Clinical trial NCT02722642: Autologous Bronchial Basal Cells Transplantation for Treatment of Bronchiectasis
Official title: A Single-center, Non-randomized, Before-and-after Self Control Study of Bronchial Basal Cell Transplantation for Bronchiectasis Treatment
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Bronchiectasis
Lead sponsor: Regend Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Southwest Hospital, China
name: Tongji University
First posted: 2016-03-30
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: CT imaging of dilated bronchi
timeFrame: 3 day - 6 months
Secondary outcomes:
measure: 6-minute walk distance test
timeFrame: 3 day - 6 months
measure: MRC chronic dyspnea scale
timeFrame: 3 day - 6 months
measure: St. George's Respiratory Questionnaire (SGRQ) scale
timeFrame: 3 day - 6 months
measure: inflammation indicators
timeFrame: 3 day - 6 months
measure: fibrotic factor level
timeFrame: 3 day - 6 months
measure: incidence of acute exacerbation
timeFrame: 3 day-6 months
measure: patients' self-evaluation
timeFrame: 3 day - 6 months
measure: blood gas level（PH）
timeFrame: 3 day - 6 months
measure: blood gas level（HCO3）
timeFrame: 3 day - 6 months
measure: blood gas level（PaCO2）
timeFrame: 3 day - 6 months
measure: blood gas level（PaO2）
timeFrame: 3 day - 6 months
measure: pulmonary function test (DLco)
timeFrame: 3 day - 6 months
measure: pulmonary function test (FEV1)
timeFrame: 3 day - 6 months
measure: pulmonary function test (FVC)
timeFrame: 3 day - 6 months
measure: pulmonary function test (MVV)
timeFrame: 3 day - 6 months
measure: pulmonary function test (MMEF)
timeFrame: 3 day - 6 months
Other outcomes:
Locations:
city: Chongqing
country: China
facility: First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
state: Chongqing
Study officials:
affiliation: Regend Therapeutics Co.Ltd
name: Wei Zuo, Ph.D.
role: STUDY_CHAIR
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.