An Exploratory Study on the Treatment of Chronic Obstructive Pulmonary Disease With Autologous Bronchial Basal Cell Transplantation

NCT03021681 | Completed

• 1 other identifier: Huaian1PH2
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic obstructive pulmonary disease(COPD)is characterized by recurrent cough, expectoration and asthma, and eventually develop chronic pulmonary heart disease ,chronic respiratory failure and even death. The current clinical treatments for these patients are symptomatic treatment cannot solve the problem of the damaged lung structure fundamentally. Recent studies show that bronchial basement the layer of cells is a kind of cells in the bronchial epithelial basal layer position, the specific expression of Krt5 antigen with the regeneration and repair of lung function , these cells have the activity similar to adult tissue stem cells. Its division and migration are more active and can continue to produce new cells to complement the death of other types of epithelial cells with functional plasticity which can be used to direct repair the bronchial and alveolar structures. It has been proved that bronchial basal cell transplantation can repair the damaged lungs of experimental animals . The bronchial basal cells from autologous tissue, so there is no immune rejection problem. Also because the bronchial basal cells derived from adult tissues which is a part of the body, so there is no risk of a tumor (in animal experiments, In animal experiments, bronchial basal cells transtracheal input 100 times in human dose still no tumor formation). In the early stage, patients with COPD (2 cases), bronchiectasis (2 cases) and interstitial lung disease (1 case) received the treatment, and the overall effect was good. Diseases were alleviated and recovered to some different extend.The study was to brush bronchial basal cells through fiberbronchoscopy in COPD patients and cultured in vitro, and then through the bronchoscope transfusion to the lesion site. To preliminary evaluate the efficacy and safety of autologous bronchial basal cells in the treatment of chronic obstructive pulmonary disease.

Conditions

Cell Transplantation

Outcome Measures

Primary Outcomes (4)

• forced expiratory volume in one second(FEV1)

  as the severity of chronic obstructive pulmonary disease(COPD)estimated by pulmonary function

  24 months

• chest high-resolution computed tomography

  as the severity of lung hyperinflation estimated by radiological

  24 months

• arterial blood gas

  to assess the level of hypoxemia and hypercapnia in chronic obstructive pulmonary disease(COPD) patients

  24 months

• 6MWT

  6 min walking test, to evaluate the exercise function in patients with moderate and severe pulmonary heart diseases

  24 months

Secondary Outcomes (3)

• forced vital capacity(FVC)

  24 months

• MMRC

  24 months

• SGRQ

  24 months

Study Arms (1)

COPD group(self control)

OTHER

Prior treatment:20 stable COPD patients were enrolled,estimated the respiratory function and serum index Intervention:autologous bronchial basal cell transplantation After treatment:Estimate the change of respiratory function and serum index in third days , first months, third months, sixth months and first years of the follow-up after treatment respectively

Other: autologous bronchial basal cell transplantation

Interventions

autologous bronchial basal cell transplantation OTHER

the investigators obtained extraction bronchial basal cells micro tissue from 3\~4 grade bronchus, then purified and selectively amplified bronchial basal cells to reserve . After a period of time, the basal lamina of the bronchial epithelial cells can be stored in the liquid nitrogen cell bank for a long time. Before applied to the patient, bronchial basal cells need to go through a series of strict examination. Then, bronchoscopy was performed again and the bronchial basal lamina suspension was injected directly into the lesion site .

COPD group(self control)

Eligibility Criteria

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

You may qualify if:

• aged between 18 to 70 years
• according to the guideline criteria, the diagnosis of COPD:
• ①There is a chronic cough, sputum or gas breathing symptoms such as promoting
• ②Pulmonary function tests showed airflow limitation(FEV1\<80% predicted value，FEV1/FVC\<0.7)
• CT imaging and hematological examination excluded other lung diseases.
• stable disease for more than 2 weeks
• patients who were able to tolerate fiberoptic bronchoscopy
• to sign the informed consent form

You may not qualify if:

• women who are pregnant, nursing or not taking effective contraception
• syphilis, HIV antibody positive person
• there is a history of alcohol or illicit drug abuse
• patients who had received any other clinical trial within the first 3 months
• poor compliance, it is difficult to complete the study
• researchers believe there may be any increase in the risk of the subject or any interference with the clinical trial

Sponsors & Collaborators

• Huai'an No.1 People's Hospital: lead
• Regend Therapeutics: collaborator

Study Sites (1)

Huai'an First People's Hospital

Huai'an, Jiangsu, 223300, China

Location

Related Publications (3)

• 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

• Kumar PA, Hu Y, Yamamoto Y, Hoe NB, Wei TS, Mu D, Sun Y, Joo LS, Dagher R, Zielonka EM, Wang de Y, Lim B, Chow VT, Crum CP, Xian W, McKeon F. Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection. Cell. 2011 Oct 28;147(3):525-38. doi: 10.1016/j.cell.2011.10.001.

  PMID: 22036562 BACKGROUND

• Rock JR, Randell SH, Hogan BL. Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling. Dis Model Mech. 2010 Sep-Oct;3(9-10):545-56. doi: 10.1242/dmm.006031. Epub 2010 Aug 10.

  PMID: 20699479 BACKGROUND

Study Officials

• Wei Zuo, PhD

  Regend Therapeutics,Suzhou Industry Park,Suzhou,CHINA

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of respiratory Medicine in Huai'an No.1 People's Hospital

Study Record Dates

• First Submitted: January 12, 2017
• First Posted: January 16, 2017
• Study Start: November 1, 2016
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2021
• Last Updated: March 29, 2022

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)