Autologous Transplantation of Bronchial Basal Cells for Treatment of COPD

NCT03655795 | Unknown Phase 1

• 1 other identifier: 201809
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

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).

Conditions

COPD

Outcome Measures

Primary Outcomes (1)

• Diffusing capacity of the lung for carbon monoxide (DLCO)

  An indicator for pulmonary function

  6 months -1 year

Secondary Outcomes (10)

• Forced expiratory volume measured at the first second (FEV1)

  6 months -1 year

• Forced vital capacity (FVC)

  6 months -1 year

• The ratio of forced expiratory volume in the first one second to the forced vital capacity (FEV1/FVC)

  6 months -1 year

• Maximum Mid Expiratory Flow (MMF)

  6 months -1 year

• Maximum Voluntary Ventilation (MVV)

  6 months -1 year

Study Arms (1)

Bronchial basal cells

EXPERIMENTAL

Autologous transplantation of bronchial basal cells

Biological: Bronchial basal cells

Interventions

Bronchial basal cells BIOLOGICAL

Autologous transplantation of bronchial basal cells

Bronchial basal cells

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ruijin Hospital: lead
• Regend Therapeutics: collaborator

Related Publications (2)

• 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.

  PMID: 25383540 BACKGROUND

• 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.

  PMID: 29344809 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yun Feng, M.D., Ph.D

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jieming Qu, M.D., Ph.D

CONTACT

+86-21-64370045; jmqu0906@163.com

Wei Zuo, Ph. D

CONTACT

+86-21-65985082; zuow@regend.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 22, 2018
• First Posted: August 31, 2018
• Study Start: November 1, 2018
• Primary Completion: September 1, 2020
• Study Completion: March 1, 2021
• Last Updated: November 6, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share