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Effect of Fish Oil (Omega-3 Fatty Acids) on Arteries

Latinos Using Cardio Health Actions to Reduce Risk (LUCHAR): Effect of Omega-3 Fatty Acids on Vascular Function and Inflammation

Status
Terminated
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00935766
Enrollment
76
Registered
2009-07-09
Start date
2009-09-30
Completion date
2012-03-31
Last updated
2014-09-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cardiovascular Disease, Diabetes, Endocrine System Diseases, Glucose Metabolism Disorders, Heart Disease, Hypertension, Metabolic Diseases, Vascular Diseases

Keywords

Latinos Using Cardio Health Actions to Reduce Risk, Omega three Fatty Acids, Vascular Function and Inflammation

Brief summary

The overall objective of LUCHAR Specific Aims 4.1 and 4.2 is to assess the additional contribution of cardiovascular disease (CVD) risk markers to traditional biomedical risk factors in the prediction of pre-clinical CVD. Specific Aim 4.3 will test the impact of omega-3 fatty acid supplementation on risk markers and pre-clinical markers of CVD in Hispanic patients. Specific Aim 4.3: Conduct a randomized, placebo-controlled trial of the effect of omega-3 fatty acid supplementation on vascular function as measured by brachial artery reactivity (BAR) and on circulating inflammatory markers. Hypotheses: 1. Daily omega-3 fatty acid supplementation will improve vascular function in subjects at high risk for CVD. 2. Daily omega-3 fatty acid supplementation will reduce inflammatory protein panel scores in subjects at high risk for CVD.

Detailed description

Omega-3 fatty acids reduce triglycerides (TG) in a manner similar to fibric acids by lowering hepatic TG release, reducing VLDL production, stimulating lipoprotein lipase and enhancing TG clearance. Although statins are widely utilized among DH patients, our overall population, even those with CHD, have fairly low levels of LDL-cholesterol (Krantz et al, 2004). This likely reflects our population that is predominantly Latino with a high incidence of metabolic syndrome. Among our patients, we often achieve LDL-c NCEP targets, yet secondary goals for non-HDL, HDL, and TG are rarely achieved. This is an unmet opportunity given the strong independent contribution of non-HDL (McQueen et al, 2008), HDL (D'Agostino et al, 2008) and TG (Nordestgaard et al, 2007, Tirosh et al, 2007) to CHD risk, which may be particularly important in Latino populations. The study drug (LOVAZA) improves the TC/HDL ratio which is the strongest predictor of CHD events based on the \ 30,000 patient Interheart study noted above. LOVAZA has no hepatic P450 effects and for that matter no meaningful clinical adverse effects, making it advantageous for use in a population with multiple co-morbidities who are at risk for drug-drug interactions and have difficulty with medication adherence. Given the high incidence of insulin resistance among DH's predominately Latino CHD population, and strong lipid (Harris et al, 1997; Davidson et al 2007) as well outcome data in CHD (GISSI investigators, 1999) this agent has potential clinical utility in our population. To date, improved outcomes in non-CHD populations have not been demonstrated prospectively with LOVAZA. Although recent data suggest promising effects on inflammatory makers such as LpPLA2, the impact of LOVAZA on pre-clinical markers of atherosclerosis such as BAR and CIMT have not been well characterized particularly among Latinos. Moreover, changes in inflammatory markers have been limited and more expansive evaluations are currently available. Against this background we assessed whether LOVAZA might improve atherosclerotic risk via improvement in flow mediated dilation of the brachial artery as well as through reduction in a comprehensive inflammatory marker panel.

Interventions

DRUGOmega-3

Subjects meeting eligibility criteria will be randomized to receive a supply of omega-3-acid ethyl esters or placebo, and instructed to take 4 capsules daily. A 3-month supply of study drug will be given following randomization and at 3, 6, and 9 months. Subjects will be asked to bring unused supplies to each quarterly visit for ascertainment of adherence.

DRUGPlacebo

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)
CollaboratorNIH
GlaxoSmithKline
CollaboratorINDUSTRY
Denver Health and Hospital Authority
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Diagnosis of HTN * Hispanic or Non-Hispanic White * Age \> 18 * One additional CVD risk factor * Age \> 55 for males or \>65 for females * DM * Dyslipidemia O TC \>220 or O LDL \>130 or O on statin therapy * Current smoker * Chronic kidney disease defined as GFR \<60 ml/min/1.72m2 * BMI \> 30 kg/m2 * Positive microalbuminuria -Able to sign consent form and willing to complete 12-month follow- up period.

