Heart & Health Study
|ClinicalTrials.gov Identifier: NCT00536185|
Recruitment Status : Completed
First Posted : September 27, 2007
Last Update Posted : August 4, 2011
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.
|Condition or disease||Intervention/treatment|
|Heart Disease||Dietary Supplement: Fish Oil Dietary Supplement: Placebo|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||166 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||Variation in the ALOX5 Gene and Response to Omega-3 Fatty Acid Supplements|
|Study Start Date :||December 2006|
|Primary Completion Date :||July 2008|
|Study Completion Date :||July 2008|
Dietary Supplement: Fish Oil
capsules, 5.0 g/d fish oil concentrate (3.0 g/d EPA + DHA), 6 weeks
|Placebo Comparator: 2||
Dietary Supplement: Placebo
capsule, 5.0 g/d corn/soybean oil (50/50 mixture), 6 weeks
- (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 [ Time Frame: 6 weeks ]
- Proinflammatory cytokines, C-reactive protein, triglycerides, glucose and insulin in plasma, and resting heart rate and blood pressure [ Time Frame: 6 weeks ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00536185
|United States, California|
|UC Davis, Western Human Nutrition Research Center|
|Davis, California, United States, 95616|
|Ethnich Health Institute|
|Oakland, California, United States, 94609|
|UC Davis (TICON-1)|
|Sacramento, California, United States, 95820|
|Principal Investigator:||Charles B Stephensen, PhD||UC Davis & U.S. Department of Agriculture|