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Conjugated Linoleic Acid and Atherosclerosis

U

UMC Utrecht

Status and phase

Completed
Phase 3

Conditions

Atherosclerosis

Treatments

Dietary Supplement: oil rich in cis9, trans11 conjugated linoleic acid
Dietary Supplement: placebo

Study type

Interventional

Funder types

Other

Identifiers

Details and patient eligibility

About

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.

Full 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.

Enrollment

401 patients

Sex

All

Ages

40 to 70 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

  • Written and signed informed consent
  • Healthy men and women
  • Between 40-70 years of age
  • Body mass index > 25 kg/m2

Exclusion criteria

  • Inability to understand the patient information
  • Inability to speak, read and understand the Dutch language
  • Indication (BP over 160/90) or using blood pressure lowering drugs
  • Indication (total cholesterol > 8 mmol/l) or using lipid lowering drugs
  • Indication (glucose > 7 mmol/l) or using glucose lowering drugs
  • Alcohol abuse (>21 alcoholic beverages per week)
  • Women who are pregnant, lactating or who are planning to become pregnant
  • Symptomatic vascular disease
  • Use of fish oils (omega 3/6,capsules or oil)
  • Use of plant stanols/sterols (margarines like benecol, pro active)
  • Use of weight loss supplements
  • Receipt of any investigational treatment (drug or device) within 30 days prior to visit 1

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

401 participants in 2 patient groups, including a placebo group

placebo
Placebo Comparator group
Description:
The control oil is based on the general fat consumption in a Western population and consists of an equal amount (4 gr) of fat. It is a blend of palm (80%) and soybean oil (20%). Two capsules will be taken in the morning and two in the evening.
Treatment:
Dietary Supplement: placebo
Dietary Supplement: oil rich in cis9, trans11 conjugated linoleic acid
oil rich in cis9, trans11 CLA
Active Comparator group
Description:
Subjects 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.
Treatment:
Dietary Supplement: placebo
Dietary Supplement: oil rich in cis9, trans11 conjugated linoleic acid

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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