Monocentered, randomised, placebo-controlled, double-blind cross-over study on the effect of Conjugated Linoleic Acid (CLA) on fasting and postprandial metabolic parameters and endothelial function in men with PPARγ2 P12A polymorphism and controls

ISRCTN ISRCTN91188075
DOI https://doi.org/10.1186/ISRCTN91188075
Secondary identifying numbers N/A
Submission date
07/06/2007
Registration date
25/07/2007
Last edited
17/12/2009
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Other
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Juergen Schrezenmeir
Scientific

Bundesforschungsanstalt für Ernährung und Lebensmittel, Standort Kiel
Institut für Physiologie und Biochemie der Ernährung
Hermann-Weigmann-Str. 1
Kiel
24103
Germany

Phone +49 (0)431 609 2220
Email juergen.schrezenmeir@bfel.de

Study information

Study designRandomised, double-blind, placebo-controlled, interventional, crossover study.
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeNot Specified
Scientific title
Study acronymCLA2 (Conjugated linoleic acid 2)
Study objectivesConjugated Linoleic Acid (CLA) may beneficially affect lipid and glucose metabolism, inflammatory responses and body weight. These aspects are of relevance for subjects afflicted with or prone to develop so called “metabolic syndrome”, which is characterized by an insulin resistance, dyslipidaemia, essential hypertension and adiposity of the central type and frequently leads to early manifestation of type 2 diabetes mellitus, increased vascular risk and risk of atherosclerosis.

Studies of the influence of dietary CLA, namely the individual isomers cis9,trans11-CLA and trans10,cis12-CLA as well as the commercially available 50:50 mixture of these isomers, as compared to linoleic acid as control, on fasting and postprandial metabolism. The study will test if there are genotype-dependent specific effects of the PPARγ2 P12A polymorphism (P12P versus A12A homozygosity). Expression of genes relevant for inflammation and metabolic regulation will be examined in monocytes independent of a PPARγ2 polymorphism. Further parameters to assess atherogenic processes are the expression of adhesion molecules (ICAM, VCAM, E-Selectin). Low Density Lipoprotein (LDL) will be isolated and tested for adhesion molecules expression on endothelial cells. As another study reported that a mixture of CLA isomers impairs endothelial function, this parameter will be determined in our study, with particular attention for the effect of individual isomers. As dietary fats may acutely change endothelial function, this parameter is tested both in the fasting state and following a fat-rich meal. Genotype-dependent specific effects on fat tissue are to be examined by determining the gene expression profile of the subcutaneous fat tissue. Furthermore the effect of CLA on fecal flora will be assessed.
Ethics approval(s)Ethic Committee of the Medical Faculty of the Christian-Albrechts-University of Kiel, (Germany), approved on 13.09.2006 (ref: A151/06)
Health condition(s) or problem(s) studiedNot applicable
InterventionAll participants will consume, in random order, capsules with either the individual isomers cis9,trans11-CLA and trans10,cis12-CLA as well as the commercially available 50:50 mixture of these isomers, and linoleic acid as control. The material is provided as free fatty acids in capsules. Tocopherol content of the preparations is standardized.

Each intervention will last for 4 weeks, interrupted by wash-out periods of 6-9 weeks between the interventions.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Conjugated Linoleic Acid
Primary outcome measureChange of postprandial triglyceride levels (Area Under the Curve [AUC]) after 28 (±2) days supplementation. Postprandial triglyceride levels will be measured at the start of the study and after each intervention period.
Secondary outcome measuresMeasurements for the following will be made at the start of the study and after each intervention period.

