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Cohort Study of Airway Microecology and the Pathogenesis and Evolution of Chronic Obstructive Pulmonary Disease

Sponsor
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University (Other)
Overall Status
Recruiting
CT.gov ID
NCT04849104
Collaborator
(none)
210
Enrollment
1
Location
58.1
Anticipated Duration (Months)
3.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will last for 5 years (2021.2.25-2025.12.31). 210 patients (70 cases in each group) will be enrolled in this study. Eight centers in China will participate in the study. The patients will be treated with bronchoscopy alveolar lavage, and 60 ml of bronchoalveolar lavage fluid will be collected for the next-generation sequencing of airway microorganisms. The patients will be followed up for 4 years to observe the changes of lung function, Fractional exhaled nitric oxide (FENO) and clinical symptoms.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    1. Research purposes:

    The main purpose: to detect the relationship between the changes in the airway microecology and the activation of macrophages, as well as the progression and heterogeneity of the early disease of COPD in patients with early COPD.

    The basis of the question:

    The current study found that the number of patients with COPD in my country is close to 100 million, and the number of deaths due to COPD every year ranks third among the deaths of each single disease in my country. However, the research on the pathogenesis of COPD has been slow and there is still no breakthrough. The results of research have brought innovations to the treatment of chronic obstructive pulmonary disease. The study found that the airway microecology has undergone significant changes in patients with moderate to severe COPD, but whether the airway microecology changes in the early COPD? If it changes, the airway microecology changes slowly in the early stage. What is the role in the evolution of obstructive lung disease? There is no relevant research report. This study intends to collect bronchoalveolar lavage fluid to detect the airway microecology and the activation of macrophages, and observe the changes in the airway microecology and the activation of macrophages in early COPD patients, as well as the early COPD Correlation between disease progression and heterogeneity.

    1. Research design:

    Planned number of cases: 70 cases of COPD high-risk patients/early COPD/mild-moderate COPD patients, a total of 210 cases. The main center plans to enroll 28 cases, each sub-center plans to enroll 26 cases, and each center enters the group competitively.

    1. Clinical trial process:

    3.1 Sign informed consent and collect relevant clinical data; for patients who are clearly diagnosed as COPD, the treatment plan formulated in the "Global Initiative for the Diagnosis, Treatment and Prevention of COPD" (the 2021 version of the GOLD Guidelines) Carry out standardized treatment.

    3.2 Under local anesthesia, perform bronchoalveolar lavage and recover bronchoalveolar lavage fluid;

    3.3 The recovered bronchoalveolar lavage fluid is divided into two parts. One part uses 16SrRNA high-throughput sequencing to detect the characteristics of the airway microecological composition of early COPD patients, and analyze the heterogeneity of the microecological composition of individual samples of early COPD patients. The other part of the specimen was centrifuged to separate the bronchoalveolar lavage fluid supernatant and cells.

    3.4 The cells in the bronchoalveolar lavage fluid were separated from macrophages by differential adhesion method, and M1 (CD68+CD80+CD86+CD163-CD206-) and M2 (CD68+CD80-CD86-) were detected by flow cytometry. CD163+CD206+) ratio; 3.5 The above-mentioned patients and healthy volunteers were followed up for 4 times in 4 years, and the changes in relevant clinical data were recorded. Primary endpoint: changes in lung function in high-risk patients with COPD/early COPD and mild-to-moderate COPD within 48 months; secondary endpoint: patients with high-risk COPD/early COPD patients and mild Changes in clinical symptoms in patients with moderate chronic obstructive pulmonary disease within 48 months. Analyze the correlation between airway microecological changes, the heterogeneity of microecological composition ratio, macrophage activation and the disease progression and heterogeneity of early COPD patients.

    (Remarks: If the subject has an acute exacerbation of chronic obstructive pulmonary disease at the time of follow-up, he will be treated according to the diagnosis and treatment standards, and the visit task at this node will be completed after the acute exacerbation is relieved for 1 month. )

    1. quality assurance of clinical trial data

    The quality control of this clinical trial is under the control and control of the 9th People's Hospital Affiliated to the Medical College of Shanghai Jiaotong University. The research work is carried out in accordance with GCP, SOP and quality control requirements, the clinical research plan is formulated, and GCP training is conducted for the relevant researchers participating in the test.

    4.1 The plan before the trial is started shall be submitted to the ethics committee of the Ninth People's Hospital Affiliated to the Medical College of Shanghai Jiaotong University for approval;

    4.2 According to the GCP guidelines, necessary steps should be taken in the design and implementation stage of the study to ensure the accuracy, consistency, integrity and credibility of the collected data;

    4.3 The participants will conduct the test in strict accordance with the GCP standard in China, collect and record the contents in the case report form truthfully, carefully and in detail according to the SOP of clinical trial standard, and verify the contents to ensure the reliability of the data;

    4.4 The researchers fill in the information required by the program into the case report form (CRF), and the supervisor will verify that the information is complete and accurate, and guide the staff of the research center to make necessary corrections and supplements;

    4.5 All instruments, equipment, reagents, standard products, etc. used in various inspection items in clinical trials shall have strict quality standards and ensure that they work under normal conditions;

    4.6 The statistical problems in the test plan shall be submitted to the statistical experts for examination and verification;

    4.7 During the trial, researchers monitored the research process, informed consent, the correctness and completeness of data in case report form (CRF).

    1. record, preservation, sharing agreement and declaration of conflict of interest of research materials

    According to GCP principle, the researcher shall keep all the detailed original documents of the subjects, and record the contents of the test process, drug use, laboratory examination data, safety data and efficacy evaluation in the case report form. The recorded data shall be complete, timely and clear. The case report form, original documents, medical records, etc. shall be clear, detailed and easily recognized by the personnel participating in this clinical trial.

    The key investigator must sign at least the selected confirmation page and completion page of the case report form to verify the accuracy and integrity of all data.

    The case report form and original documents can only be modified by the investigator. No modification to the case report form and original document shall be allowed to smear out the original data. The correct method of modification is to mark single line on the original data, then write the modified data next to the original data, and sign the date and the abbreviation of the modified personnel.

    The test data shall be kept for 10 years after the end of the test. However, if required by the current regulations or in agreements with the sponsor, the information should be kept for a longer period of time.

    The research results are shared by the contribution ranking of each center. There is no conflict of interest in each research center.

    1. statistical treatment scheme

    6.1 filling in the case report form (CRF) The investigator should complete the filling of case report form in time, modify it according to the correct modification method, and the completed case report form shall be reviewed and signed by the main researchers.

    6.2 statistical analysis method and statistical description

    6.2.1 Treatment of missing value of main efficacy index data: when some subjects lack a major efficacy data, the method of filling deficiency is determined from the statistical and professional perspective. If the case is missing, the data of the previous measurement shall be transferred.

    6.2.2 Case analysis of incomplete test: the reasons for exfoliation should be analyzed one by one.

    6.2.3 Descriptive statistics: mean, standard deviation, maximum value, minimum value, median, confidence interval, frequency (composition ratio), etc.

    6.3 Statistical expression

    6.3.1 The report mainly uses tables to show that the tables are self-evident, that is, they have table questions, table notes and examples.

    6.3.2 The results of repeated measurement data are expressed in tables and statistical charts are attached to increase readability.

    6.4 statistical software

    SAS 9.1.3 and Das for clinical trial 3.0 software were used to analyze the software simultaneously, and the results were confirmed.

    1. modification and interim analysis in the course of the test

    Once the research plan has been discussed by the research group and reviewed by the ethics committee, it is not allowed to change at will; before the modification is implemented, the researcher must report the content and reason of the modification to the ethics committee of clinical trial for approval, and then carry out the research according to the modified scheme.

