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

• Sponsor: Denver Health and Hospital Authority (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00935766
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), GlaxoSmithKline (Industry)
• Enrollment: 76
• Location: 1
• Arms: 2
• Duration (Months): 30
• Patients Per Site Per Month: 2.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metabolic Diseases; Endocrine System Diseases; Heart Disease; Vascular Diseases; Diabetes; Cardiovascular Disease; Glucose Metabolism Disorders; Hypertension	Drug: Omega-3; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 76 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Latinos Using Cardio Health Actions to Reduce Risk (LUCHAR): Effect of Omega-3 Fatty Acids on Vascular Function and Inflammation
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Sugar Pill 4 tabs of placebo dependent on randomization	Drug: Placebo; Other Names: Sugar pill
Active Comparator: Omega 3 omega-3-acid ethyl esters and instructed to take 4 1 mg capsules daily	Drug: Omega-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.; Other Names: Lovaza

Outcome Measures

Primary Outcome Measures

1. Change in Pulse Wave Velocity in Active vs. Placebo-treated Patients. [Baseline, 3 months]

   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. .

Secondary Outcome Measures

1. Change in Lipoprotein-associated Phospholipase A2 (LpPLA2) [baseline, 3 months]

2. Change in hsCRP [baseline, 3 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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 exclusion criteria for participation in Aim 4.3 include:

• Pregnancy or breast-feeding

• Known sensitivity or allergy to fish

• Known sensitivity or allergy to omega-3 fatty acid supplements

• Taking omega-3 fatty acid supplements in the last 2 weeks- may participate after 2 week washout

• Triglycerides > 500 mg/dL.

• Alanine aminotransferase (ALT) levels above 3x upper limit of normal

• Not a good candidate for participation based on the opinion of the investigators.

• Current therapy with a fibric acid derivative

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Denver Health and Hospital Authority	Denver	Colorado	United States	80204

Sponsors and Collaborators

• Denver Health and Hospital Authority
• National Heart, Lung, and Blood Institute (NHLBI)
• GlaxoSmithKline

Investigators

• Principal Investigator: Carlin S Long, MD, Denver Health Medical Center Chief of Cardiology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Carlin Long, Cardiologist, Denver Health and Hospital Authority
• ClinicalTrials.gov Identifier: NCT00935766
• Other Study ID Numbers: 08-0722 LUCHAR AIM 4
• First Posted: Jul 9, 2009
• Last Update Posted: Sep 29, 2014
• Last Verified: Sep 1, 2014

• Keywords provided by Carlin Long, Cardiologist, Denver Health and Hospital Authority: Latinos Using Cardio Health Actions to Reduce Risk; Omega three Fatty Acids; Vascular Function and Inflammation
• Additional relevant MeSH terms: Cardiovascular Diseases; Heart Diseases; Vascular Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Endocrine System Diseases

Study Results

Participant Flow

Pre-assignment Detail	The study was discontinued early due to lack of funding and slow enrollment

Arm/Group Title	Placebo	Omega 3
Arm/Group Description	Placebo (Four 1-gram capsules daily)	omega-3-acid ethyl esters (Four 1-gram capsules daily)
Period Title: Overall Study
STARTED	42	34
COMPLETED	35	27
NOT COMPLETED	7	7

Baseline Characteristics

Arm/Group Title	Placebo	Omega 3	Total
Arm/Group Description	Placebo (Four 1-gram capsules daily)	omega-3-acid ethyl esters (Four 1-gram capsules daily)	Total of all reporting groups
Overall Participants	35	27	62
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.2 (10.8)	62.3 (9.7)	61.1 (10.3)
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	29 82.9%	22 81.5%	51 82.3%
>=65 years	6 17.1%	5 18.5%	11 17.7%
Sex: Female, Male (Count of Participants)
Female	22 62.9%	18 66.7%	40 64.5%
Male	13 37.1%	9 33.3%	22 35.5%
Region of Enrollment (participants) [Number]
United States	35 100%	27 100%	62 100%

Outcome Measures

1. Secondary Outcome

Title	Change in Lipoprotein-associated Phospholipase A2 (LpPLA2)
Time Frame	baseline, 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omega 3
Arm/Group Description	Placebo (Four 1-gram capsules daily)	omega-3-acid ethyl esters (Four 1-gram capsules daily)
Measure Participants	35	27
Mean (Standard Deviation) [ng/mL]	-6.1 (31.7)	-18.1 (41.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omega 3
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Change in hsCRP
Time Frame	baseline, 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omega 3
Arm/Group Description	Placebo (Four 1-gram capsules daily)	omega-3-acid ethyl esters (Four 1-gram capsules daily)
Measure Participants	35	27
Mean (Standard Deviation) [mg/L]	0.9 (4.4)	-0.9 (3.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omega 3
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments
	Method	Mixed Models Analysis
	Comments

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omega 3
Arm/Group Description	Placebo (Four 1-gram capsules daily)	omega-3-acid ethyl esters (Four 1-gram capsules daily)
Measure Participants	35	27
Mean (Standard Deviation) [cm/sec]	-33 (306)	-97 (182)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omega 3
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Arm/Group Title	Placebo		Omega 3
Arm/Group Description	Placebo (Four 1-gram capsules daily)		omega-3-acid ethyl esters (Four 1-gram capsules daily)
All Cause Mortality
	Placebo		Omega 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Omega 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Omega 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/34 (0%)

Limitations/Caveats

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

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The PI shall furnish copies of any proposed publication or presentation to the Sponsor for review at least thirty (30) days in advance of the submission of such proposed publication or presentation to a journal, editor or other third party. The sponsor shall have thirty (30) days after receipt of said copies, to object to such proposed presentation or proposed publication.