Exclusion criteria

used for SA3/4 will also apply for Aim 4.3. These include factors rendering assessment of endothelial function unreliable, such as: * Clinically manifest CVD (including angina, myocardial infarction, surgical or percutaneous coronary revascularization, stroke, cerebrovascular revascularization, peripheral vascular disease, heart failure, or valvular heart disease * Electrocardiographic evidence of prior myocardial infarction * Known valvular heart disease of at least moderate severity * Known left ventricular systolic dysfunction (LVEF \< 0.50) * End-stage renal disease * History of inflammatory disease or vasculitis (including rheumatoid arthritis, systemic lupus erythematosis, Raynaud phenomenon, or other connective tissue disease/vasculitides) * Corticosteroid therapy * Active substance abuse * Projected life-expectancy \<12 months due to comorbid condition * Plans to move away from the Denver area within 12 months * Previous trauma or surgery of the brachial artery * Upper arm circumference exceeding 42 cm. Additional

Design outcomes

Primary

MeasureTime frameDescription
Change in Pulse Wave Velocity in Active vs. Placebo-treated Patients.Baseline, 3 monthsWe conducted a prospective, randomized; double-blinded study of omega-3 fatty acids among 60 Latino and White hypertensive patients at risk for CVD. Patients received either 4-g omega-3 fatty acids or matched placebo daily. The principal outcome measure was change in brachial-ankle PWV. .

Secondary

MeasureTime frame
Change in Lipoprotein-associated Phospholipase A2 (LpPLA2)baseline, 3 months
Change in hsCRPbaseline, 3 months

Countries

United States

Participant flow

Pre-assignment details

The study was discontinued early due to lack of funding and slow enrollment

Participants by arm

ArmCount
Placebo
Placebo (Four 1-gram capsules daily)
35
Omega 3
omega-3-acid ethyl esters (Four 1-gram capsules daily)
27
Total62

Baseline characteristics

CharacteristicPlaceboOmega 3Total
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
6 Participants5 Participants11 Participants
Age, Categorical
Between 18 and 65 years
29 Participants22 Participants51 Participants
Age, Continuous60.2 years
STANDARD_DEVIATION 10.8
62.3 years
STANDARD_DEVIATION 9.7
61.1 years
STANDARD_DEVIATION 10.3
Region of Enrollment
United States
35 participants27 participants62 participants
Sex: Female, Male
Female
22 Participants18 Participants40 Participants
Sex: Female, Male
Male
13 Participants9 Participants22 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 420 / 34
serious
Total, serious adverse events
0 / 420 / 34

Outcome results

Primary

Change in Pulse Wave Velocity in Active vs. Placebo-treated Patients.

We conducted a prospective, randomized; double-blinded study of omega-3 fatty acids among 60 Latino and White hypertensive patients at risk for CVD. Patients received either 4-g omega-3 fatty acids or matched placebo daily. The principal outcome measure was change in brachial-ankle PWV. .

Time frame: Baseline, 3 months

ArmMeasureValue (MEAN)Dispersion
PlaceboChange in Pulse Wave Velocity in Active vs. Placebo-treated Patients.-33 cm/secStandard Deviation 306
Omega 3Change in Pulse Wave Velocity in Active vs. Placebo-treated Patients.-97 cm/secStandard Deviation 182
p-value: 0.36Mixed Models Analysis
Secondary

Change in hsCRP

Time frame: baseline, 3 months

ArmMeasureValue (MEAN)Dispersion
PlaceboChange in hsCRP0.9 mg/LStandard Deviation 4.4
Omega 3Change in hsCRP-0.9 mg/LStandard Deviation 3.1
p-value: 0.08Mixed Models Analysis
Secondary

Change in Lipoprotein-associated Phospholipase A2 (LpPLA2)

Time frame: baseline, 3 months

ArmMeasureValue (MEAN)Dispersion
PlaceboChange in Lipoprotein-associated Phospholipase A2 (LpPLA2)-6.1 ng/mLStandard Deviation 31.7
Omega 3Change in Lipoprotein-associated Phospholipase A2 (LpPLA2)-18.1 ng/mLStandard Deviation 41.1
p-value: 0.21Mixed Models Analysis

Source: ClinicalTrials.gov · Data processed: Mar 14, 2026