Conjugated Linoleic Acid Supplementation Study (CLASS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by:
University of Aberdeen
ClinicalTrials.gov Identifier:
NCT01234636
First received: November 2, 2010
Last updated: November 7, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention
Cardiovascular Disease
Dietary Supplement: Placebo oil

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Aberdeen:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 50
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)
Arms Assigned Interventions
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   30 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:• Healthy men and women aged 35-74 years

  • blood pressure below 160/90 mmHg;
  • fasting plasma glucose < 7 mmol/L;
  • total cholesterol < 8 mmol/L,with cholesterol/HDL ratio < 6 and/or ASSIGN score < 20%)
  • platelet count > 170x109/L
  • haematocrit above 40 % for males and above 35 % for females
  • haemoglobin above 130 g/L for males and above 115 g/L for females
  • having a 10-20% risk for developing cardiovascular disease within the next 10 years based on the ASSIGN calculation (http://cvrisk.mvm.ed.ac.uk/index.htm) including the following factors: age, gender, number of cigarettes smoked per day, Scottish Index of Multiple Deprivation (SIMD)/postcode, systolic blood pressure, levels of total and HDL cholesterol and family history of cardiovascular disease or having at least one additional risk factor such as being over 50 years old, BMI above 25 kg/m2, elevated triglyceride levels (> 1.7 mmol/L) or elevated glucose levels (> 5.6 mmol/L);

Exclusion Criteria:Exclusion criteria Subjects are excluded if

  • They are regularly taking aspirin or aspirin-containing drugs, or other anti-inflammatory drugs;
  • They are taking drugs or herbal medicines known to alter platelet function or the haemostatic system in general;
  • They are diagnosed with diabetes, hypertension, renal, hepatic, haematological disease or coronary heart disease;
  • They are undertaking more than 6 hours vigorous exercise per week
  • They are pregnant (or planning to become pregnant) or lactating;
  • They have given a pint of blood for transfusion purposes within the last month;
  • They have unsuitable veins for blood sampling;
  • They are inability to understand the participant information sheet or inability to speak, read and understand the English language.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01234636

Locations
United Kingdom
Rowett Institute of Nutrition and Health
Aberdeen, Scotland, United Kingdom, AB21 9SB
Sponsors and Collaborators
University of Aberdeen
Investigators
Principal Investigator: Baukje De Roos, PhD Univeristy of Aberdeen
  More Information

Publications:

Responsible Party: Dr. Baukje de Roos, Univeristy of Aberdeen, Rowett Institute of Nutrition and Health, Univeristy of Aberdeen
ClinicalTrials.gov Identifier: NCT01234636     History of Changes
Other Study ID Numbers: RINH_1000
Study First Received: November 2, 2010
Last Updated: November 7, 2012
Health Authority: UK:North of Scotland research ethics Service.

Keywords provided by University of Aberdeen:
Platelets
Platelet aggregation
Platelet activation
Platelet function
Light transmission aggregometry
Flow cytometry
Platelet function analyzer-100 (PFA-100)
Linoleic acid, conjugated
cis9, trans11 conjugated linoleic acid
dietary supplement
short-term intervention

Additional relevant MeSH terms:
Cardiovascular Diseases

ClinicalTrials.gov processed this record on October 23, 2014