Trial document




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  DRKS00015619

Trial Description

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Title

Impact and function of the mitochondria transcription factor A (TFAM) in sepsis

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

Sepsis is still one of the most frequent causes of death in intensive care units, but the pathomechanisms are not fully understood. A main reason for high death frequency is the mitochondrial dysfunction. The mitochondria are the powerhouse of our cells. If the function of these mitochondria is impaired, the cells can´t produce enough energy to survive. This leads up to organ failure. One protein, called mitochondrial transcription factor A (TFAM), is so important for the mitochondria. The mitochondria can not work without TFAM. The role of TFAM is still unknown during sepsis.
The purpose of this study is to investigate, how TFAM influences the sepsis. It could give us a new therapeutic option. This may help to treat people with blood poisining faster and better.

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Brief Summary in Scientific Language

Sepsis is one of the most frequent causes of death in intensive care units and it is caused by a misdirected immune reaction which leads to a life-threatening organ dysfunction.
The pathophysiological mechanisms that cause numerous functional changes during sepsis are not fully understood yet. The mitochondria play an important role in the pathophysiological context of sepsis or inflammation.

The aim of the study is to detect the mitochondrial dysfunction, especially the mitochondrial transcription factor A (TFAM), which could be a key protein during sepsis.

To this end a lipopolysaccharide-based in vitro inflammation model is used and the experiments are validated by septic patients. With this approach we want to elucidate if TFAM influences pathophysiological changes of sepsis.

Methods: Full blood is collected from 20 healthy volunteers. Peripheral mononuclear blood cells (PMBCs) are stimulated by LPS. The mitochondrial and cytosolic proteins are isolated. The concentration of TFAM in the mitochondria and in the cytsol are examined using western blot.
In addition, nuclear proteins, RNA and DNA are extracted from the cells in order to quantify the expression of the proteins, which regulate the expression of TFAM. The important regulation proteins are NFkB, PGC-1α, NRF1 and NRF2. For the quantification of the abovementioned proteins, Elisa and RT-PCR are used.
The experiments are validated by septic patients.

The aim of the study is to better understand the pathophysiology of sepsis. It might provide information on whether TFAM plays a key role during sepsis. Beyond that, it could give us a new therapeutic option.

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Organizational Data

  •   DRKS00015619
  •   2018/10/08
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  •   yes
  •   Approved
  •   18-6257, Ethik-Kommission der Medizinischen Fakultät der Ruhr-Universität Bochum
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Secondary IDs

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Health Condition or Problem studied

  •   A41.9 -  Sepsis, unspecified
  •   healthy volunteers
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Interventions/Observational Groups

  •   Full blood is collected from 20 healthy volunteers. Peripheral mononuclear blood cells (PMBCs) are examined for mitochondrial dysfunction after LPS stimulation during the time courses (after 1/2, 4, 24, 48 hours). One fraction of PBMCs are not stimulated and are used as references.

    In addition, nuclear, mitochondrial and cytosolic proteins as well as RNA and DNA are extracted from the cells in order to quantify the expression of TFAM and the proteins, which regulate the expression of TFAM. The important regulation proteins are NFkB, PGC-1α, NRF1 and NRF2.
  •   The experiments are validated by septic patients.
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Characteristics

  •   Interventional
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  •   Non-randomized controlled trial
  •   Open (masking not used)
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  •   Other
  •   Basic research/physiological study
  •   Other
  •   N/A
  •   N/A
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Primary Outcome

Evaluation of the ratio of the mitochondrial and cytosolic concentration of TFAM beofre LPS stimulation and after LPS stimualtion during the time course (after 1/2, 4, 24, 48 hours) by western blot.

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Secondary Outcome

Evalutaion of the expression of mitochondrial mRNA, mRNA of TFAM and the regulation proteins (NFkB, PGC-1α, NRF1, NRF2) during the time course (after 1/2, 4, 24, 48 hours) by RT-PCR and Elisa.
Furthermore the different TFAM Expression and distribution will be observerd in surivors compared to non-survivors after 30 days.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2018/09/10
  •   30
  •   Monocenter trial
  •   National
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Inclusion Criteria

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

voluntary; healthy individuals age >18, <65, no risk for blood drawing

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Exclusion Criteria

low body weight (< 50 kg), too young age <18 and too old age>65, anemia, anamnestic incompatibility of blood drawing

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Addresses

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    • Universitätsklinikum Knappschaftskrankenhaus Bochum
    • Mr.  Prof.  Michael  Adamzik 
    • In der Schornau 23-25
    • 44892  Bochum
    • Germany
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    • Ruhr Universität Bochum Knappschaftskrankenhaus Bochum Klinik für Anästesiologie
    • Ms.  Dr  Katharina  Rump 
    • Universitätsstraße 150
    • 44801  Bochum
    • Germany
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    • Universitätsklinikum Knappschaftkrankenhaus Bochum GmbH Klinik fürAnästhesiologie, Intensivmedizin und Schmerztherapie
    • Mr.  Dr.  Tim  Rahmel 
    • In der Schornau 23-25
    • 44892  Bochum
    • Germany
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Sources of Monetary or Material Support

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    • Ruhr-Universität Bochum
    • Universitätsstr. 150
    • 44801  Bochum
    • Germany
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    • Universitätsklinikum Knappschaftskrankenhaus Bochum Klinik fürAnästhesiologie, Intensivmedizin und Schmerztherapie
    • Mr.  Dr  Tim  Rahmel 
    • In der Schornau 23-25
    • 44892  Bochum
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2019/01/21
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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.