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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01624727
First Posted: June 21, 2012
Last Update Posted: September 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Tufts Medical Center
Information provided by (Responsible Party):
Francine K. Welty, Beth Israel Deaconess Medical Center
  Purpose
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.

Condition Intervention
Coronary Heart Disease Metabolic Syndrome Dietary Supplement: Omega 3 acid ethyl esters

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Slowing HEART diSease With Lifestyle and Omega-3 Fatty Acids (HEARTS)

Resource links provided by NLM:


Further study details as provided by Francine K. Welty, Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • The primary endpoint is change in coronary noncalcified plaque volume. [ Time Frame: Baseline and 30 months ]
    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.


Secondary Outcome Measures:
  • Coronary artery plaque assessment [ Time Frame: Baseline and 30 months ]
    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.

  • Effect of Lovaza on Physical Function, Pain, Stiffness and Exercise [ Time Frame: Baseline and 1 year ]
    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

  • Inflammatory markers [ Time Frame: Baseline and 30 months ]
    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.

  • Pericardial Fat [ Time Frame: Baseline and 30 months ]
    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.

  • Insulin Resistance [ Time Frame: Baseline and 30 months ]
    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.

  • Nonalcoholic steatohepatitis (NASH) [ Time Frame: Baseline and 30 months ]
    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.

  • Vitamin D Levels and coronary plaque progression [ Time Frame: Baseline and 30 months ]
    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?

  • Cognitive function [ Time Frame: Baseline, 1 year and 30-months ]
    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.

  • Exercise capacity and coronary plaque [ Time Frame: Baseline ]
    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.

  • Urinary microalbumin and coronary plaque [ Time Frame: Baseline and 30-months ]
    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.


Enrollment: 338
Study Start Date: June 2009
Study Completion Date: January 15, 2015
Primary Completion Date: January 15, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 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.
Active Comparator: Lovaza (Omega 3 ethyl esters) Dietary Supplement: Omega 3 acid ethyl esters
Lovaza 3.6 g daily

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.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01624727


Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
South Shore Medical Group
Milton, Massachusetts, United States, 02186
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
National Heart, Lung, and Blood Institute (NHLBI)
Tufts Medical Center
Investigators
Principal Investigator: Francine K Welty, MD, PhD Beth Israel Deaconess Medical Center
  More Information

Responsible Party: Francine K. Welty, Associate Professor of Medicine, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01624727     History of Changes
Other Study ID Numbers: 2006P000175
P50HL083813 ( U.S. NIH Grant/Contract )
First Submitted: May 15, 2012
First Posted: June 21, 2012
Last Update Posted: September 27, 2017
Last Verified: September 2017

Keywords provided by Francine K. Welty, Beth Israel Deaconess Medical Center:
Coronary heart disease
metabolic syndrome
CT angiography

Additional relevant MeSH terms:
Heart Diseases
Metabolic Syndrome X
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
Cardiovascular Diseases
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases