Clinical trial NCT03884166: MUcociliary Clearance IN Stroke
Official title: MUcociliary Clearance IN Stroke
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Stroke, Ischemic
Keywords: Acute Ischemic Stroke
Bronchoscopy
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: NeuroCure Clinical Research Center, Charite, Berlin
name: Department of Infectiology and Pneumonology, Charite, Berlin
name: University of Giessen
name: University of Luebeck
name: Labor Berlin - Charité Vivantes GmbH
First posted: 2019-03-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility 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

Primary outcomes:
measure: Mucociliary Clearance
timeFrame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
measure: Mucociliary Clearance
timeFrame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
Secondary outcomes:
measure: Occurence of stroke-associated pneumonia
timeFrame: 7 days after stroke
measure: Activity of autonomous nervous system
timeFrame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
measure: Activity of immune System - Concentration of cytokines
timeFrame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
measure: Activity of immune System - Concentration of inflammatory markers
timeFrame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
measure: Activity of immune System - Expression of HLA-DR
timeFrame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
measure: Structural changes in respiratory tissue (nasal, tracheal and bronchial) - Autophagy
timeFrame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
measure: Structural changes in respiratory tissue (nasal, tracheal and bronchial) - Apoptosis
timeFrame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
measure: Structural changes in respiratory tissue (nasal, tracheal and bronchial) - Increase of secretory cells
timeFrame: at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
Other outcomes:
Locations:
city: Berlin-Mitte
country: Germany
facility: NeuroCure Clinical Research Center (NCRC), Charité
Study officials:
affiliation: Charite University, Berlin, Germany
name: Andreas Meisel, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: