Clinical trial NCT05594303: COPD Treatment by Transplantation of Autologous Bronchial Basal Cells
Official title: Research on Chronic Obstructive Pulmonary Disease (COPD) Treatment by Transplantation of Autologous Bronchial Basal Cells
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: COPD
cell therapy
bronchial basal cells
autologous transplantation
Lead sponsor: Guangzhou Institute of Respiratory Disease
Sponsor class: OTHER
Collaborators: name: Regend Therapeutics
First posted: 2022-10-26
Enrollment: 6
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Chronic obstructive pulmonary disease (COPD) is a group of disease characterized by obstructed airflow. Usually, the lung structure is gradually impaired along with the progression of the disease. Recently, the treatment of disease is challenged by shortage of approaches for regenerating the injured lung tissue. Here in this study, investigators intend to perform a single-centered, open, concurrent-controlled phase I/II clinical trial with autologous bronchial basal cells on COPD treatment since they were proved to regenerate lung tissue in animal models. The participants is recruited and divided into experiment group and control group. For patients from experiment group, bronchial basal cells will be isolated, expanded, carefully characterized in vitro and transplanted autologously into lung by fiberoptic bronchoscopy. No intervention is performed for patients from control group. During the study, the safety and efficacy will be evaluated on all the subjects by measuring the key indicators.


Eligibility criteria: Inclusion Criteria:

* Subjects aged between 40 to 75;
* Subjects diagnosed with COPD and meet the following standards: a. sustained airway obstruction; b. post-bronchodilator FEV1\<80% predicted value;
* Subjects with DLCO\<80% predicted value in spirometry;
* Subjects with a smoking history more than 10 pack-years (current smoker and former smoker);
* Subjects with stable condition for more than 4 weeks;
* Subjects tolerant to bronchoscopy;
* Subjects signed informed consent.

Exclusion Criteria:

* Pregnant or lactating women;
* Subjects with syphilis or any of HIV, HBV, HCV positive antibody;
* Subjects with any malignancy;
* Subjects requiring anti-infection (bacteria or virus) treatment by intravenous drugs;
* Subjects suffering from any of the following pulmonary diseases: asthma, active tuberculosis, pulmonary embolism, pneumothorax, pulmonary artery hypertension caused by other diseases;
* Subjects with a history of invasive or non-invasive mechanical ventilation in the past 4 weeks;
* Subjects suffering from other serious diseases, such as diabetes, myocardial infarction, unstable angina, cirrhosis, and acute glomerulonephritis;
* Subjects with leukopenia (WBC less than 4x10\^9 / L) or agranulocytosis (WBC less than 1.5x10\^9 / L or neutrophils less than 0.5x10\^9 / L) caused by any reason;
* Subjects with severe renal impairment, serum creatinine\> 1.5 times of the upper limit of normal;
* Subjects with liver disease or liver damage: ALT, AST, total bilirubin\> 2 times of the upper limit of normal;
* Subjects with a history of mental illness or suicide risk, with a history of epilepsy or other central nervous system disorders;
* Subjects with severe arrhythmias (such as ventricular tachycardia, frequent superventricular tachycardia, atrial fibrillation, and atrial flutter, etc.) or cardiac degree II or above conduction abnormalities displayed via 12-lead ECG;
* Subjects with a history of alcohol or illicit drug abuse;
* Subjects allergic to products from cattle and pig;
* Subjects accepted by any other clinical trials within 3 months before the enrollment;
* Subjects with poor compliance, difficult to complete the study;
* Any other conditions that might increase the risk of subjects or interfere with the clinical trial.

Primary outcomes:
measure: Diffusing capacity of the lung for carbon monoxide (DLCO)
timeFrame: Change from baseline DLCO at 3 months after transplantation
Secondary outcomes:
measure: Forced expiratory volume in one second (FEV1)
timeFrame: Before transplantation, 3 months after transplantation, 6 months after transplantation and a year after transplantation
measure: Forced vital capacity (FVC)
timeFrame: Before transplantation, 3 months after transplantation, 6 months after transplantation and a year after transplantation
measure: The ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC)
timeFrame: Before transplantation, 3 months after transplantation, 6 months after transplantation and a year after transplantation
measure: Maximum voluntary ventilation (MVV)
timeFrame: Before transplantation, 3 months after transplantation, 6 months after transplantation and a year after transplantation
measure: 6-minute-walk test (6MWT)
timeFrame: Before transplantation, 3 months after transplantation, 6 months after transplantation and a year after transplantation
measure: Imaging of lung structure by computed tomography (CT)
timeFrame: Before transplantation, 3 months after transplantation, 6 months after transplantation and a year after transplantation
measure: Assess life quality affected by the respiratory problem by St. George's respiratory questionnaire (SGRQ) scale
timeFrame: Before transplantation, 3 months after transplantation, 6 months after transplantation and a year after transplantation
measure: Chronic obstructive pulmonary disease assessment test (CAT)
timeFrame: Before transplantation, 3 months after transplantation, 6 months after transplantation and a year after transplantation
measure: Diffusing capacity of the lung for carbon monoxide (DLCO)
timeFrame: Change from baseline DLCO at 6 months after transplantation
measure: Diffusing capacity of the lung for carbon monoxide (DLCO)
timeFrame: Change from baseline DLCO at 12 months after transplantation
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University
name: Shiyue Li
role: PRINCIPAL_INVESTIGATOR
References: