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Autologous Bronchial Basal Cells Transplantation for Treatment of Bronchiectasis

Primary Purpose

Bronchiectasis

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Bronchial basal cells

About this trial

This is an interventional treatment trial for Bronchiectasis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bronchial basal cells

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

6-minute walk distance test

MRC chronic dyspnea scale

St. George's Respiratory Questionnaire (SGRQ) scale

inflammation indicators

TNF-α,IL1-β,PDGF,MMP9,TIMP1,CRP, PCT

fibrotic factor level

TGF-β, Hydroxyproline

incidence of acute exacerbation

patients' self-evaluation

The self-efficacy evaluation can also be classified into four levels: effective, improved, stable and invalid.

blood gas level（PH）

blood gas level（HCO3）

blood gas level（PaCO2）

blood gas level（PaO2）

pulmonary function test (DLco)

Diffusing capacity of CO

pulmonary function test (FEV1)

Forced expiratory volume in one second, FEV1

pulmonary function test (FVC)

forced vital capacity

pulmonary function test (MVV)

maximal voluntary ventilation

pulmonary function test (MMEF)

maximal midexpiratory flow curve

Full Information

NCT ID

NCT02722642

First Posted

March 9, 2016

Last Updated

March 17, 2020

Sponsor

Regend Therapeutics

Collaborators

Southwest Hospital, China, Tongji University

1. Study Identification

Unique Protocol Identification Number

NCT02722642

Brief Title

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

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Unknown status

Study Start Date

March 2016 (undefined)

Primary Completion Date

June 2020 (Anticipated)

Study Completion Date

June 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Regend Therapeutics

Collaborators

Southwest Hospital, China, Tongji University

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Bronchiectasis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Bronchial basal cells

Arm Type

Experimental

Arm Description

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.

Intervention Type

Biological

Intervention Name(s)

Bronchial basal cells

Intervention Description

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.

Primary Outcome Measure Information:

Title

CT imaging of dilated bronchi

Description

CT image of dilated bronchi will be analyzed.Clinical indicators include the spread of dilation, extent of dilation and the thickness of bronchi wall.

Time Frame

3 day - 6 months

Secondary Outcome Measure Information:

Title

6-minute walk distance test

Time Frame

3 day - 6 months

Title

MRC chronic dyspnea scale

Time Frame

3 day - 6 months

Title

St. George's Respiratory Questionnaire (SGRQ) scale

Time Frame

3 day - 6 months

Title

inflammation indicators

Description

TNF-α,IL1-β,PDGF,MMP9,TIMP1,CRP, PCT

Time Frame

3 day - 6 months

Title

fibrotic factor level

Description

TGF-β, Hydroxyproline

Time Frame

3 day - 6 months

Title

incidence of acute exacerbation

Time Frame

3 day-6 months

Title

patients' self-evaluation

Description

The self-efficacy evaluation can also be classified into four levels: effective, improved, stable and invalid.

Time Frame

3 day - 6 months

Title

blood gas level（PH）

Time Frame

3 day - 6 months

Title

blood gas level（HCO3）

Time Frame

3 day - 6 months

Title

blood gas level（PaCO2）

Time Frame

3 day - 6 months

Title

blood gas level（PaO2）

Time Frame

3 day - 6 months

Title

pulmonary function test (DLco)

Description

Diffusing capacity of CO

Time Frame

3 day - 6 months

Title

pulmonary function test (FEV1)

Description

Forced expiratory volume in one second, FEV1

Time Frame

3 day - 6 months

Title

pulmonary function test (FVC)

Description

forced vital capacity

Time Frame

3 day - 6 months

Title

pulmonary function test (MVV)

Description

maximal voluntary ventilation

Time Frame

3 day - 6 months

Title

pulmonary function test (MMEF)

Description

maximal midexpiratory flow curve

Time Frame

3 day - 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Wei Zuo, Ph.D.

Phone

+86-21-65985082

zuow@regend.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Xiaotian Dai, M.D.

Phone

+86-23-68765681

daixt1973@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Wei Zuo, Ph.D.

Organizational Affiliation

Regend Therapeutics Co.Ltd

Official's Role

Study Chair

Facility Information:

Facility Name

First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)

City

Chongqing

State/Province

Chongqing

ZIP/Postal Code

400038

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xiaotian Dai, M.D.

Phone

86-23-68765681

daixt1973@163.com

First Name & Middle Initial & Last Name & Degree

Wei Zuo, Ph.D.

Phone

86-10-65985082

zuow@regend.cn

First Name & Middle Initial & Last Name & Degree

Ting Zhang, Ph.D.

First Name & Middle Initial & Last Name & Degree

Yu Ma, Ph.D.

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

25383540

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.

Results Reference

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Autologous Bronchial Basal Cells Transplantation for Treatment of Bronchiectasis

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