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    210 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Cohort Study of Airway Microecology and the Pathogenesis and Evolution of Chronic Obstructive Pulmonary Disease
    Actual Study Start Date :
    Feb 26, 2021
    Anticipated Primary Completion Date :
    Dec 31, 2025
    Anticipated Study Completion Date :
    Dec 31, 2025

    Arms and Interventions

    Arm Intervention/Treatment
    COPD high-risk patients

    age <60 years old, long-term smoker (≥10 pack years), CT without macroscopic airway abnormalities and/or mild or moderate emphysema, air retention or bronchial thickening, normal lung function
    Early-stage COPD patients

    those who are younger than 60 years old, long-term smokers (≥10 pack years) and have any of the following abnormalities: Forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) <lower limit of normal value (LLN, 80%); CT abnormalities: abnormal airway and/or emphysema, air retention or bronchial wall thickening; FEV1 drops rapidly (≥60 mL/year);
    patients with mild to moderate COPD

    Patients with mild to moderate COPD: age <65 years, FEV1/FVC<70%, FEV1 predicted value ≥50%

    Outcome Measures

    Primary Outcome Measures

    1. Forced vital capacity(FVC) [0， 12，24，36，48months]

      The change of FVC at each time node

    2. Forced expiratory volume in the first second(FEV1) [0， 12，24，36，48months]

      The change of FEV1 at each time node

    3. Forced expiratory rate in the first second (FEV1%=FEV1/FVC) [0， 12，24，36，48months]

      The change of FEV1% at each time node

    4. Exhaled nitric oxide (FENO) [0， 12，24，36，48months]

      The change of FENO at each time node

    Secondary Outcome Measures

    1. breathlessness measurement using the modified British Medical Research Council (mMRC) [0， 12， 24， 36， 48months]

      The change of mMRC at each time node

    2. COPD assessment test (CAT) [0， 12， 24， 36， 48months]

      The change of CAT at each time node

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Have the ability to communicate orally or in writing and sign an informed consent form;

    2. Age from 18 to 60 years (the age of patients with mild to moderate COPD <65 years), regardless of gender;

    3. Meet the above-mentioned early diagnosis criteria for high-risk patients with COPD/early-stage COPD/mild to moderate COPD.

    Exclusion Criteria:

    1. Patients suffering from any of the following diseases: active tuberculosis, severe bronchiectasis, lung abscess, aspiration pneumonia, lung tumor, non-infectious interstitial lung disease, pulmonary edema, atelectasis, pneumothorax, pleural effusion , Pulmonary embolism, pulmonary eosinophilic infiltration, and pulmonary vasculitis;

    2. Patients with a history of tumors or patients with current tumors;

    3. The patient has severe renal impairment: creatinine clearance rate <30ml/min/1.73m2 or serum creatinine>265μmol/L (>3mg/dL);

    4. Patients suffering from liver disease or severe liver damage: ALT, AST> 2 times the upper limit of normal;

    5. pregnancy;

    6. Severe COPD, FEV1 predicted value ≤50%;

    7. Severe heart disease, such as coronary heart disease, heart failure, etc.;

    8. Severe coagulopathy: INR>1.4, PTT>40s, PLT<150x103 cells

    9. Bronchial Asthma;

    10. Severe alcoholism;

    11. diabetes;

    12. Have used antibiotics within two months,

    13. Used systemic and local hormones;

    14. Cannot sign the informed consent form;

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University Shanghai Shanghai China 200011

    Sponsors and Collaborators

    • Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

    Investigators

    • Study Chair: Weining Xiong, doctor, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
    ClinicalTrials.gov Identifier:
    NCT04849104
    Other Study ID Numbers:
    • COPD-BALF2021
    First Posted:
    Apr 19, 2021
    Last Update Posted:
    Apr 19, 2021
    Last Verified:
    Jan 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
    chronic obstructive pulmonary disease
    Additional relevant MeSH terms:
    Lung Diseases
    Lung Diseases, Obstructive
    Pulmonary Disease, Chronic Obstructive

    Study Results

    No Results Posted as of Apr 19, 2021