Trial document




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  DRKS00008981

Trial Description

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Title

The role of heme oxygenase 1 (HO-1) for hematoma resolution, neuroinflammation and clinical outcome after subarachnoid hemorrhage (SAH)

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Trial Acronym

The role of heme oxygenase 1 in subarachnoid hemorrhage

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URL of the Trial

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Brief Summary in Lay Language

In this clinical trial we aim to study patients with a special form of brain bleeding. This special form of brain bleeding usually occurs after rupture of an enlarged brain vessel with accumulation of blood in the so called subarachnoid space. This space is usually filled with fluid that has the important role of protecting and nurturing the brain. Blood accumulation in this space leads to increased brain pressure and inflammation, both of which can lead to brain damage. Fast removal of the accumulated blood via the body's enzyme heme oxygenase-1 (HO-1) is of crucial importance in this situation. In patients with this special form of brain bleeding we aim to draw blood and brain fluid samples from existing drainage tubes at three different time points (day 1, day 7, day 14). HO-1 activity and inflammation will be determined in these samples and compared to the brain bleeding volume and neurological outcome. Furthermore, we aim to analyze additional clinical parameters that are known to predict neurological outcome. Primary endpoint is HO-1 activity in relation to the long-term brain function after bleeding. Secondary endpoints are HO-1 activity in relation to the bleeding size, inflammation and in relation to the additional predictors studied.
Hypothesis 1: HO-1 enzyme activation is associated with improved brain function after bleeding.
Hypothesis 2: The extend of HO-1 enzyme activation in the brain fluid is related to the bleeding volume.
Hypothesis 3: HO-1 activation reduces inflammation in the brain.
Hypothesis 4: The extend of HO-1 activation can predict brain function after bleeding.

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Brief Summary in Scientific Language

In this clinical trial we aim to study patients with non-traumatic, aneurysmal subarachnoid hemorrhage (SAH). Activity and expression of the enzyme heme oxygenase-1 (HO-1) could be from crucial importance for hematoma resolution after SAH. From the existing drainage tubes that the patients received for treatment and diagnostics, cerebrospinal fluid and blood will be drawn at three time points after hemorrhage occurred (day 1, day 7, day 14) with subsequent ex vivo analysis using molecular biology and standard laboratory tests to determine expression and activity of the heme oxygenase-1 enzyme (HO-1) and inflammatory markers in the cerebrospinal fluid. Intra-individual reference values will be determined in the peripheral blood (control values), drawn from existing intravenous access lines. Furthermore, results from molecular biology analyses will be compared to radiographical determined hematoma volume and neurological long term outcome. In addition, we will analyze other known predictors for neurological outcome after SAH. Primary endpoint is the expression of HO-1 in relation to the neurological long term outcome (modified Rankin disability scale, mRS). Secondary endpoints are HO-1 expression in relation to hematoma volume, neuroinflammation and in relation to other known predictors of poor neurological long term outcome (demography, medical history, laboratory values at admission, SAH-dependent variables: Hunt&Hess, Fisher, aneurysma localization, hydrocephalus, brain edema, intracerebral hemorrhage).
Hypothesis 1: Adequate central HO-1 induction (relation HO-1 in cerebrospinal fluid/HO-1 in peripheral blood) has a signifikant influence on neurological long term outcome (mRS).
Hypothesis 2: HO-1 expression in the cerebrospinal fluid shows a significant correlation with the hematoma volume.
Hypothesis 3: Adequate central HO-1 induction significantly influences the neuroinflammatory response.
Hypothesis 4: Adequate central HO-1 induction has an equal predictive value as other known predictors of neurological outcome after SAH.

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Organizational Data

  •   DRKS00008981
  •   2015/07/31
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  •   yes
  •   Approved
  •   293/15, Ethik-Kommission der Albert-Ludwigs-Universität Freiburg
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Secondary IDs

  •   U1111-1172-6077 
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Health Condition or Problem studied

  •   I60 -  Subarachnoid haemorrhage
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Interventions/Observational Groups

  •   In patients with subarachnoid hemorrhage we will obtain blood and cerebrospinal fluid samples from existing access tubes at different time points (day 1, day 7, day 14 after hemorrhage occurrence) to compare with diagnostic parameters obtained during treatment (CT-scans, laboratory parameters, clinical evaluation, neurological outcome by modified Rankin disability scale, mRS).
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Characteristics

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

HO-1 expression (real-time PCR) in relation to the neurological long term outcome (modified Rankin scale, mRS).

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Secondary Outcome

1. HO-1 expression in relation to hematoma volume (CT-scan)
2. HO-1 expression in relation to neuroinflammation (cytokine measurement in the cerebrospinal fluid)
3. HO-1 expression in relation to other known predictors of poor neurological long term outcome (demography, medical history, laboratory values at admission, SAH-dependent variables: Hunt&Hess, Fisher, aneurysma localization, hydrocephalus, brain edema, intracerebral hemorrhage).

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2015/09/01
  •   110
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

1. male and female patients >18 years of age.
2. confirmed diagnosis of SAH by diagnostic imaging or by cerebrospinal fluid analysis (lumbar puncture with blood/xanthochromia).
3. admission to the University Medical Center Freiburg with 24h after symptom onset.
4. therapeutical intervention with EVD/lumbar drain and central venous/arterial line placement.
5. ability to consent, either personal or by healthcare proxy.

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Exclusion Criteria

1. children <18 years of age.
2. admission later than 24h after symptom onset
3. patient deceases within 24h after admission.
4. radiographic evidence for additional subdural or epidurale hemorrhage.
5. radiographic evidence for meningitis or encephalitis.
6. pregnant patients
7. patients with sepsis, SIRS or other systemic inflammation states.
8. patients with pre-existing mental disabilities.

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Addresses

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    • Universitätsklinik Freiburg, Klinik für Anästhesiologie und Intensivmedizin
    • Mr.  Dr.  Nils  Schallner 
    • Hugstetter Str. 55
    • 79106  Freiburg
    • Germany
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    • Universitätsklinik Freiburg, Klinik für Neurologie
    • Mr.  Dr.  Wolf  Niesen 
    • Breisacher Str. 64
    • 79106  Freiburg
    • Germany
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    • Universitätsklinik Freiburg, Klinik für Neurochirurgie
    • Mr.  Dr.  Klaus-Jürgen  Butler 
    • Breisacher Str. 64
    • 79106  Freiburg
    • Germany
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    • Universitätsklinik Freiburg, Klinik für Anästhesiologie und Intensivmedizin
    • Mr.  Dr.  Nils  Schallner 
    • Hugstetter Str. 55
    • 79106  Freiburg
    • Germany
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    • Universitätsklinik Freiburg, Klinik für Anästhesiologie und Intensivmedizin
    • Mr.  Dr.  Nils  Schallner 
    • Hugstetter Str. 55
    • 79106  Freiburg
    • Germany
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Sources of Monetary or Material Support

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    • Deutsche Forschungsgemeinschaft e.V.
    • Kennedyallee 40
    • 53175  Bonn
    • 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.