- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT01624727
Slowing HEART diSease With Lifestyle and Omega-3 Fatty Acids (HEARTS)
Slowing HEART diSease With Lifestyle and Omega-3 Fatty Acids (HEARTS)
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Unzutreffend
Kontakte und Standorte
Studienorte
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Massachusetts
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Boston, Massachusetts, Vereinigte Staaten, 02215
- Beth Israel Deaconess Medical Center
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Milton, Massachusetts, Vereinigte Staaten, 02186
- South Shore Medical Group
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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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Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Kein Eingriff: 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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Aktiver Komparator: Lovaza (Omega 3 ethyl esters)
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Lovaza 3.6 g daily
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
The primary endpoint is change in coronary noncalcified plaque volume.
Zeitfenster: 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.
|
Baseline and 30 months
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Coronary artery plaque assessment
Zeitfenster: Baseline and 30 months
|
|
Baseline and 30 months
|
Effect of Lovaza on Physical Function, Pain, Stiffness and Exercise
Zeitfenster: 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
|
Baseline and 1 year
|
Inflammatory markers
Zeitfenster: 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.
|
Baseline and 30 months
|
Pericardial Fat
Zeitfenster: 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.
|
Baseline and 30 months
|
Insulin Resistance
Zeitfenster: 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.
|
Baseline and 30 months
|
Nonalcoholic steatohepatitis (NASH)
Zeitfenster: 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.
|
Baseline and 30 months
|
Vitamin D Levels and coronary plaque progression
Zeitfenster: Baseline and 30 months
|
|
Baseline and 30 months
|
Cognitive function
Zeitfenster: 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
|
Exercise capacity and coronary plaque
Zeitfenster: 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.
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Baseline
|
Urinary microalbumin and coronary plaque
Zeitfenster: 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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Mitarbeiter und Ermittler
Ermittler
- Hauptermittler: Francine K Welty, MD, PhD, Beth Israel Deaconess Medical Center
Publikationen und hilfreiche Links
Allgemeine Veröffentlichungen
- 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.
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- 2006P000175
- P50HL083813 (NIH)
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