Conjugated Linoleic Acid Supplementation Study (CLASS)
Recruitment status was Active, not recruiting
Cardiovascular disease is a major cause of mortality worldwide resulting in one out of three global deaths. One of the main characteristics of cardiovascular disease is impaired blood flow and increased formation of clots. Platelets are clot-forming cells responsible for prevention of bleeding. However, in disease state they may be overly activated and tend to stick to each other, promoting blood clots and blockage of vessels.
Conjugated linoleic acids (CLA) are unique fatty acids present in dairy food products and beef which would help to prevent platelets from clotting and thus help to prevent cardiovascular disease. However, the mechanisms by which those fatty acids affect platelet function are not yet fully understood. We designed a human intervention study assessing the mechanisms by which CLA beneficially affect platelet function and markers of haemostasis and inflammation in humans.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Effects of cis9,trans11 Conjugated Linoleic Acid on Platelet Function, Markers of Haemostasis and Inflammation on Humans|
- Change of expression of P-selectin and fibrinogen receptor activation on platelets by flow cytometry [ Time Frame: At 2 weeks ] [ Designated as safety issue: No ]Using fluorescently-conjugated monoclonal antibodies and whole blood flow cytometry after ex vivo stimulation with adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP) P-selectin expression as early marker of platelet activation Activated fibrinogen receptor as late marker of platelet activation
- Change of in vitro bleeding time using the Platelet Function Analyzer (PFA-100) [ Time Frame: At 2 weeks supplementation ] [ Designated as safety issue: No ]Using collagen-epinephrine coated cartridges Using collagen-adenosine diphosphate coated cartridges
- Change of coagulation marker assessed as fibrinogen levels in plasma [ Time Frame: At 2 weeks supplementation ] [ Designated as safety issue: No ]Using semi-automated coagulometer using fibrinogen assay according to Clauss method
- Change in light transmission aggregometry of platelet rich plasma induced by collagen and arachidonic acid [ Time Frame: At 2 weeks supplementation ] [ Designated as safety issue: No ]Using a Helena Platelet Aggregation Chromogenic Kinetics System-4 (PACKS-4) light transmission aggregometer
- Change in plasma levels of von Willebrand factor (vWF), soluble ICAM (s-ICAM) and soluble P-selectin (sP-selectin) as markers of endothelial activation [ Time Frame: At 2 weeks supplementation ] [ Designated as safety issue: No ]Using enzyme-linked immunoabsorbent assay (ELISA) in plasma
|Study Start Date:||November 2010|
|Estimated Study Completion Date:||November 2012|
|Estimated Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Active Comparator: cis9,trans 11 CLA oil
50 volunteers on cross over design , receiving 4g/day of cis9,trans11 CLA
Dietary Supplement: Placebo oil
Placebo oil of 4g/day
Placebo Comparator: Placebo oil
50 volunteers cross over design, placebo oil 4g/day
Dietary Supplement: Placebo oil
Placebo oil of 4g/day
Despite being trans fatty acids, dietary conjugated linoleic acids( CLA) have been associated with decreased atherogenesis, beneficial effects on insulin sensitivity , glucose and lipid profile and body composition in animal studies.Todate only few studies have studied the effects of the two individual CLA isomers on body composition , lipoprotein metabolism immune function , inflammation , insulin sensitivity and oxidative stress in humans.
A previous study revealed that both cis9,trans11 and trans10,cis12 CLA, as well as CLA mix, significantly decreased agonist-induced platelet aggregation and TxB2 production ex vivo compared with linoleic acid. No effect on agonist-induced platelet aggregation or other blood clotting parameters in healthy female volunteers was observed upon supplementation with 3.9 g/d CLA, compared with sunflower oil, but this may have been due to the low number of subjects participating in this study.
Indeed, supplementation with 13.0 g/day of CLA mix - 50:50 blend, compared with placebo oil, significantly decreased fibrinogen levels in type 2 diabetes patients, and fibrinogen and plasminogen activator inhibitor-1 levels were significantly lower upon intervention with CLA milk (4.7 g/d cis9,trans11 CLA and 0.4 g/d trans10,cis12 CLA), compared with CLA mix (2.3 g/d cis9,trans11 CLA and 2.2 g/d trans10,cis12 CLA), and lower compared with olive oil, in postmenopausal women.Thus overall evidence indicates that especially the cis9,trans11 CLA isomer may prevent platelet activation and aggregation, and possibly display anticoagulant properties. However, so far this has not been assessed in detail.
In this study we assess effects of supplementation of cis9,trans11 CLA-rich oil on platelet function by measuring not only platelet aggregation but also in vitro coagulation and platelet activation in healthy overweight humans. In addition, we examine the effects of CLA supplementation on plasma and cellular marker of inflammation and oxidative stress.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01234636
|Rowett Institute of Nutrition and Health|
|Aberdeen, Scotland, United Kingdom, AB21 9SB|
|Principal Investigator:||Baukje De Roos, PhD||Univeristy of Aberdeen|