Autologous Bronchial Basal Cells Transplantation for Treatment of Bronchiectasis

Study Overview
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Brief Summary
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Bronchiectasis is a result of chronic inflammation compounded by an inability to clear mucoid secretions. Inflammation results in progressive destruction of the normal lung architecture, in particular the elastic fibers of bronchi. Currently there is no effective drug for bronchiectasis. This study intends to carry out an open, single-center, non-randomized, self control phase I/II clinical trial. During the treatment, bronchial basal cells (BCCs) will be isolated from patients' own bronchi by bronchoscopic brushing and expanded in vitro. Cultured cells will be injected directly into the lesion by fiberoptic bronchoscopy after lavage. After six-month observation, the investigators will evaluate the safety and effectiveness of the treatment by measuring the key indicator-- the CT imaging of dilated bronchi as well as four secondary indicators including the pulmonary function, laboratory factor level, incidence of acute exacerbation and the patients' self-evaluation.

Detailed Description
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Bronchiectasis is a term for irreversible lung damage resulting from recurrent episodes of infection and inflammation. Bronchial basal cells (BCCs) have been proven with stem cell activity to regenerate bronchi and repair lung damage. In this single-center, non-randomized, self control phase I/II clinical trial, patients' own BCCs will be grown in laboratory before injected to the damaged part of lung tissue. Transplanted BCCs have the potential to replenish the bronchial epithelium and reconstruct respiratory architecture.

Official Title
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A Single-center, Non-randomized, Before-and-after Self Control Study of Bronchial Basal Cell Transplantation for Bronchiectasis Treatment

Conditions
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Bronchiectasis

Intervention / Treatment
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* Biological: Bronchial basal cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects diagnosed as bronchiectasis. Subjects with at least 6 lung segments affected. Subjects with stable condition for more than 2 weeks. Subjects can tolerate bronchoscopy. Subjects signed informed consent. Exclusion Criteria: Women of childbearing age at the stage of pregnancy or lactation, or those without taking effective contraceptive measures. Subjects with syphilis or HIV positive antibody. Subjects with any malignancy. Subjects suffering from any of the following pulmonary diseases: active tuberculosis, pulmonary embolism, pneumothorax, multiple huge bullae, uncontrolled asthma, acute exacerbation of chronic bronchitis or extremely severe COPD. 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 the upper limit of normal. Subjects with liver disease or liver damage: ALT, AST, total bilirubin> 2 times 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 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bronchial basal cells<br>Patients will receive 10^6 (1 million)/Kg/person cells of clinical grade bronchial basal cells (BBCs) injected via fiberoptic bronchoscopy after fully lavage of the localized lesions. | Biological: Bronchial basal cells<br>* Patients will receive 10^6 (1 million) /Kg/person cells of clinical grade bronchial basal cells (BBCs) injected via fiberoptic bronchoscopy after fully lavage of the localized lesions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CT imaging of dilated bronchi | CT image of dilated bronchi will be analyzed.Clinical indicators include the spread of dilation, extent of dilation and the thickness of bronchi wall. | 3 day - 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-minute walk distance test |  | 3 day - 6 months | 
| MRC chronic dyspnea scale |  | 3 day - 6 months | 
| St. George's Respiratory Questionnaire (SGRQ) scale |  | 3 day - 6 months | 
| inflammation indicators | TNF-α,IL1-β,PDGF,MMP9,TIMP1,CRP, PCT | 3 day - 6 months | 
| fibrotic factor level | TGF-β, Hydroxyproline | 3 day - 6 months | 
| incidence of acute exacerbation |  | 3 day-6 months | 
| patients' self-evaluation | The self-efficacy evaluation can also be classified into four levels: effective, improved, stable and invalid. | 3 day - 6 months | 
| blood gas level（PH） |  | 3 day - 6 months | 
| blood gas level（HCO3） |  | 3 day - 6 months | 
| blood gas level（PaCO2） |  | 3 day - 6 months | 
| blood gas level（PaO2） |  | 3 day - 6 months | 
| pulmonary function test (DLco) | Diffusing capacity of CO | 3 day - 6 months | 
| pulmonary function test (FEV1) | Forced expiratory volume in one second, FEV1 | 3 day - 6 months | 
| pulmonary function test (FVC) | forced vital capacity | 3 day - 6 months | 
| pulmonary function test (MVV) | maximal voluntary ventilation | 3 day - 6 months | 
| pulmonary function test (MMEF) | maximal midexpiratory flow curve | 3 day - 6 months |