Heart & Health Study

Heart Disease Clinical Trial

Official title:

Variation in the ALOX5 Gene and Response to Omega-3 Fatty Acid Supplements

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00536185
• Other study ID #: R21AT003411-01A1
• Secondary ID: R21AT003411-01A1
• Status: Completed
• Phase: N/A
• First received: September 5, 2007
• Last updated: August 3, 2011
• Start date: December 2006
• Est. completion date: July 2008

Study information

• Verified date: August 2011
• Source: USDA, Western Human Nutrition Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

We hope to learn more about why certain people have higher levels of the 5-LO protein and whether taking fish oil supplements gives such individuals greater protection than others against cardiovascular disease. The 5-LO protein is important in the development of heart disease because it converts a type of oil from meat into a compound that can cause inflammation in blood vessels. This inflammation is a major cause of heart disease.

Researchers think that people with higher levels of a protein called 5-LO in their white blood cells may have a healthier response to using fish oil supplements than do people with lower levels of this protein.

Description:

Fish oil supplements will be given to subjects with different variants in the promoter region of the arachidonate 5-lipoxygenase (ALOX5) gene and outcome measures will be evaluated after 6 wk of supplementation. These outcomes include ALOX5 protein levels (also called 5-lipoxygenase, or 5-LO), leukotriene levels, markers of inflammation, and blood lipids. The 5-LO enzyme converts arachidonic acid (AA) to leukotrienes that promote inflammation. Subjects with different promoter variants are hypothesized to have different basal or stimulated levels of 5-LO expression. Preliminary data suggests that subjects with a promoter variant that causes increased 5-LO expression also may have a "better" anti-inflammatory or lipid-lowering response to fish oil supplements. The homozygous variant genotype is much more common in African Americans than other groups thus we propose to conduct the study in African Americans. The fish oil eicosapentaenoic acid (EPA) competitively inhibits conversion of AA to pro-inflammatory 4-series leukotrienes.

The grant proposes to conduct a community-based, double-masked, randomized, placebo-controlled trial; n = 15/group, total = 166 (genotypes 44 will have n = 8). The intervention group will receive 5.0 g/d fish oil concentrate (3.0 g/d EPA + DHA) for 6 wk. The study will be conducted in Oakland, Davis, and Sacramento, California where African Americans 20 - 59 y of age without serious chronic disease will be recruited.

A recent observational study indicates that subjects with a variant allele for ALOX5 may be at greater risk for cardiovascular disease and, at the same time, may derive a greater benefit from omega-3 fatty acid supplements than do subjects homozygous for the common allele. The variant alleles are less common in the white population (18%) than in the black population (52%). Since African Americans have a higher prevalence of cardiovascular disease and of the ALOX5 variant alleles, as shown in epidemiologic studies, they may have a greater benefit from omega-3 supplementation in the reduction of inflammation and cardiovascular risk factors. Recruitment will be conducted through the community service, Ethnic Health Institute (EHI), of Alta Bates Summit Medical Center in conjunction with UCD, and outreach efforts from the USDA, ARS, Western Human Nutrition Research Center (WHNRC) at UC Davis. We will determine if subjects with one or two variant ALOX5 alleles have higher ALOX5 gene expression, higher production of AA-derived leukotrienes, and a better response to omega-3 supplements than do subjects homozygous for the common allele.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 166
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 59 Years

Eligibility

Inclusion Criteria:

• African-American, Black, or persons of African Descent

• Generally Healthy

• 20 - 59 years of age

Exclusion Criteria:

• Chronic Diseases (Heart disease, cancer, diabetes, etc.)

• Smoke > 14 cigarettes per week

• Consume > 14 alcoholic drinks per week

• Pregnant Women

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Heart Disease
• Heart Diseases

Intervention

Dietary Supplement:
• Fish Oil
capsules, 5.0 g/d fish oil concentrate (3.0 g/d EPA + DHA), 6 weeks
• Placebo
capsule, 5.0 g/d corn/soybean oil (50/50 mixture), 6 weeks

Locations

Country	Name	City	State
United States	UC Davis, Western Human Nutrition Research Center	Davis	California
United States	Ethnich Health Institute	Oakland	California
United States	UC Davis (TICON-1)	Sacramento	California

Sponsors (7)

Lead Sponsor	Collaborator
USDA, Western Human Nutrition Research Center	Alta Bates Summit Medical Center, National Center for Complementary and Integrative Health (NCCIH), Office of Dietary Supplements (ODS), United States Department of Agriculture (USDA), University of California, Davis, University of Southern California

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	(a) ALOX5 mRNA and protein in resting and stimulated cultures of purified monocytes and purified granulocytes (b) Arachidonic acid-derived leukotrienes in resting and stimulated cultures of whole blood, purified monocytes and purified granulocytes		6 weeks	No
Secondary	Proinflammatory cytokines, C-reactive protein, triglycerides, glucose and insulin in plasma, and resting heart rate and blood pressure		6 weeks	Yes

External Links

•   Western Human Nutrition Research website