Conjugated Linoleic Acid and Atherosclerosis
Condition: Atherosclerosis
MeSH terms: Atherosclerosis
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): oil rich in cis9, trans11 conjugated linoleic acid; placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 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.; identical placebo capsules.
Other intervention name(s): oil rich in cis9, trans11 CLA; no other names
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: atherosclerosis; dietary supplements; randomised controlled trial; arterial stiffness; linoleic acid