Trial record 19 of 213 for:    heart disease AND women OR coronary microvascular disease OR cardiac syndrome X | Open Studies | NIH, U.S. Fed

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2012 by Beth Israel Deaconess Medical Center
Sponsor:
Collaborators:
Tufts Medical Center
Information provided by (Responsible Party):
Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT01624727
First received: May 15, 2012
Last updated: June 19, 2012
Last verified: June 2012
  Purpose

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


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • The primary endpoint is change in coronary noncalcified plaque volume. [ Time Frame: Baseline and 30 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.

  • Metabolic syndrome parameters [ Time Frame: Baseline and 30 months ] [ Designated as safety issue: No ]
    Those on Lovaza will have improvement in parameters of the metabolic syndrome assessed by measures of systolic and diastolic blood pressure, lipid profiles (total cholesterol, triglycerides, HDL and LDL) and abdominal adiposity (quantitated by computerized tomography) and waist/hip ratio compared to those in usual care.

  • Inflammatory markers [ Time Frame: Baseline and 30 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.

  • Improvement in Medications [ Time Frame: Baseline and 30 months ] [ Designated as safety issue: No ]
    Comparison of rates of addition of anti-hypertensive, diabetic, or lipid lowering medications will be made between the two study arms at baseline and 30-months of follow-up.

  • New onset diabetes [ Time Frame: Baseline and 30 months ] [ Designated as safety issue: No ]
    Comparison will be made of the numbers of persons who progress to diabetes between the two study groups at 30-months of follow-up.

  • Change in Metabolic Syndrome [ Time Frame: Baseline and 30 months ] [ Designated as safety issue: No ]
    Comparison of numbers of persons who regress from ATPIII metabolic syndrome criteria (for those with metabolic syndrome) will be made between baseline and 30-month follow-up in the two study groups.

  • Vitamin D and coronary plaque [ Time Frame: Baseline and 30 months ] [ Designated as safety issue: No ]
    Investigation of the relationship between vitamin D status and coronary plaque (both non-calcified and calcified), as well as with insulin resistance (HOMA-IR), beta-cell function (HOMA-%beta), and serum levels of inflammatory cytokines and adhesion molecules, known to be related to CVD risk will be made at baseline and 30-months in the two study groups.

  • Vitamin D levels and plaque progression [ Time Frame: Baseline and 30 months ] [ Designated as safety issue: No ]
    Determination of whether baseline vitamin D levels predicts clinical response to omega-3 fatty acid supplementation and whether hypovitaminosis D is associated with plaque progression.

  • Cognitive function [ Time Frame: Baseline, 1 year and 30-months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.

  • Visceral Fat [ Time Frame: Baseline and 30-months ] [ Designated as safety issue: No ]
    Those who lose weight will have a decrease in the amount of visceral fat (as measured by CT) and improvement in waist-hip ratio compared to those in usual care.


Estimated Enrollment: 338
Study Start Date: June 2009
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: November 2014 (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
Other Name: Omega 3 acid ethyl esters

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 intensive lifestyle intervention (exercise and nutrition counselling geared toward weight loss with 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 active lifestyle 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 lifestyle will be associated with:

  1. Change in total plaque volume per patient.
  2. Improvement in the metabolic syndrome assessed by measures of waist/hip ratio, systolic and diastolic blood pressure, lipid profiles (total cholesterol, triglycerides, HDL and LDL), and abdominal adiposity quantitated by computerized tomography.
  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. Comparison of rates of addition of anti-hypertensive, diabetic, or lipid lowering medication.
  7. Comparison of numbers of persons with metabolic syndrome who progress to diabetes between groups.
  8. Comparison of numbers of persons who regress from ATPIII metabolic syndrome criteria.
  9. Investigation of the relationship between vitamin D status and coronary calcification, as well as with insulin resistance (HOMA-IR), beta-cell function (HOMA-%beta), and serum levels of inflammatory cytokines and adhesion molecules, known to be related to CVD risk.
  10. Determination of whether baseline vitamin D levels predict clinical response to the lifestyle intervention, and whether hypovitaminosis D is associated with plaque progression.
  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
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)

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  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01624727

Contacts
Contact: Francine K Welty, MD, PhD 617-632-7659 fwelty@bidmc.harvard.edu

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Sub-Investigator: Melvin Clouse, MD         
Sub-Investigator: Thomas Hauser, MD, MPH         
South Shore Medical Group Recruiting
Milton, Massachusetts, United States, 02186
Contact: Jon Cronin, MD         
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Tufts Medical Center
Investigators
Principal Investigator: Francine K Welty, MD, PhD Beth Israel Deaconess Medical Center
  More Information

No publications provided

Responsible Party: Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01624727     History of Changes
Other Study ID Numbers: 2006P-000175, P50HL083813
Study First Received: May 15, 2012
Last Updated: June 19, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Beth Israel Deaconess Medical Center:
Coronary heart disease
metabolic syndrome
CT angiography

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

ClinicalTrials.gov processed this record on July 22, 2014