Autologous Bronchial Basal Cells Transplantation for Treatment of Bronchiectasis

Bronchiectasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02722642
• Other study ID #: 201602301
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 2016
• Est. completion date: June 2020

Study information

• Verified date: March 2020
• Source: Regend Therapeutics
• Contact: Wei Zuo, Ph.D.
• Phone: +86-21-65985082
• Email: zuow[@]regend.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: June 2020
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bronchiectasis

Intervention

Biological:
• Bronchial basal cells
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.

Locations

Country	Name	City	State
China	First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)	Chongqing	Chongqing

Sponsors (3)

Lead Sponsor	Collaborator
Regend Therapeutics	Southwest Hospital, China, Tongji University

Country where clinical trial is conducted

China, 

References & Publications (1)

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. — View Citation

Outcome

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