Activation of Apoptosis-related Receptors on Alveolar Macrophages

NCT04775394 | Completed

• 1 other identifier: 20-04 ROBAL
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The aim is to understand whether activation of receptors involved in clearance of apoptotic cells will improve efferocytosis in COPD patients in vitro and whether generation of pro-inflammatory cytokines can be decreased in COPD patients.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• Percentage of pH-Rhodo-positive alveolar macrophages

  Research compounds will be tested for the ability to influence the amount of efferocytosis against apoptotic cells, measuring the relative numbers of isolated alveolar macrophages that performed efferocytosis using flow cytometry.

  Ex-vivo, after collection of bronchoalveolar lavage (BAL) on Day 1

Study Arms (2)

Pilot Part: Healthy subjects

EXPERIMENTAL

3-5 healthy ex-smokers with normal lung function to establish methods

Other: Bronchoscopy

Main Part: COPD patients and Healthy Controls

EXPERIMENTAL

8 subjects with COPD stage II and III who are ex-smokers and have a history of chronic cough and sputum production and 5-8 healthy, age-matched controls

Other: Bronchoscopy

Interventions

Bronchoscopy OTHER

Bronchoalveolar lavage, mucosal biopsy and bronchial brushes during bronchoscopy

Main Part: COPD patients and Healthy Controls; Pilot Part: Healthy subjects

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy volunteers
• Able and willing to give written informed consent.
• Normal lung function with Forced Expiratory Volume in 1 second (FEV1) predicted ≥ 80% and FEV1/Forced Vital Capacity (FVC) \> 70%.
• Body mass index between 18 and 32 kg/m2
• Ex-smokers since at least 12 months with a smoking history of at least 10 pack years.
• Able and willing to give written informed consent
• COPD subjects
• Clinical diagnosis of COPD stage II and III
• History of chronic cough and sputum production
• FEV1/FVC \<70% post-bronchodilator at visit 1
• FEV1 30-80% of the predicted normal value post-bronchodilator at visit 1
• FEV1 \>1.5 L
• Absence of lung emphysema assessed by pulmonary function measurement at visit 1: Total Lung Capacity (TLC) \<120% of predicted normal, Residual Volume (RV) \<120% of predicted normal, Diffusing Capacity for Carbon Monoxide (DLCO) \>80%
• Ex-smokers since at least 12 months with a smoking history of at least 10 pack years.
• Body mass index between 18 and 32 kg/m2.

You may not qualify if:

• Healthy volunteers
• Past or present disease, which as judged by the investigator, may affect the outcome of the study or put the subject at risk because of participation in the study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease, psychiatric disease, endocrine disease, infectious disease, inflammatory disease or pulmonary disease (including but not confined to asthma, tuberculosis, bronchiectasis or cystic fibrosis)
• Regular intake of any prescribed or over the counter medication. Exceptions include paracetamol for pain relief, oral contraceptive medication, hormonal replacement therapy, dietary and vitamin supplements
• Clinically relevant history of allergy as judged by the investigator
• Intolerance against standard medication used during bronchoscopy, e.g. lidocaine, midazolam.
• Infections of the lower respiratory tract within 6 weeks prior to screening
• Infections of the upper respiratory tract within 2 weeks prior to screening
• Any clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, urinalysis, vital signs, lung function, or ECG at Visit 1, which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or may influence the results of the study.
• HIV (Type I + Type II), hepatitis B or C, tuberculosis, or Sars-CoV-2 positive or not performed at visit 1
• Positive drug screen for methadone, cannabis, opiates, cocaine metabolites, amphetamines, barbiturates and benzodiazepines at visit 1
• History of drug or alcohol abuse
• Risk of non-compliance with study procedures
• Suspected inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study
• COPD subjects
• Past or present disease other than COPD, which as judged by the investigator, may affect the outcome of the study or put the subject at risk because of participation in the study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease, psychiatric disease, endocrine disease, infectious disease, inflammatory disease or pulmonary disease (including but not confined to asthma, tuberculosis, bronchiectasis or cystic fibrosis).

Sponsors & Collaborators

• Prof. Dr. Jens Hohlfeld: lead

Study Sites (1)

Fraunhofer ITEM

Hanover, Lower Saxony, 30625, Germany

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Bronchoscopy

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures

Study Officials

• Jens M Hohlfeld, Prof. Dr.

  Fraunhofer ITEM Hannover, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med. Jens M. Hohlfeld

Model Details: Enrolment will healthy subjects first, followed by subjects with COPD

Study Record Dates

• First Submitted: February 15, 2021
• First Posted: March 1, 2021
• Study Start: January 1, 2021
• Primary Completion: July 21, 2023
• Study Completion: July 21, 2023
• Last Updated: August 1, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)