Trial to Assess the Effects of Different Trans-fatty Acids on Endothelial Function in Humans

This study has been terminated.
(Recruitment problems)
Sponsor:
Collaborators:
Agroscope Liebefeld-Posieux Research Station ALP
University of Bern
Schweizerische Herzstiftung
Bundesamt für Landwirtschaft
Emmi Schweiz AG
Information provided by:
University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier:
NCT00933322
First received: July 2, 2009
Last updated: July 11, 2013
Last verified: July 2013

July 2, 2009
July 11, 2013
July 2009
June 2013   (final data collection date for primary outcome measure)
endothelial function using flow-mediated dilation [ Time Frame: 3 time points over 6 weeks (after 0, 2, 6 weeks) ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00933322 on ClinicalTrials.gov Archive Site
  • inflammation parameters in blood samples [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • coagulation parameters in blood samples [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • blood lipids in blood samples [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • adhesion molecules in blood samples [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • insulin resistance via blood samples [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Trial to Assess the Effects of Different Trans-fatty Acids on Endothelial Function in Humans
Randomized-controlled Trial to Assess the Effects of Different Trans-fatty Acids on Endothelial Function in Humans

The aim of the study is to compare a diet rich in trans fatty acids (TFA) from ruminant sources with a diet rich in TFA from hydrogenated vegetable oils (PHVO) in regard to their effects on cardiovascular risk markers (endothelial function, blood lipids, inflammation and coagulation parameters in the blood).

After a two week run-in period (diet without TFA) volunteers are randomized into three groups with different diets: diet rich in TFA from ruminant sources, diet rich in TFA from PHVO and diet without TFA. The intervention period lasts four weeks.

A nutritionist introduces the basic issues of the study diets. All volunteers supply themselves according to the recommendations of the Swiss food pyramid. Fat free food can be chosen individually in the context of defined guidelines. The amount and source of the fat in the diet are strictly defined. During the whole study, volunteers meet the nutritionist every 2 weeks, and in the weeks between, the volunteers are contacted by phone.

The volunteers will continue their normal daily life and physical activities. At the beginning of the run-in period and at the beginning and the end of the intervention period the endothelial function of the brachial artery will be assessed using flow-mediated dilation (FMD)/nitro-mediated dilation (NMD) methods and blood samples will be collected to analyze blood lipids, inflammation and coagulation parameters in the blood.

Hypothesis:

  1. Diet enriched with ruminant TFA has not the same negative effect on cardiovascular risk markers as diet enriched with the same amount of industrial TFA compared with a diet without TFA.
  2. Diet enriched with ruminant TFA has not a more negative effect on cardiovascular risk markers as diet without TFA.

Background:

For some time already negative effects of trans fatty acids (TFA) on the cardiovascular system are known. The main TFA sources in our nutrition are partly hydrogenated vegetable oils (PHVO) which result from partially oil hardening.

TFA also occur naturally in ruminant fat (meat, milk and their products). Epidemiologic studies suggest that not all TFA have the same negative effects on the cardiovascular system.

As the detrimental effect of TFA from PHVO is unquestioned (Mozaffarian et al. 2006, Ascherio et al. 1999), TFA from ruminant origin may have a neutral or positive effect on the cardiovascular system (Pfeuffer und Schrezenmeir 2006, Willett et al. 1993). The main reason is attributed to the different concentrations of TFA-isomers in the fat depending on the origin. Partially hydrogenated vegetable oils contains a high amount of elaidic acids (trans-9 18:1 isomer) and trans-10 18:1 isomers. Ruminant fats contain a high amount of vaccenic acids (trans-11 18:1 isomer). The vaccenic acid can be converted to the harmless conjugated linoleic acid (CLA) in the human and ruminant metabolic system.

TFA from PHVO have a negative effect on blood lipids and markers of the inflammatory system. They increase the Low Density Lipoproteins (LDL) and decrease the High Density Lipoproteins (HDL). Markers of the inflammatory system as TNFa Receptors, IL-6 and CRP increase with TFA consumption (Mensink et al. 2003; Mozaffarian 2006; Mozaffarian et al. 2009).

The discussion on the effect of TFA on insulin sensitivity is discussed conversely since there exists few studies which show different results. The trend indicates an impairment of insulin sensitivity with TFA consumption, particularly in predisposed persons (Hu 2001; Mozaffarian 2009; Risérus 2006).

Other studies indicated a negative effect on vessels' endothelial function and increase the level of soluble adhesion molecules (ICAM, VCAM) which are markers of endothelial dysfunction (Mozaffarian 2006; Mozaffarian et al. 2006).

Almost every typical risk factors of cardiovascular diseases induce changes in endothelial function which can preclinically be detected.

The analysis of endothelial function using endothelium-dependent flow-mediated dilation (FMD)and endothelium-independent vasodilation with nitroglycerin (NMD) of the brachial artery is a valuable, non-invasive method to determine the influence of various factors on the endothelial function (Moens et al. 2005).

