Clinical trial NCT03655795: Autologous Transplantation of Bronchial Basal Cells for Treatment of COPD
Official title: Autologous Transplantation of Bronchial Basal Cells for Treatment of Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: COPD
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Regend Therapeutics
First posted: 2018-08-31
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Chronic Obstructive Pulmonary Disease (COPD) is a disease characterized by long-term poor airflow, resulting in chronic pulmonary heart disease, chronic respiratory failure or even death. Till now, the damaged pulmonary bronchus structures in COPD patients cannot be repaired by recent clinical methods so far. In this study, we intends to carry out a single-centered, non-randomized and self-controlled clinical trial at an early phase. During the process, autologous bronchial basal cells (BBCs) will be dissected from trial tissue from 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 lavage. After six-month observation, the investigators will evaluate the safety and effectiveness of the treatment by measuring a serial of indicators, including occurrence of adverse events, pulmonary function, the CT imaging, 6 minute walk distance (6MWD), St. George's Respiratory Questionnaire (SGRQ), modified medical research council (mMRC) dyspnea scale and COPD assessment test (CAT).


Eligibility criteria: Inclusion Criteria:

* Subjects aged between 40 to 75.
* Subjects diagnosed with COPD and meet the following standards: a.sustained airway obstruction; b.presence of persistent airflow limitation confirmed by post-bronchodilator FEV1\<70% predicted value and FEV1/FVC \< 0.7.
* Subjects with pulmonary emphysema confirmed by imaging evidence.
* Subjects with DLCO\<80% predicted value in pulmonary function test.
* 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 suffering from any of the following pulmonary diseases: asthma, active tuberculosis, pulmonary embolism, pneumothorax, pulmonary artery hypertension or interstitial lung disease.
* 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 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: 6 months -1 year
Secondary outcomes:
measure: Forced expiratory volume measured at the first second (FEV1)
timeFrame: 6 months -1 year
measure: Forced vital capacity (FVC)
timeFrame: 6 months -1 year
measure: The ratio of forced expiratory volume in the first one second to the forced vital capacity (FEV1/FVC)
timeFrame: 6 months -1 year
measure: Maximum Mid Expiratory Flow (MMF)
timeFrame: 6 months -1 year
measure: Maximum Voluntary Ventilation (MVV)
timeFrame: 6 months -1 year
measure: 6-minute-walk test (6MWT)
timeFrame: 6 months -1 year
measure: Imaging of lung structure by high resolution computed tomography (HR-CT)
timeFrame: 6 months -1 year
measure: Assess life quality affected by the respiratory problem by St. George's respiratory questionnaire (SGRQ) scale
timeFrame: 6 months -1 year
measure: Modified medical research council (mMRC) chronic dyspnea scale to evaluate the level of dyspnea
timeFrame: 6 months -1 year
measure: COPD Assessment Test (CAT)
timeFrame: 6 months -1 year
Other outcomes:
Locations:
Study officials:
affiliation: Ruijin Hospital
name: Yun Feng, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zuo W, Zhang T, Wu DZ, Guan SP, Liew AA, Yamamoto Y, Wang X, Lim SJ, Vincent M, Lessard M, Crum CP, Xian W, McKeon F. p63(+)Krt5(+) distal airway stem cells are essential for lung regeneration. Nature. 2015 Jan 29;517(7536):616-20. doi: 10.1038/nature13903. Epub 2014 Nov 12.
citation: Ma Q, Ma Y, Dai X, Ren T, Fu Y, Liu W, Han Y, Wu Y, Cheng Y, Zhang T, Zuo W. Regeneration of functional alveoli by adult human SOX9+ airway basal cell transplantation. Protein Cell. 2018 Mar;9(3):267-282. doi: 10.1007/s13238-018-0506-y. Epub 2018 Jan 17.