Trial document





This trial has been registered retrospectively.
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  DRKS00008915

Trial Description

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Title

Influence of genetic polymorphisms on the plasma concentrations of oral tyramine applique - pharmacogenetics biogenic amines

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

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Brief Summary in Scientific Language

The group of biogenic amines includes a variety of substances that are formed in the human and animal organisms and in microorganisms as signaling molecules as intermediates in cellular metabolism or degradation products. A common feature of these compounds are aliphatic primary amino groups. Many biogenic amines are due to their charge characteristics not well capable of biological membranes and therefore have to be transported by specific transport proteins. Many of these substances have to be metabolized in the body to prevent damage by poisoning or de-regulation of signaling pathways. Major metabolic pathways of biogenic amines and the enzymes involved have been elucidated decades ago and are shown in corresponding textbooks of biochemistry and nutritional sciences. Amazingly, there are currently no human trials that address the question of how the absorption, distribution and excretion of biogenic amines, which are in the human body after receiving corresponding food, depend on genetic polymorphisms. According to tyramin, it was already shown more than 10 years aga that it is transported by the transport protein OCT1 into the liver cell and there then metabolized (Breidert, Spitzenberger et al. 1998). We were able to confirm the OCT1 mediated Transport in in-vitro laboratory experiments (Pereira et al., Unpublished), but nonetheless there remain doubts about whether in the living man OCT 1actually is the relevant transport protein for the elimination (Schömig , Lazar et al. 2006). This is not only a purely academic question, because it could, for example, explain why some people after ingestion of foods that contain biogenic amines, more than others occasionally or even regularly suffer from complaints (depending on the type of biogenic amines headache, nausea, changes in blood pressure or allergic reactions). In addition, there could be an important indication that some people could be charged more frequently at appropriate nutrients through food-drug interactions. The result of the study could provide guidance for limits of such substances in food materials, better than previous limits take into account the specific individual risks. A primary issue in the study is whether statistically significantly different blood concentrations of tyramine following oral administration of 400 mg tyramine differ between the genotypes of OCT1 and other potential candidates. Further exploratory edited questions concern corresponding differences in other biogenic amines, which can be measured at the same time and other hereditary polymorphic enzymes, transport proteins and components of signaling pathways, which for tyramine could play a role here as well.

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Organizational Data

  •   DRKS00008915
  •   2015/07/17
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  •   yes
  •   Approved
  •   19/8/13, Ethik-Kommission der Medizinischen Fakultät der Georg-August-Universität Göttingen
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Secondary IDs

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Health Condition or Problem studied

  •   Healthy participants
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Interventions/Observational Groups

  •   400 mg Tyramin orally once
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Pharmacogenetics
  •   Single (group)
  •   N/A
  •   N/A
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Primary Outcome

Area under the plasma concentration-time curve of tyramine for the first 6 hours after oral administration of 400 mg of tyramine depending on congenital genetic variants with significance for transport proteins, metabolizing enzymes and components relevant to the effects of biogenic amines pathways.

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Secondary Outcome

Plasma concentrations of tyramine before taking 400 mg tyramine, plasma concentrations and area under the plasma concentration-time curves of other endogenous and exogenous biogenic amines insofar as they are detectable (e.g. Adrenalin, Tryptamin, Noradrenalin, Putrescin, Isoamylamin, Dopamin, Cadaverin, Agmatin, Serotonin, Phenylethylamin, Isopropanolamin, Histamin, Spermidin, Cholin, Gamma-Aminobuttersäure, Octopamin, 5-Methoxyindol Ethylamin, Synephrin, 5-Methoxytryptamin, Colamin, Cysteamin, Beta-Alanin), in the urine excreted amounts of primary and secondary amines measured with and without enzymatic cleavage - each depending on congenital genetic variants with significance for transport proteins, metabolizing enzymes and components relevant to the effects of biogenic amines pathways.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2014/05/22
  •   100
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   50   Years
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Additional Inclusion Criteria

Subjects between 18 and 50 years of age. Body weight between 50 and 100 kg, while body mass index 18 to 30.

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Exclusion Criteria

Any known chronic disease significantly increasing cardiovascular risk profile. This is but not limited to: Diabetes mellitus, arterial hypertension, heart failure, status post myocardial infarction, Post-bypass OP or percutaneous transluminal angioplasty, Post-stroke, renovascular disease. Known intolerance to tyramine. Need for any regular medication other than oral contraceptives.

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Institut für Klinische PharmakologieUniversitätsmedizin Göttingen
    • Mr.  Prof. Dr. med.  Jürgen  Brockmöller 
    • Robert-Koch-Str. 40
    • 37075  Göttingen
    • Germany
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    • Universitätsmedizin GöttingenInstitut für Klinische Pharmakologie
    • Mr.  Prof. Dr. med.  Jürgen  Brockmöller 
    • Robert-Koch-Str. 40
    • 37075  Göttingen
    • Germany
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    • Institut für Klinische PharmakologieUniversitätsmedizin Göttingen
    • Mr.  Prof. Dr. med.  Jürgen  Brockmöller 
    • Robert-Koch-Str. 40
    • 37075  Göttingen
    • Germany
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Sources of Monetary or Material Support

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    • Forschungsgemeinschaft (DFG)
    • Kennedyallee 40
    • 53175   Bonn
    • Germany
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    • UniversitätsmedizinInstitut für Klinische PharmakologieGöttingen
    • Robert-Koch-Str. 40
    • 37075   Göttingen
    • Germany
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Status

  •   Recruiting ongoing
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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.