Bronchiectasis
Conditions
Keywords
Bronchiectasis, Bronchial basal cells, Autologous transplantation
Brief summary
Bronchiectasis is a disease resulted from progressive destruction of bronchi with no effective drug for its treatment. In this study, we intends to carry out a randomized, single-blinded, controlled pilot clinical trial at 1/2 phase. During the process, autologous bronchial basal cells (BBCs) will be dissected from trial tissue via bronchoscopic brushing. Then the BBCs will be expanded and detected by quality control. In the following, qualified BBCs will be injected directly into the lesion by fiberoptic bronchoscopy after airway clearance. The investigators will evaluate the safety and effectiveness of the treatment by measuring a serial of indicators, including occurrence of adverse events, pulmonary function, 6 minute walk distance (6MWD), the distance-saturation product (DSP), St. George's Respiratory Questionnaire (SGRQ), FACED scoring, bronchiectasis severity index (BSI) , and high-resolution computed tomography (HRCT) at week 4, week 12, and week 24 after cell transplantation.
Interventions
BIOLOGICALBronchial basal cells (BBCs)
Airway epithelial cells were collected in patients of the cell treatment group by a disposable 2-mm brush in order to obtain BBCs. The obtained tissue were washed and enzymatically digested to form a single-cell suspension, which was then cultured under R-Clone system, a patented technique of Regend Therapeutics, Ltd.. For patients in the cell treatment group, on the basis of B-ACT therapy, they were also received autologous BBCs transplantation. Cell suspension was diluted with normal saline. Fibrotic bronchoscopy was guided into the lobular or segmental airways and cells were instilled into lobes.
PROCEDUREBronchoscopic airway clearance treatment （B-ACT）
The bronchoscopy was performed by board-certified respiratory physicians of Ruijin Hospital using a flexible fiber-optic bronchoscope. B-ACT therapy was performed on all patients in both groups according to the protocol. In brief, continuous suction was performed with the sputum aspirator from the trachea to the subsegmental during the entering of bronchoscope to remove the visible secretions from entire respiratory tract, and then operators used normal saline to collect lavage fluid (the volume various depending on the operator's judgement).
Sponsors
Regend Therapeutics
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
The opaque sealed envelope method was used to conceal the allocation sequence. Both patients and investigators, except for the bronchoscopy operators, remained masked to the treatment assignment for the duration of the study. Only the investigators who performed the bronchoscopy were unblinded. The non-blinded investigators should not disclose any blind information to other investigators, participants, care providers, or outcomes assessors.
Intervention model description
Eligibility patients were randomly assigned in a 1:1 ratio to receive either autologous cell transplantation therapy (cell treatment group) or bronchoscopic airway clearance treatment (B-ACT therapy, control group).
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects diagnosed as bronchiectasis. * Subjects with a DLCO \< 80% predicted value. * Subjects with stable condition for more than 2 weeks. * Subjects can do pulmonary function tests. * 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 positive serological tests for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or syphilis (HBV carriers and patients with stable chronic hepatitis B could be accepted if titers of HBV DNA \< 500 IU/mL or copies \< 1000 copies/mL; patients with curative hepatitis C were eligible if HCV RNA tests were negative). * Subjects with any malignancy. * Subjects with 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 with other serious diseases, such as poorly controlled 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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diffusing capacity of the lung for carbon monoxide (DLCO) | Week 4, 12, and 24 after treatment | An indicator of pulmonary function |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Forced vital capacity (FVC) | Week 4, 12, and 24 after treatment | An indicator for pulmonary function test to indicate the maximum amount of air a person can expel from the lungs after a maximum inhalation |
| The ratio of forced expiratory volume in the first one second to the forced vital capacity (FEV1/FVC) | Week 4, 12, and 24 after treatment | An indicator in pulmonary function test to represent the proportion of a person's vital capacity that they are able to expire in the first second of forced expiration to the full vital capacity |
| Maximum Mid Expiratory Flow (MMEF) | Week 4, 12, and 24 after treatment | An indicator in pulmonary function test to stand for maximal (mid-)expiratory flow and is the peak of expiratory flow as taken from the flow-volume curve and measured in liters per second |
| Maximum Voluntary Ventilation (MVV) | Week 4, 12, and 24 after treatment | An indicator in pulmonary function test to measure the maximum amount of air that can be inhaled and exhaled within one minute |
| 6 minute walk distance (6MWD) and distance saturation product (DSP) | Week 4, 12, and 24 after treatment | An indicator for heart and pulmonary function |
| Forced expiratory volume measured at the first second (FEV1) | Week 4, 12, and 24 after treatment | An indicator for pulmonary function test to assess airway obstruction |
| FACED scoring | Week 4, 12, and 24 after treatment | An assessment of severity tool, validated for people with non-cystic fibrosis bronchiectasis. F means FEV1, A means Age, C means Chronic colonization, E means Extension, D means Dyspnoea. |
| Bronchiectasis Severity Index (BSI) | Week 4, 12, and 24 after treatment | A combination of clinical, radiological and microbiological features to predict morbidity and mortality. |
| High resolution computed tomography (HR-CT) imaging of lung | Week 4, 12, and 24 after treatment | An indicator for analysis of dilated bronchi, HR-CT images of lung will be analyzed to indicate the pulmonary structure |
| Safety outcomes: adverse events | Through study completion, an average of 24 weeks | Any unexpected and unfavorable medical occurrence related to any medical intervention in the study |
| St. George's Respiratory Questionnaire (SGRQ) | Week 4, 12, and 24 after treatment | An indicator to measure health status (quality of life) in patients with diseases of airways obstruction |
Countries
China
Outcome results
None listed