Clinical trial NCT03021681: An Exploratory Study on the Treatment of Chronic Obstructive Pulmonary Disease With Autologous Bronchial Basal Cell Transplantation
Official title: Huai'an First People 's Hospital,Nanjing Medical University
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cell Transplantation
Lead sponsor: Huai'an No.1 People's Hospital
Sponsor class: OTHER
Collaborators: name: Regend Therapeutics
First posted: 2017-01-16
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Between November 2016 and November 2019, the investigators initially recruited 20 with stable COPD patients. Primary evaluations including medical history, physical examination, anthropometric data, blood routine, blood biochemistry, blood coagulation, electrocardiogram,high resolution chest CT, arterial blood gas, pulmonary function test,6-min walking test(6MWT),modified medical research council(MMRC),St George's respiratory questionnaire(SGRQ). After initial evaluation, the investigators obtained extraction bronchial basal cells micro tissue from 3\~4 grade bronchus to by mean of fiberbronchoscopy, then purified and selectively amplified bronchial basal cells to reserve .The basal layer cell culture system for our partners (Regend Therapeutics) patented technology using culture medium containing special combination of growth factors and composite materials to simulated composite basal layer environment and can selectively amplified bronchial basal cells, while other types of mature epithelial cells and fibroblasts could not grow naturally. 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 . Estimate the change of respiratory function(symptoms, signs, chest CT, pulmonary function, the 6 minute walk test, MMRC, SGRQ etc) and serum index in third days , first months, third months, sixth months and first years of the follow-up after treatment respectively, to evaluate the safety and efficiency of autologous bronchial basal cells for treatment of COPD .

Eligibility criteria: Inclusion Criteria:

1. aged between 18 to 70 years
2. 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)
3. CT imaging and hematological examination excluded other lung diseases.
4. stable disease for more than 2 weeks
5. patients who were able to tolerate fiberoptic bronchoscopy
6. to sign the informed consent form

Exclusion Criteria:

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

Primary outcomes:
measure: forced expiratory volume in one second(FEV1)
timeFrame: 24 months
measure: chest high-resolution computed tomography
timeFrame: 24 months
measure: arterial blood gas
timeFrame: 24 months
measure: 6MWT
timeFrame: 24 months
Secondary outcomes:
measure: forced vital capacity(FVC)
timeFrame: 24 months
measure: MMRC
timeFrame: 24 months
measure: SGRQ
timeFrame: 24 months
Other outcomes:
Locations:
city: Huai'an
country: China
facility: Huai'an First People's Hospital
state: Jiangsu
Study officials:
affiliation: Regend Therapeutics,Suzhou Industry Park,Suzhou,CHINA
name: Wei Zuo, PhD
role: STUDY_CHAIR
References:
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.
citation: 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.
citation: 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.