NCT00706745

Conjugated Linoleic Acid and Atherosclerosis

Possible Effects of Supplementation With Cis-9, Trans-11 Conjugated Linoleic Acid on Markers of Atherosclerosis

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 401 (actual)
• Sponsor: UMC Utrecht · Academic / Other
• Sex: All
• Age: 40 Years – 70 Years
• Healthy volunteers: Accepted

Summary

Rationale: Cis-9, trans-11 conjugated linoleic acid (CLA) can protect against the atherosclerosis development in several animal models. Studies in transgenic mice have shown that mechanisms might involve beneficial effects on lipoprotein metabolism and insulin sensitivity and in addition activation of anti-inflammatory pathways. A very limited amount of human studies have not shown similar beneficial effect of cis9,trans11-CLA on insulin sensitivity in obese subjects, yet cis9,trans11-CLA did improve the lipoprotein profile in healthy subjects. The effect of cis9,trans11-CLA supplementation on alternative early biomarkers of atherosclerosis, like aortic pulse wave velocity, and alternative biomarkers identified through platelet proteomics, has not been assessed before, and may add valuable insights into the mechanism of this functional fatty acid in humans. Objective: To assess the effect of increased intake of cis9 trans11-CLA on development of atherosclerosis, as assessed with aortic pulse wave velocity and on alternative biomarkers. Study design: The study is designed as a double blind randomised placebo controlled parallel group trial. Study population: 400 men and women, between 40 and 70 years of age, with a body mass index of 25 kg/m2 or above. Subjects with previous symptomatic vascular disease or diabetes mellitus and subjects on blood pressure lowering or lipid lowering medication are excluded. Intervention: Subjects in the intervention arm will receive daily 4 g of CLA oil (2.6 g cis9,trans11-CLA), 2 capsules to be taken in the morning and 2 in the evening. The subjects in the control arm receive 4 identical placebo capsules. Main study parameters/endpoints: The main study outcome is difference between treatment arms in change in aortic pulse wave velocity after 6 months intervention.

Detailed description

Rationale: Cis-9, trans-11 conjugated linoleic acid (CLA) can protect against the atherosclerosis development in several animal models. Studies in transgenic mice have shown that mechanisms might involve beneficial effects on lipoprotein metabolism and insulin sensitivity and in addition activation of anti-inflammatory pathways. A very limited amount of human studies have not shown similar beneficial effect of cis9,trans11-CLA on insulin sensitivity in obese subjects, yet cis9,trans11-CLA did improve the lipoprotein profile in healthy subjects. The effect of cis9,trans11-CLA supplementation on alternative early biomarkers of atherosclerosis, like aortic pulse wave velocity, and alternative biomarkers identified through platelet proteomics, has not been assessed before, and may add valuable insights into the mechanism of this functional fatty acid in humans. Objective: To assess the effect of increased intake of cis9 trans11-CLA on development of atherosclerosis, as assessed with aortic pulse wave velocity and on alternative biomarkers. Study design: The study is designed as a double blind randomised placebo controlled parallel group trial. Study population: The study population comprises 400 men and women, between 40 and 70 years of age, with a body mass index of 25 kg/m2 or above. Subjects with previous symptomatic vascular disease or diabetes mellitus and subjects on blood pressure lowering or lipid lowering medication are excluded. Intervention: Subjects in the intervention arm will receive daily 4 g of CLA oil (2.6 g cis9,trans11-CLA), 2 capsules to be taken in the morning and 2 in the evening. The subjects in the control arm receive 4 identical placebo capsules. Main study parameters/endpoints: The main study outcome is difference between treatment arms in change in aortic pulse wave velocity after 6 months intervention. Secondary outcomes are differences between treatment groups in change in serum lipids (total, LDL- and HDL cholesterol and triglycerides) and change in systolic and diastolic blood pressure, as well as in F2-isoprostanes and platelet biomarkers of haemostatic function (proteomics). Blood samples will be stored for assessment of plasma parameters of glucose intolerance, inflammation and endothelial function. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The assessment of aortic pulse wave velocity is non-invasive and does not carry any risks nor has any side effects. The assessment of lipids and blood pressure might sometimes carry some discomfort but can be seen as routine procedures. Completion of questionnaire needs to done once. The participants need to come to the research center three times. Based on findings of several short-term and long-term studies using the compound, no excess serious adverse events were found.

Conditions

• Atherosclerosis

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	oil rich in cis9, trans11 conjugated linoleic acid	An oil rich in cis9, trans11 conjugated linoleic acid (cis9,trans11-CLA). Of the total amount of CLA in the oil, 80% is cis9, trans11-CLA and 20% trans10, cis12-CLA. In total 4 grams of oil will be given daily. The oil will be taken in the form of soft gel capsules. Two capsules will be taken in the morning and two in the evening.
DIETARY_SUPPLEMENT	placebo	identical placebo capsules.

Timeline

• Start date: 2007-06-01
• Primary completion: 2008-11-01
• Completion: 2008-12-01
• First posted: 2008-06-30
• Last updated: 2015-06-15

Locations

1 site across 1 country: Netherlands