MUcociliary Clearance IN Stroke

Stroke, Ischemic Clinical Trial

— MUCINS  

Official title:

MUcociliary Clearance IN Stroke

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03884166
• Other study ID #: MUCINS
• Status: Recruiting
• Start date: June 30, 2021
• Est. completion date: December 31, 2022

Study information

• Verified date: March 2022
• Source: Charite University, Berlin, Germany
• Contact: Andreas Meisel, Prof. Dr. med.
• Phone: +49 30 450 560026
• Email: andreas.meisel[@]charite.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 31, 2022
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ischemic Stroke
• Stroke
• Stroke, Ischemic

Intervention

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

Locations

Country	Name	City	State
Germany	NeuroCure Clinical Research Center (NCRC), Charité	Berlin-Mitte

Sponsors (6)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Department of Infectiology and Pneumonology, Charite, Berlin, Labor Berlin - Charité Vivantes GmbH, NeuroCure Clinical Research Center, Charite, Berlin, University of Giessen, University of Luebeck

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mucociliary Clearance	- number of cilia (scanning electron microscopy)	at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
Primary	Mucociliary Clearance	- activity of cilia given as frequency (in-vivo optical coherence tomography)	at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
Secondary	Occurence of stroke-associated pneumonia	Pneumonia is defined according to the consensus recommendations (Smith et al., Stroke 2015)	7 days after stroke
Secondary	Activity of autonomous nervous system	Concentration of Cortisol, Adrenaline and Noradrenaline in blood and heart frequency variability	at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
Secondary	Activity of immune System - Concentration of cytokines	Concentration of cytokines (IL-6, IL-13 and more) in blood	at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
Secondary	Activity of immune System - Concentration of inflammatory markers	Concentration of inflammatory markers (PCT, CRP) in blood	at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
Secondary	Activity of immune System - Expression of HLA-DR	Expression of Human Leukocyte Antigens (HLA)-DR on monocytes in antigens/cell	at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
Secondary	Structural changes in respiratory tissue (nasal, tracheal and bronchial) - Autophagy	Intensity of fluorescence of Light chain (LC) 3b protein, Aurora A and Human enhancer of filamentation (HEF)1	at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
Secondary	Structural changes in respiratory tissue (nasal, tracheal and bronchial) - Apoptosis	Intensity of fluorescence of TUNEL	at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
Secondary	Structural changes in respiratory tissue (nasal, tracheal and bronchial) - Increase of secretory cells	Expression levels of surfactant protein, Muc5a, SPDEF, Foxa3	at time of bronchoscopy (within 2 weeks after acute ischemic stroke)