UMIN-CTR Clinical Trial

Public title

Elucidation of the pathogenesis of chronic lower respiratory tract infection focusing on the phagocytic ability of lung macrophage phenotypes and the bacterial flora of the lower airway

Acronym

Elucidation of the pathogenesis of chronic lower respiratory tract infection focusing on the phagocytic ability of lung macrophage phenotypes and the bacterial flora of the lower airway

Scientific Title

Elucidation of the pathogenesis of chronic lower respiratory tract infection focusing on the phagocytic ability of lung macrophage phenotypes and the bacterial flora of the lower airway

Scientific Title:Acronym

Elucidation of the pathogenesis of chronic lower respiratory tract infection focusing on the phagocytic ability of lung macrophage phenotypes and the bacterial flora of the lower airway

Region

Japan

Condition

chronic lower respiratory tract infection

Classification by specialty

Medicine in general	Pneumology	Infectious disease

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The aim of this study is to evaluate the role of bacterial flora that are detected by cultivation-independent molecular biological modalities using bronchoalveolar lavage fluid (BALF). BALF specimens were directly obtained from lung lesion of patient with chronic lower respiratory tract infection or pulmonary nontuberculous mycobacteriosis(NTM). In addition, we use flow cytometry to isolate the alveolar macrophages from the BALF and quantify the phagocytic ability of macrophages against bacteria and fungi. We then simultaneously compare the results of the flow cytometry, a bacterial flora analysis, imaging findings of the airway/lung lesions of patients with pulmonary NTM, timing of illness progression, prognosis, disease duration and the relationship with antibiotic therapy. Based on the results of this study, our goal is to establish new therapeutic strategies such as the use of antimycotics and antifungal drugs from the early stage of this disease.

Basic objectives2

Others

Basic objectives -Others

We compare patients with and without pulmonary NTM disease and evaluate the statistically significant differences in the results of the bacterial flora analysis, the differentiation ability according to the macrophages phenotypes (proportion of macrophages phenotype), and the CT findings.

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

We compare patients with and without pulmonary NTM disease and evaluate the statistically significant differences in the results of the bacterial flora analysis, the differentiation ability according to the macrophages phenotypes (proportion of macrophages phenotype), and the CT findings.

Key secondary outcomes

We evaluate the following problems at the start of the test and 24 to 28 weeks after this trial started.
1) Clinical manifestations, laboratory findings
2) Microbiological evaluation:
Transition of causative bacteria with sputum
3) Cytokines, oxidative stress markers in BALF (including TNF-a, NOS, HO-1, IL-4, IL-6, IL-8, IL-13 and others).
4) The time-dependent change of the CT findings

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Patients with suspected chronic lower respiratory tract infection (including pulmonary NTM disease) and who meet the following selection criteria and do not conflict with the exclusion criteria are registered.

We use the microbiological criteria for the American Thoracic Society/Infectious Disease Society of America definition of NTM with a few modifications. A diagnosis of NTM required the fulfilment of the following radiographic criteria and at least one of the following microbiologic criteria.

A. Radiographic criteria
1. Chest imaging findings showing either nodular shadow, small nodular shadow, branched shadow, uniformity shadow, cavity opacities, or multifocal bronchiectasis findings
2. Exclusion of other diagnoses

B. Microbiologic criteria
1. Positive culture results for at least two separate expectorated sputum samples
2. Positive culture results for one bronchial wash/lavage sample
3. Positive findings on a transbronchial or other lung biopsy with histopathological features of mycobacteria, and one or more sputum or bronchial washing cultures positive for NTM

Key exclusion criteria

The following patients are excluded.
1. Patients who do not agree with this study
2. Patients for whom bronchoscopy is difficult to preform because of comorbidity and who do not agree with bronchoscopy

Target sample size

50

Name of lead principal investigator

1st name	Kei
Middle name
Last name	Yamasaki

Organization

University of Occupational and Environmental Health, Japan

Division name

Department of Respiratory Medicine

Zip code

807-8555

Address

1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu city, Fukuoka, 807-8555, Japan

TEL

093-691-7453

Email

yamasaki@med.uoeh-u.ac.jp

Name of contact person

1st name	Hiroaki
Middle name
Last name	Ikegami

Organization

University of Occupational and Environmental Health, Japan

Division name

Department of Respiratory Medicine

Zip code

807-8555

Address

1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu city, Fukuoka, 807-8555, Japan

TEL

093-691-7453

Homepage URL

Email

h_i214538y@yahoo.co.jp

Institute

Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Ethics Committee of Medical Research,University of Occupational and Environmental Health,Japan

Address

1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu city, Fukuoka, 807-8555, Japan

Tel

093-691-7205

Email

daigakukanri@mbox.pub.uoeh-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2018

Year

09

Month

03

Day

URL releasing protocol

https://www.sciencedirect.com/science/article/pii/S1341321X22002148?via%3Dihub

Publication of results

Published

URL related to results and publications

https://www.sciencedirect.com/science/article/pii/S1341321X22002148?via%3Dihub

Number of participants that the trial has enrolled

30

Results

This study revealed that AMs of the patients with NTM infection accounted for a higher rate of non-polarized (HLA-DR+CD40-CD163-) macrophage than that in the controls. In addition, AMs in the NTM group had an impaired ability to phagocytose S. aureus. In vitro experiments revealed increased intracellular S. aureus counts in M. intracellulare-infected macrophages compared with those in non-NTM-infected macrophages.

Results date posted

2022

Year

09

Month

16

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

11 NTM-infected and 19 non-NTM-infected patients participated in the study. There were no patients with COPD in either group. Among the patients with NTM infection, the detected NTM were M. avium (n = 6) and M. intracellulare (n = 5). There were no significant differences in clinical characteristics between NTM- and non-NTM-infected patients.

Participant flow

The clinical data collected from the participants included age, gender, comorbid diseases, and medications. Then, they underwent bronchoscopy for diagnostic purposes of pulmonary NTM disease.

Adverse events

There were no adverse events associated with bronchoscopy.

Outcome measures

BALF was evaluated to differentiate AM phenotypes (CD40: M1 marker, CD163: M2 marker, MHC class II: macrophage marker), and their phagocytosis was examined. In vitro study, macrophage cell lines infected with Mycobacterium intracellulare were co-infected with Staphylococcus aureus to evaluate the bactericidal ability.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2018

Year

08

Month

01

Day

Date of IRB

2018

Year

10

Month

10

Day

Anticipated trial start date

2018

Year

10

Month

11

Day

Last follow-up date

2021

Year

06

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

This clinical trial is a prospective observational study. Patients who meet selection criteria and do not conflict with exclusion criteria are included.
This study is scheduled to end in June 2021.

Registered date

2018

Year

09

Month

02

Day

Last modified on

2022

Year

09

Month

16

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000038765