MUcociliary Clearance IN Stroke (MUCINS)

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.

Study Overview

• Status: Recruiting
• Conditions: Stroke, Ischemic
• Intervention / Treatment: 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.

• Study Type: Observational
• Enrollment (Anticipated): 24

Contacts and Locations

Study Locations

• Germany
  • Berlin-Mitte, Germany, 10117
    • Recruiting
    • NeuroCure Clinical Research Center (NCRC), Charité

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
control	Diagnostic test: bronchoscopy; Patients will undergo bronchoscopy to sample respiratory tissue in different heights in order to analyze mucociliary clearance
stroke	Diagnostic test: bronchoscopy; Patients will undergo bronchoscopy to sample respiratory tissue in different heights in order to analyze mucociliary clearance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mucociliary Clearance	- number of cilia (scanning electron microscopy)	at time of bronchoscopy (within 2 weeks after acute ischemic stroke)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurence of stroke-associated pneumonia	Pneumonia is defined according to the consensus recommendations (Smith et al., Stroke 2015)	7 days after stroke
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)
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)
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: University of Luebeck; NeuroCure Clinical Research Center, Charite, Berlin; University of Giessen; Department of Infectiology and Pneumonology, Charite, Berlin; Labor Berlin - Charité Vivantes GmbH

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 30, 2021
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: March 19, 2019
• First Submitted That Met QC Criteria: March 19, 2019
• First Posted (ACTUAL): March 21, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 25, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Bronchoscopy; Acute Ischemic Stroke
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: MUCINS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No