Trial document




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  DRKS00005144

Trial Description

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Title

Human low density lipoprotein-metabolism in silico: Modeling the change of lipid-composition in the lipoprotein particle

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language


Lipoproteins especially low density lipoprotein (LDL) are associated to cardiovascular diseases. Lipoproteins are lipid-protein-complexes, wich mediate the transport of lipids via plasma. The aim of this study is to describe the LDL metabolism with a mathematical model. The dynamics of LDL- lipids and the relevant enzymes are key determinats. For the parametrisation of the model a singular fasting blood draw of six healthy probands is provided.
Human plasma is incubated after drawing at 37° Celsius. Certain but not all enzymes work on as in vivo. Next parameters of the fat metabolism are measured, to estimate the enzyme activity with a mathematical model.

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Brief Summary in Scientific Language

The lipoprotein metabolism is associated to cardiovascular diseases, which are due to their high frequency in western societies of enormous medical interest. Especially the LDL-cholesterol concentration and the LDL-subfraction pattern are important markers for the risk of a cardiovascular event. Main components of LDL are free- and esterified-cholesterol (FC, CE), triglycerides (TG), phospholipids (PL) and Apolipoprotein B-100 (ApoB). LDL particles are modified in plasma by several reactions. Our aim is to enlighten the dependence between the LDL composition and subfraction pattern, and the reactions associated to LDL by developing a model describing the dynamics of the components in LDL subfractions given a set of reaction rates.
We want to incubated fasting plasma of six voluntary donors at 37°Celsius for 0, 1 and 4 hours before isolating LDL subfractions. We expect significant changes in the LDL composition after the incubation. As in vitro only the enzymes cholesterylester transfer protein (CETP) and Lecithin—cholesterol acyltransferase (LCAT) are available for LDL particle TG and CE modulation, their activity could be well estimated under the model assumptions. Additionally assuming that all LDL particles in fasting plasma have the same clearance rate, it should be possible to estimate the activities of other enzymes like hepatic lipases (HL), which are not available in the in vitro situation.
We want to develop a method to model the dynamics of TG, CE and FC dynamics in LDL. Only simple lipid concentration measurement in lipoprotein subfractions is necessary. The model could be used to predict the net fluxes of TG and CE in LDL. Furthermore the effect of changes of certain enzyme activities on the composition of LDL-subfractions could be computed. LCAT, HL or CETP activity can also be measured clinical. Hence the here presented method could offer a relative simple alternative.

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Organizational Data

  •   DRKS00005144
  •   2013/08/12
  •   [---]*
  •   yes
  •   No approval required according to EC
  •   [---]*, Ethik-Kommission der Albert-Ludwigs-Universität Freiburg
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Secondary IDs

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Health Condition or Problem studied

  •   healthy participants
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Interventions/Observational Groups

  •   Venous blood-plasma is drawn from healthy probands, who were fasting for 10 hours and have a normal lipoprotein-metabolism, which is not perturbed by medication. The plasma is incubated for different time intervals at 37°C in an incubation chamber
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Characteristics

  •   Non-interventional
  •   Other
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Basic research/physiological study
  •   Single (group)
  •   N/A
  •   N/A
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Primary Outcome

Lipid- and apolipoprotein-concentrations before and after incubation in 6 LDL-subfractions. Established methods are used.
Lipids:
triglycerides,
total cholesterol,
free cholesterol,
phospholipids.
Apolipoproteins:
Apolipoprotein B-100,
Apolipoprotein A-I,
Apolipoprotein A-II,
Apolipoprotein E,
Lipoprotein LP(a)

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Secondary Outcome

Lipid- and apolipoprotein-concentrations before and after incubation in VLDL, IDL and three HDL-subfractions. Established methods are used.
Lipids:
triglycerides,
total cholesterol,
free cholesterol,
phospholipids.
Apolipoproteins:
Apolipoprotein B-100,
Apolipoprotein A-I,
Apolipoprotein A-II,
Apolipoprotein E,
Lipoprotein LP(a)

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Planned
  •   2013/08/26
  •   6
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   20   Years
  •   55   Years
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Additional Inclusion Criteria

20-55 years normolipidemic

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Exclusion Criteria

use of statins,
impaired lipoprotein-metabolism

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Universitätsklinikum Freiburg
    • Mr.  Prof. Dr.  Karl  Winkler 
    • Hugstetter Strasse 55
    • 79106  Freiburg
    • Germany
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    • Univeritätsklinikum Freiburg
    • Mr.  Dipl. math.  Martin  Jansen 
    • Hugstetter Str. 55
    • 79106  Freiburg
    • Germany
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    • Univeritätsklinikum Freiburg
    • Mr.  Dipl. math.  Martin  Jansen 
    • Hugstetter Str. 55
    • 79106  Freiburg
    • Germany
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Sources of Monetary or Material Support

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    • Universitätsklinikum Freiburg Institut für klinische Chemie und Laboratoriumsmedizin
    • Hugstetter Strasse 55
    • 79106  Freiburg
    • Germany
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.