Slowing HEART diSease With Lifestyle and Omega-3 Fatty Acids

NCT ID: NCT01624727

Last Updated: 2017-09-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

338 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-06-30

Study Completion Date

2015-01-15

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Coronary Heart Disease Metabolic Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Usual care

Those 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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Lovaza (Omega 3 ethyl esters)

Group Type ACTIVE_COMPARATOR

Omega 3 acid ethyl esters

Intervention Type DIETARY_SUPPLEMENT

Lovaza 3.6 g daily

Interventions

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Omega 3 acid ethyl esters

Lovaza 3.6 g daily

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

1. coronary artery disease
2. previous myocardial infarction
3. angioplasty (\> 6 months ago)
4. previous coronary bypass surgery (\> 12 months ago)
5. stable angina
6. non-calcified plaque on prior CT
7. abnormal exercise tolerance test
8. aged 21- 80 years
9. 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)
10. stable dose of statin for 1 month at screening or unable to tolerate a statin
11. 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
12. ALT, AST) \< 3 times upper limits of normal)
13. normal thyroid function or on stable dose replacement therapy
14. an ETT performed within 12 months prior

Exclusion Criteria

1. unstable angina (increase in frequency or severity of anginal episodes or development of chest pain at rest)
2. significant obstructive disease in left main coronary artery, ostial LAD or newly diagnosed three-vessel disease since prior cardiac catheterization by MDCTA
3. significant heart failure (NYHA class III and IV)
4. Current atrial fibrillation or Wolf-Parkinson-White (WPW) syndrome
5. allergy to beta-blocker in subjects with resting heart rate \> 65 bpm
6. systolic blood pressure \> 160 mm Hg
7. diastolic BP \> 100 mm Hg
8. persons with allergies to iodinated contrast material or shellfish
9. allergy to nitroglycerin
10. history of asthma only if unable to tolerate beta-blockers
11. BMI \> 35 kg/m2 if female and \> 40 kg/m2 if male
12. body weight \> 350 lbs
13. Use of drugs for weight loss \[eg Xenical (orlistat), Meridia (sibutramine), Acutrim (phenylpropanolamine) or similar over-the-counter medications\] within three months of screening
14. surgery within 30 days of screening
15. history of acquired immune deficiency syndrome or human immunodeficiency virus (HIV)
16. 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
17. medicine for erectile dysfunction within 72 hours prior to MDCTA
18. Prior stroke with residual cognitive deficit or functional deficit preventing any type of exercise
19. Current chemotherapy or radiation for malignancy
20. 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:

1. Transient cavity dilation
2. More than one vascular territory involved with reversible defect (multiple defects)
3. 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)

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Minimum Eligible Age

21 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Tufts Medical Center

OTHER

Sponsor Role collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Francine K. Welty

Associate Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Francine K Welty, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

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Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

South Shore Medical Group

Milton, Massachusetts, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 37681568 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37541921 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33749913 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33675344 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32212910 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31055222 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29246960 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28710178 (View on PubMed)

Other Identifiers

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P50HL083813

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2006P000175

Identifier Type: -

Identifier Source: org_study_id