Slowing HEART diSease With Lifestyle and Omega-3 Fatty Acids (HEARTS)
Slowing HEART diSease With Lifestyle and Omega-3 Fatty Acids (HEARTS)
調査の概要
詳細な説明
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:
- Change in total plaque volume per patient.
- improvement in physical function and exercise and reduction in pain and stiffness as measured by the WOMAC questionnaire
- 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.
- Reduction of insulin resistance assessed by fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR).
- 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.
- 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.
- 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.
研究の種類
入学 (実際)
段階
- 適用できない
連絡先と場所
研究場所
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Massachusetts
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Boston、Massachusetts、アメリカ、02215
- Beth Israel Deaconess Medical Center
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Milton、Massachusetts、アメリカ、02186
- South Shore Medical Group
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- 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
- 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
Exclusion criteria
- 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
- 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)
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研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
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介入なし: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.
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アクティブコンパレータ:Lovaza (Omega 3 ethyl esters)
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Lovaza 3.6 g daily
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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The primary endpoint is change in coronary noncalcified plaque volume.
時間枠:Baseline and 30 months
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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.
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Baseline and 30 months
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Coronary artery plaque assessment
時間枠:Baseline and 30 months
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Baseline and 30 months
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Effect of Lovaza on Physical Function, Pain, Stiffness and Exercise
時間枠:Baseline and 1 year
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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
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Baseline and 1 year
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Inflammatory markers
時間枠:Baseline and 30 months
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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.
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Baseline and 30 months
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Pericardial Fat
時間枠:Baseline and 30 months
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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.
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Baseline and 30 months
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Insulin Resistance
時間枠:Baseline and 30 months
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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.
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Baseline and 30 months
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Nonalcoholic steatohepatitis (NASH)
時間枠:Baseline and 30 months
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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.
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Baseline and 30 months
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Vitamin D Levels and coronary plaque progression
時間枠:Baseline and 30 months
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Baseline and 30 months
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Cognitive function
時間枠:Baseline, 1 year and 30-months
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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.
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Baseline, 1 year and 30-months
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Exercise capacity and coronary plaque
時間枠:Baseline
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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.
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Baseline
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Urinary microalbumin and coronary plaque
時間枠:Baseline and 30-months
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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.
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Baseline and 30-months
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協力者と研究者
捜査官
- 主任研究者:Francine K Welty, MD, PhD、Beth Israel Deaconess Medical Center
出版物と役立つリンク
一般刊行物
- 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 B(4). FASEB J. 2021 Apr;35(4):e21448. doi: 10.1096/fj.202002471R.
- 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.
- 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.
- 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.
- 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.
- 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.
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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