Conjugated Linoleic Acid and Atherosclerosis

Atherosclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00706745
• Other study ID #: CLA362
• Status: Completed
• Phase: Phase 3
• First received: June 26, 2008
• Last updated: June 11, 2015
• Start date: June 2007
• Est. completion date: December 2008

Study information

• Verified date: June 2015
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 401
• Est. completion date: December 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 40 Years to 70 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Atherosclerosis

Intervention

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.
• placebo
identical placebo capsules.

Locations

Country	Name	City	State
Netherlands	Julius Center for Health Sciences and Primary Care, UMC Utrecht	Utrecht

Sponsors (4)

Lead Sponsor	Collaborator
UMC Utrecht	Center Novem, Lipid Nutrition B.V, University of Aberdeen

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

Bachmair EM, Bots ML, Mennen LI, Kelder T, Evelo CT, Horgan GW, Ford I, de Roos B. Effect of supplementation with an 80:20 cis9,trans11 conjugated linoleic acid blend on the human platelet proteome. Mol Nutr Food Res. 2012 Jul;56(7):1148-59. doi: 10.1002/ — View Citation

Sluijs I, Plantinga Y, de Roos B, Mennen LI, Bots ML. Dietary supplementation with cis-9,trans-11 conjugated linoleic acid and aortic stiffness in overweight and obese adults. Am J Clin Nutr. 2010 Jan;91(1):175-83. doi: 10.3945/ajcn.2009.28192. Epub 2009 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The main study outcome is difference between treatment arms in change in aortic pulse wave velocity after 6 months intervention.		6 months	No
Secondary	change in serum lipids (total, LDL- and HDL cholesterol and triglycerides) and change in systolic and diastolic blood pressure and platelet biomarkers of haemostatic function (proteomics).		6 months	No