Changes in:
1. Fasting and postprandial insulin (AUC)
2. Fasting and postprandial glucose (AUC)
3. Endothelial function (PAT-Index)
4. Body Mass Index (BMI)
5. Waist circumference (WC)
6. Waist to hip ratio (WHR)
7. Blood pressure, pulse
8. HOMA (Insulin-glucose-product)
9. Metabolic regulatory parameters, namely:
9.1. Glucose dependent insulinotropic polypeptide (GIP)
9.2. Adipsinresistin
9.3. Cholesteryl Ester Transfer Protein (CETP)
9.4. Adiponectin
9.5. Leptin
9.6. Cholezystokinin (CCK)
9.7. Acylation Stimulating Protein (ASP)
10.1. Lipids and apolipoproteins, namely:
10.2. VLDL, total
10.3. LDL- and HDL-cholesterol
10.4. Lipoprotein a (Lp [a])
10.5 Lipoprotein lipase (LpL)
10.6. Apoliprotein AI, AII, and B100
10.7. Fatty acid pattern in cholesteryl esters
10.8. Phospholipids
11. Oxidative modification of lipids and oxidative stress, namely:
11.1. Oxidised LDL
11.2. isoprostanes
11.3. LDL-induced adhesion molecule expression
11.4. Platelet-Activating Factor (PAF)
11.5. total glutathione in erythrocytes,paraoxonase
11.6. Platelet-Activating Factor AcetylHydrolase (PAF-AH)
12. Inflammatory parameters, namely:
12.1. C-reactive protein (CRP)
12.2. Vascular Cell Adhesion Molecule (VCAM)
12.3. InterCellular Adhesion Molecule (ICAM)
12.4. E-selectin, InterLeukin-6 (IL-6)
12.5. Tumor Necrosis Factor-α (TNFα)
12.6. Monocyte Chemoattractant Protein-1 (MCP-1)
12.7. Vascular Endothelial Growth Factor (VEGF)
13. Gene expression profile in adipocytes (fasting adipocyte biopsy) and monocytes (fasting monocyte isolation) by Random-Zell-RNA-assay: expression of genes which may affect lipid metabolism and inflammatory responses (arteriosclerosis)
14. Fecal flora
Overall study start date11/10/2006
Completion date12/07/2007

Eligibility

Participant type(s)Patient
Age groupAdult
SexMale
Target number of participants40
Key inclusion criteria1. Healthy male volunteers aged 45-68
2. Homozygosis of PPARγ2 P12A polymorphism
3. Member of the Metabolic Intervention Cohort Kiel (MICK)

BMI- matched controls will be recruited.
Key exclusion criteria1. Participation in a clinical study with a medicament or a medicinal product within the last 30 days or simultaneous participation in another clinical examination
2. Inability to understand and to comply with the study protocol
3. Known metabolic or gastro-intestinal diseases, which affect the absorption, metabolism or excretion of food or food components
4. Condition after surgery of the gastro-intestinal tract, which affect gastro-intestinal motility
5. Hemoglobin <12 g/dL
6. Latex allergy
7. Diabetes (fasting glucose levels >125 mg/dl after repeated determination)
8. Surgery within the last 3 months, which still affects the current state of health
9. Intake of nitrate and/or calcium antagonists and/or alpha-blockers, which affect the blood pressure
10. Deformation of finger tips, which inhibits correct recording of EndoPAT
11. Illness of thyroid gland, which has metabolic and/or cardiovascular effect
12. Known hepatitis B, hepatitis C, HIV infection or chronic liver damage
13. Kidney insufficiency
14. Drug or alcohol abuse
15. Intake of drugs affecting the absorption, metabolism or excretion of food components or the gastro-intestinal motility
16. Intake of hormone preparations, particularly cortisone
17. Eating disorders, anorexia, bulimia, unusual outsider dietary habits
18. Psychiatric disorders, epilepsy, risk of suicide
19. For those who participate in adipose tissue biopsy, additionally:
19.1. Known allergies against local anaesthetics
19.2. Heart insufficiency
19.3. Coagulation dysfunction/consumption of drugs which may cause such dysfunctions
Date of first enrolment11/10/2006
Date of final enrolment12/07/2007

Locations

Countries of recruitment

  • Germany

Study participating centre

Bundesforschungsanstalt für Ernährung und Lebensmittel, Standort Kiel,
Kiel
24103
Germany

Sponsor information

Federal Research Centre for Nutrition and Food (BfEL) (Germany)
Government

Haid-und-Neu-Str. 9
Karlsruhe
76131
Germany

Email pbe.kiel@bfel.de
Website http://www.bfel.de
ROR logo "ROR" https://ror.org/045gmmg53

Funders

Funder type

Government

Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung) (Germany)
Government organisation / National government
Alternative name(s)
Federal Ministry of Education and Research, BMBF
Location
Germany
Federal Ministry of Food, Agriculture and Consumer Protection (Bundesministerium für Ernährung, Landwirtschaft und Verbraucherschutz) (Germany)

No information available

Cognis GmbH (Germany)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 18/08/2009 Yes No