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MUcociliary Clearance IN Stroke (MUCINS)

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ClinicalTrials.gov Identifier: NCT03884166
Recruitment Status : Not yet recruiting
First Posted : March 21, 2019
Last Update Posted : April 18, 2019
Sponsor:
Collaborators:
NeuroCure Clinical Research Center, Charite, Berlin
Department of Infectiology and Pneumonology, Charite, Berlin
University of Giessen
University of Luebeck
Labor Berlin - Charité Vivantes GmbH
Information provided by (Responsible Party):
Andreas Meisel, Charite University, Berlin, Germany

Brief Summary:

Stroke patients frequently suffer from stroke associated pneumonia. Pathophysiologically speaking, dysphagia and central nervous system (CNS)-injury induced immunosuppression largely contribute to the risk for pneumonia. In mouse models for stroke, the self-cleaning mechanisms of the lung are also affected by stroke, possibly further contributing to this risk.

The investigators designed a pilot-study to examine the structural and functional integrity of the self-cleaning mechanisms of the lung in stroke patients.


Condition or disease Intervention/treatment
Stroke, Ischemic Diagnostic Test: bronchoscopy

Detailed Description:

Survival and functional outcome of stroke is strongly depending on the occurence of pneumonia (stroke-associated pneumonia, SAP). Early diagnose and treatment of SAP is paramount in the treatment of stroke patients. While dysphagia strongly contributes to its pathogenesis, recent years have also shown a strong risk-modulation by CNS injury induced immunosuppression, making stroke patients more susceptible to SAP. Additionally, murine models of stroke showed changes in mucociliary clearance as possible contributors to SAP. It remains unclear, whether structural integrity and mucociliary clearance of the respiratory epithel change in stroke patients, and whether these changes might contribute to the occurence of SAP.

Therefore, the investigators designed this exploratory observational pilot-study to examine the structural and functional integrity of respiratory epithel in severely affected stroke patients and correlate these findings to immune phenotyping and occurence of SAP. The investigators will conduct bronchoscopy in severely affected stroke patients to collect histological samples in order to evaluate multiple tissue predictors, as well as perform optical coherence tomography to examine ciliary kinetics in-vivo. The investigators will furthermore perform serum and plasma immune phenotyping, record occuring pneumonias and correlate these data in order to identify possible predictors of pneumonia.


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Study Type : Observational
Estimated Enrollment : 24 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: MUcociliary Clearance IN Stroke
Estimated Study Start Date : May 1, 2019
Estimated Primary Completion Date : May 31, 2020
Estimated Study Completion Date : November 30, 2020

Group/Cohort Intervention/treatment
stroke Diagnostic Test: bronchoscopy
Patients will undergo bronchoscopy to sample respiratory tissue in different heights in order to analyze mucociliary clearance

control Diagnostic Test: bronchoscopy
Patients will undergo bronchoscopy to sample respiratory tissue in different heights in order to analyze mucociliary clearance




Primary Outcome Measures :
  1. Mucociliary Clearance [ Time Frame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke) ]
    - number of cilia (scanning electron microscopy)

  2. Mucociliary Clearance [ Time Frame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke) ]
    - activity of cilia given as frequency (in-vivo optical coherence tomography)


Secondary Outcome Measures :
  1. Occurence of stroke-associated pneumonia [ Time Frame: 7 days after stroke ]
    Pneumonia is defined according to the consensus recommendations (Smith et al., Stroke 2015)

  2. Activity of autonomous nervous system [ Time Frame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke) ]
    Concentration of Cortisol, Adrenaline and Noradrenaline in blood and heart frequency variability

  3. Activity of immune System - Concentration of cytokines [ Time Frame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke) ]
    Concentration of cytokines (IL-6, IL-13 and more) in blood

  4. Activity of immune System - Concentration of inflammatory markers [ Time Frame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke) ]
    Concentration of inflammatory markers (PCT, CRP) in blood

  5. Activity of immune System - Expression of HLA-DR [ Time Frame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke) ]
    Expression of Human Leukocyte Antigens (HLA)-DR on monocytes in antigens/cell

  6. Structural changes in respiratory tissue (nasal, tracheal and bronchial) - Autophagy [ Time Frame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke) ]
    Intensity of fluorescence of Light chain (LC) 3b protein, Aurora A and Human enhancer of filamentation (HEF)1

  7. Structural changes in respiratory tissue (nasal, tracheal and bronchial) - Apoptosis [ Time Frame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke) ]
    Intensity of fluorescence of TUNEL

  8. Structural changes in respiratory tissue (nasal, tracheal and bronchial) - Increase of secretory cells [ Time Frame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke) ]
    Expression levels of surfactant protein, Muc5a, SPDEF, Foxa3



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
The population of the observational cohort consists of severely affected stroke patients, which require diagnostic or therapeutic bronchoscopy, from within out academic stroke center (mostly from the interdisciplinary neurological-neurosurgical intensive care unit). The control group will consist of neurologically healthy individuals presenting for standard bronchoscopy for any reason, i.e. diagnostic exclusion of malignoma. These will be recruited from an academic pneumologic center. Our center is located in the metropolitan area of Berlin. Due to the exploratory, "pilot" characteristics of this study, there will be no targeted inclusion in terms of age or gender, but we aim for a representative sample.
Criteria

Inclusion Criteria:

  • Age ≥18 years
  • Informed consent signed by patient or legal representatives
  • Acute ischemic stroke within the past 2 weeks (except the control group)
  • Indication for diagnostic or therapeutic bronchoscopy

Exclusion Criteria:

  • Confirmed lung malignancies or specific inflammations of the lungs
  • Pneumonia (only control group)
  • Autoimmune diseases of respiratory system (only control group)
  • Chronic inflammatory diseases of respiratory system (only control group)
  • chronic obstructive pulmonary disease (COPD) and spastic diseases of respiratory system (only control group)
  • Patients being committed to psychiatric institutions or prisons

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03884166


Contacts
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Contact: Andreas Meisel, Prof. Dr. med. +49 30 450 560026 andreas.meisel@charite.de
Contact: Benjamin Hotter, Dr. med. +49 30 450 639729 benjamin.hotter@charite.de

Locations
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Germany
NeuroCure Clinical Research Center (NCRC), Charité Not yet recruiting
Berlin-Mitte, Germany, 10117
Contact: Andreas Meisel, Prof. Dr. med.    +49 30 450 560026    andreas.meisel@charite.de   
Contact: Benjamin Hotter, Dr. med.    +49 30 450 639 729    benjamin.hotter@charite.de   
Sponsors and Collaborators
Charite University, Berlin, Germany
NeuroCure Clinical Research Center, Charite, Berlin
Department of Infectiology and Pneumonology, Charite, Berlin
University of Giessen
University of Luebeck
Labor Berlin - Charité Vivantes GmbH
Investigators
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Principal Investigator: Andreas Meisel, Prof. Dr. med. Charite University, Berlin, Germany

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Responsible Party: Andreas Meisel, Prof. Dr. med., Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT03884166     History of Changes
Other Study ID Numbers: MUCINS
First Posted: March 21, 2019    Key Record Dates
Last Update Posted: April 18, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Andreas Meisel, Charite University, Berlin, Germany:
Acute Ischemic Stroke
Bronchoscopy

Additional relevant MeSH terms:
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Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases