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

Organizational Data

DRKS-ID:
DRKS00008915
Recruitment Status:
Recruiting ongoing
Date of registration in DRKS:
2015-07-17
Last update in DRKS:
2015-07-17
Registration type:
Retrospective

Acronym/abbreviation of the study

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URL of the study

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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 We were able to confirm the OCT1 mediated Transport in in-vitro laboratory experiments (Pereira et al., Unpublished), but nonetheless there remain doubts about whether in the living man OCT 1actually is the relevant transport protein for the elimination (Schömig , Lazar et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.

Health condition or problem studied

Free text:
Healthy participants
Healthy volunteers:
No Entry

Interventions, Observational Groups

Arm 1:
400 mg Tyramin orally once

Endpoints

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.
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.

Study Design

Purpose:
Pharmacogenetics
Allocation:
N/A (single arm study)
Control:
  • Uncontrolled/single arm
Phase:
N/A
Study type:
Interventional
Mechanism of allocation concealment:
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Blinding:
No
Assignment:
Single (group)
Sequence generation:
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Who is blinded:
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Recruitment

Recruitment Status:
Recruiting ongoing
Reason if recruiting stopped or withdrawn:
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Recruitment Locations

Recruitment countries:
  • Germany
Number of study centers:
Monocenter study
Recruitment location(s):
  • University medical center Institut für Klinische Pharmakologie Göttingen

Recruitment period and number of participants

Planned study start date:
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Actual study start date:
2014-05-22
Planned study completion date:
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Actual Study Completion Date:
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Target Sample Size:
100
Final Sample Size:
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Inclusion Criteria

Sex:
All
Minimum Age:
18 Years
Maximum Age:
50 Years
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.

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.

Addresses

Primary Sponsor

Institut für Klinische PharmakologieUniversitätsmedizin Göttingen
Prof. Dr. med. Jürgen Brockmöller
Robert-Koch-Str. 40
37075 Göttingen
Germany
Telephone:
+49 551 39 5770
Fax:
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Contact per E-Mail
URL:
No Entry
Investigator Sponsored/Initiated Trial (IST/IIT):
Yes

Contact for Scientific Queries

Universitätsmedizin GöttingenInstitut für Klinische Pharmakologie
Prof. Dr. med. Jürgen Brockmöller
Robert-Koch-Str. 40
37075 Göttingen
Germany
Telephone:
+49 551 39 5770
Fax:
No Entry
Contact per E-Mail
URL:
No Entry

Contact for Public Queries

Institut für Klinische PharmakologieUniversitätsmedizin Göttingen
Prof. Dr. med. Jürgen Brockmöller
Robert-Koch-Str. 40
37075 Göttingen
Germany
Telephone:
+49 551 39 5770
Fax:
No Entry
Contact per E-Mail
URL:
No Entry

Principal Investigator

Universitätsmedizin GöttingenInstitut für Klinische Pharmakologie
Prof. Dr. med. Jürgen Brockmöller
Robert-Koch-Str. 40
37075 Göttingen
Germany
Telephone:
+49 551 39 5770
Fax:
No Entry
Contact per E-Mail
URL:
No Entry

Sources of Monetary or Material Support

Public funding institutions financed by tax money/Government funding body (German Research Foundation (DFG), Federal Ministry of Education and Research (BMBF), etc.)

Forschungsgemeinschaft (DFG)
Kennedyallee 40
53175 Bonn
Germany
Telephone:
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Fax:
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Contact per E-Mail
URL:
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Institutional budget, no external funding (budget of sponsor/PI)

UniversitätsmedizinInstitut für Klinische PharmakologieGöttingen
Robert-Koch-Str. 40
37075 Göttingen
Germany
Telephone:
No Entry
Fax:
No Entry
Contact per E-Mail
URL:
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Ethics Committee

Address Ethics Committee

Ethikkommission der Universitätsmedizin Göttingen
Von-Siebold-Straße 3
37075 Göttingen
Germany
Telephone:
+49-551-3961261
Fax:
+49-551-3969536
Contact per E-Mail
URL:
No Entry

Vote of leading Ethics Committee

Date of ethics committee application:
2013-08-02
Ethics committee number:
19/8/13
Vote of the Ethics Committee:
Approved
Date of the vote:
2013-12-16

Further identification numbers

Other primary registry ID:
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EudraCT Number:
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UTN (Universal Trial Number):
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EUDAMED Number:
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IPD - Individual Participant Data

Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
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IPD Sharing Plan:
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Study protocol and other study documents

Study protocols:
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Study abstract:
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Other study documents:
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Background literature:
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Related DRKS studies:
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Publication of study results

Planned publication:
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Publikationen/Studienergebnisse:
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Date of first publication of study results:
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DRKS entry published for the first time with results:
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Basic reporting

Basic Reporting / Results tables:
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Brief summary of results:
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