Since changes in periphery are consistent with changes in the coronary vessels (Anderson et al. 1995), FMD represent a valuable indicator for cardiac events (Gokce et al. 2002, 2003; Widlansky et al. 2003). FMD is defined as percentage increase in vessel diameter from baseline conditions to maximum vessel diameter during hyperaemia (de Roos et al. 2003a).

Previous comparisons between TFA from ruminants and PHVO in clinical studies were only focused on changes in blood lipids (Chardigny et al. 2008, Motard-Bélanger et al. 2008).

Blood lipids are important factors concerning the risk of cardiovascular diseases, but not the only one as epidemiological and clinical studies indicated.

Studies on the effect of TFA on endothelial function, as well as on inflammatory and coagulation markers in the blood, become more important.

Objective:

The aim of the study is to compare a diet rich in trans fatty acids (TFA) from ruminant sources with a diet rich in TFA from hydrogenated vegetable oils (PHVO) in regard to their effects on cardiovascular risk markers (endothelial function, blood lipids, inflammation and coagulation parameters in the blood).

Methods:

Randomized, controlled, double blind study with healthy volunteers of both sex, aged between 45-65y. About 200 volunteers will be enrolled and randomized into 3 parallel study arms after a run-in period of 2 weeks.

Group 1 will follow a diet with 2% TFA of the total energy consumption from ruminant source, group 2 a diet with 2E% TFA from PHVO and group 3 a diet without any TFA for 4 weeks.

At the beginning of the run-in period and at the beginning and the end of the intervention period the endothelial function of the brachial artery will be assessed using flow-mediated dilation (FMD)/ nitro-mediated dilation (NMD) methods and blood samples will be collected to analyse blood lipids, inflammation and coagulation parameters in the blood. Nutrition councils will be passed at the beginning of the run-in period and then every 2 weeks. In the weeks between, the volunteers are contacted by phone.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Healthy
  • Dietary Supplement: diet enriched with industrial trans fatty acids
    After run-in phase of 2 weeks with margarine without TFA, 4 weeks with margarine enriched with industrial trans fatty acids following. TFA-percentage of total energy consumption is 2% or 6% of total fat energy consumption.
  • Dietary Supplement: diet enriched with ruminant trans fatty acids
    After run-in phase of 2 weeks with margarine without TFA, 4 weeks with butter enriched with ruminant trans fatty acids following. TFA-percentage of total energy consumption is 2% or 6% of total fat energy consumption.
  • Dietary Supplement: diet without any trans fatty acids
    6 weeks with margarine without any trans fatty acids.
  • Active Comparator: ruminant TFA
    In addition to the basic diet, volunteers enrich their diet with an individually calculated amount of butter containing ruminant TFA and with 15-20g rape oil for balancing the essential fatty acids.
    Intervention: Dietary Supplement: diet enriched with ruminant trans fatty acids
  • Active Comparator: industrial TFA
    In addition to the basic diet, volunteers enrich their diet with an individually calculated amount of butter containing TFA from PHVO and with 15-20g rape oil for balancing the essential fatty acids.
    Intervention: Dietary Supplement: diet enriched with industrial trans fatty acids
  • Placebo Comparator: without TFA
    In addition to the basic diet, volunteers enrich their diet with an individually calculated amount of butter without TFA and with 15-20g rape oil for balancing the essential fatty acids.
    Intervention: Dietary Supplement: diet without any trans fatty acids

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
142
June 2013
June 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • age 45-69
  • body mass index 20-30 kg/m2
  • willingness to hold physical activity constant over study duration
  • written informed consent

Exclusion Criteria

  • smoking
  • hypertension (> 140/90 mm Hg)
  • hypotension (men < 115 mm Hg; women < 105 mm Hg)
  • obesity (BMI =/> 30 kg/m2)
  • vegan
  • infections in the last 6 weeks
  • allergy for food (e.g., milk)
  • pregnancy
  • diabetes (elevated fasting blood glucose level)
  • clinical known coronary diseases
  • acute and/or chronical medication (incl. contraceptive)
  • abnormal kidney function
  • abnormal liver function
  • known cardiac arrhythmia (e.g., atrial fibrillation)
  • blood parameters (ALAT, Creatinin, Hb, potassium, CRP) in range
Both
45 Years to 69 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Switzerland
 
NCT00933322
KEK 124/09
Yes
Hugo Saner/ Prof. Dr. med, Bern University Hospital
University Hospital Inselspital, Berne
  • Agroscope Liebefeld-Posieux Research Station ALP
  • University of Bern
  • Schweizerische Herzstiftung
  • Bundesamt für Landwirtschaft
  • Emmi Schweiz AG
Study Director: Hugo Saner, Prof. Dr. med Cardiovascular Prevention and Rehabilitation, University Hospital Bern, Switzerland
Study Director: Alexandra Schmid, Dipl. oec. troph. Agroscope Liebefeld-Posieux Research Station ALP, Posieux, Switzerland
Principal Investigator: Thomas Radtke, MSc Cardiovascular Prevention and Rehabilitation, University Hospital Bern, Switzerland
University Hospital Inselspital, Berne
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP