with better exercise capacity will have lower amounts of coronary plaque.

    Measured: Baseline

  10. Urinary microalbumin and coronary plaque

    At baseline, subjects with lower urinary microalbumin will have lower amounts of coronary plaque. Those taking Lovaza will have less increase in urinary microalbmumin at 30-month follow-up compared to those in usual care.

    Measured: Baseline and 30-months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jun 2012 (estimated)
  2. Study startJun 2009
  3. Primary completion15 Jan 2015
  4. Study completion15 Jan 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
338 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01624727
Sponsor's protocol ID
2006P000175
Other IDs
P50HL083813
Acronym
HEARTS
Status last verified
Sep 2017
First submitted
15 May 2012
Last updated
27 Sep 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Ahmad B, Daher R, Malik A, Jeong YN, Welty FK. Omega-3 fatty acids and oral and systemic inflammation: A secondary analysis of a randomized trial in patients with coronary artery disease. J Am Dent Assoc. 2026 Aug;157(8):819-827. doi: 10.1016/j.adaj.2025.12.013. Epub 2026 Feb 5.

    PubMed 41642164
  • Welty FK, Hariri E, Asbeutah AA, Daher R, Amangurbanova M, Chedid G, Elajami TK, Alfaddagh A, Malik A. Regression of Coronary Fatty Plaque and Risk of Cardiac Events According to Blood Pressure Status: Data From a Randomized Trial of Eicosapentaenoic Acid and Docosahexaenoic Acid in Patients With Coronary Artery Disease. J Am Heart Assoc. 2023 Sep 19;12(18):e030071. doi: 10.1161/JAHA.123.030071. Epub 2023 Sep 8.

    PubMed 37681568
  • Chedid G, Malik A, Daher R, Welty FK. Higher exercise capacity, but not omega-3 fatty acid consumption, predicts lower coronary artery calcium scores in women and men with coronary artery disease. Atherosclerosis. 2023 Nov;384:117168. doi: 10.1016/j.atherosclerosis.2023.06.074. Epub 2023 Jun 26.

    PubMed 37541921
  • Welty FK, Schulte F, Alfaddagh A, Elajami TK, Bistrian BR, Hardt M. Regression of human coronary artery plaque is associated with a high ratio of (18-hydroxy-eicosapentaenoic acid + resolvin E1) to leukotriene B4. FASEB J. 2021 Apr;35(4):e21448. doi: 10.1096/fj.202002471R.

    PubMed 33749913
  • Malik A, Ramadan A, Vemuri B, Siddiq W, Amangurbanova M, Ali A, Welty FK. omega-3 Ethyl ester results in better cognitive function at 12 and 30 months than control in cognitively healthy subjects with coronary artery disease: a secondary analysis of a randomized clinical trial. Am J Clin Nutr. 2021 May 8;113(5):1168-1176. doi: 10.1093/ajcn/nqaa420.

    PubMed 33675344
  • Malik A, Kanduri JS, Asbeutah AAA, Khraishah H, Shen C, Welty FK. Exercise Capacity, Coronary Artery Fatty Plaque, Coronary Calcium Score, and Cardiovascular Events in Subjects With Stable Coronary Artery Disease. J Am Heart Assoc. 2020 Apr 7;9(7):e014919. doi: 10.1161/JAHA.119.014919. Epub 2020 Mar 26.

    PubMed 32212910
  • Alfaddagh A, Elajami TK, Saleh M, Mohebali D, Bistrian BR, Welty FK. An omega-3 fatty acid plasma index >/=4% prevents progression of coronary artery plaque in patients with coronary artery disease on statin treatment. Atherosclerosis. 2019 Jun;285:153-162. doi: 10.1016/j.atherosclerosis.2019.04.213. Epub 2019 Apr 13.

    PubMed 31055222
  • Alfaddagh A, Elajami TK, Ashfaque H, Saleh M, Bistrian BR, Welty FK. Effect of Eicosapentaenoic and Docosahexaenoic Acids Added to Statin Therapy on Coronary Artery Plaque in Patients With Coronary Artery Disease: A Randomized Clinical Trial. J Am Heart Assoc. 2017 Dec 15;6(12):e006981. doi: 10.1161/JAHA.117.006981.

    PubMed 29246960
  • Elajami TK, Alfaddagh A, Lakshminarayan D, Soliman M, Chandnani M, Welty FK. Eicosapentaenoic and Docosahexaenoic Acids Attenuate Progression of Albuminuria in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease. J Am Heart Assoc. 2017 Jul 14;6(7):e004740. doi: 10.1161/JAHA.116.004740.

    PubMed 28710178

Questions about this trial

What is this clinical trial studying?

A study testing Omega 3 acid ethyl esters in people with Coronary Heart Disease and Metabolic Syndrome, run by Beth Israel Deaconess Medical Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The primary endpoint is change in coronary noncalcified plaque volume. (time frame: Baseline and 30 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01624727, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2017.

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