Autologous Bronchial Basal Cells Transplantation for Treatment of Bronchiectasis

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

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.

Study Overview

• Status: Unknown
• Conditions: Bronchiectasis
• Intervention / Treatment: Biological: Bronchial basal cells

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400038
      • Recruiting
      • First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
      • Sub-Investigator: Ting Zhang, Ph.D.
      • Sub-Investigator: Yu Ma, Ph.D.
      • Contact: Xiaotian Dai, M.D.; Phone Number: 86-23-68765681; Email: daixt1973@163.com
      • Contact: Wei Zuo, Ph.D.; Phone Number: 86-10-65985082; Email: zuow@regend.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Regend Therapeutics
• Collaborators: Southwest Hospital, China; Tongji University
• Investigators: Study Chair: Wei Zuo, Ph.D., Regend Therapeutics Co.Ltd

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): June 1, 2020

Study Registration Dates

• First Submitted: March 9, 2016
• First Submitted That Met QC Criteria: March 29, 2016
• First Posted (Estimate): March 30, 2016

Study Record Updates

• Last Update Posted (Actual): March 18, 2020
• Last Update Submitted That Met QC Criteria: March 17, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis
• Other Study ID Numbers: 201602301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No