Clinical trial NCT02668068: A Study on Pneumoconiosis Treated With Whole-lung Lavage Combined With Mesenchymal Stem Cells
Official title: A Multicenter, Randomized, Single-blind, Parallel-group Study of Combined Large Volume WLL With Clinical Grade Umbilical Cord Mesenchymal Stem Cells(MSC) Transplantation for Treatment of Pneumoconiosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pneumoconiosis
Keywords: Pneumoconiosis
Mesenchymal Stem Cells
whole-lung lavage (WLL)
Lead sponsor: Chinese Academy of Sciences
Sponsor class: OTHER_GOV
Collaborators: name: Southwest Hospital, China
name: Nanjing Chest Hospital
First posted: 2016-01-29
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Pneumoconiosis is a kind of lung disease due to inhalation of dust such as silica(common named Silicosis), coal and rock dust, characterized by inflammation, coughing, and fibrosis. Currently there is no effective drug treatment. The whole-lung lavage(WLL) can effectively clear the protein-like substances and inhaled dust deposited in the alveoli and bronchioles, as well as the pulmonary alveolar macrophage(PAM) and the resulting induced inflammation, fibrosis induced factor, serve to improve respiratory function, relieve symptoms of efficacy, but can't slow down or reverse the progression of pulmonary fibrosis.

By taking large volume whole-lung lavage (WLL) as a conventional therapy, this study intends to observe and evaluate the safety and efficiency of combined large volume WLL with mesenchymal stem cell (MSC) transplantation for treatment of Pneumoconiosis. Moreover, the immune regulation effect between large volume WLL and combined large volume WLL with MSC transplantation will also be preliminarily investigated and discussed.


Eligibility criteria: Inclusion Criteria:

1. Male or female, 18-70 years old.
2. Subjects had exposed to dusts with a long history.
3. Subjects with a clear clinical diagnosis to be silicotics or coal miners' pneumoconiosis patients.
4. Subjects with each detected index of pulmonary function test including FVC, FEV1 or MVV had exceeded 70% of the predicated value.
5. Subjects signed informed consent.

Exclusion Criteria:

1. Women of childbearing age at the stage of pregnancy or lactation, or those without taking effective contraceptive measures.
2. Subjects with syphilis or HIV positive antibody.
3. Subjects with infection aggravated within the past month.
4. Subjects suffering from any of the following pulmonary diseases: active tuberculosis, pulmonary embolism, pneumothorax, multiple huge bullae, uncontrolled asthma, severe pneumonia, acute exacerbation of chronic bronchitis, AECOPD, severe and / or extremely severe COPD, etc..
5. Subjects suffering from other serious diseases, such as myocardial infarction, unstable angina, cirrhosis, and acute glomerulonephritis.
6. Subjects suffering from other life-threatening diseases with an estimated life-span less than 2 years.
7. Subjects with leukopenia (WBC less than 4x109 / L) or agranulocytosis (WBC less than 1.5x109 / L or neutrophils less than 0.5x109 / L) caused by any reason.
8. Subjects with severe renal impairment, serum creatinine\> 1.5 times the upper limit of normal.
9. Subjects with liver disease or liver damage: ALT, AST, total bilirubin\> 2 times the upper limit of normal
10. Subjects with a history of mental illness or suicide risk, with a history of epilepsy or other central nervous system disorders.
11. 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.
12. Subjects with a history of alcohol or illicit drug abuse.
13. Subjects accepted by any other clinical trials within 3 months before the enrollment.
14. Subjects with poor compliance, difficult to complete the study.
15. Any other conditions that might increase the risk of subjects or interfere with the clinical trial.
16. Subjects accepted large volume whole-lung lavage treatment previously.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events (Safety Evaluation)
timeFrame: 6 months
measure: Imaging indicator: Quantitative analysis of CT density histograms
timeFrame: 6 months after surgery
Secondary outcomes:
measure: Clinical Indicator 1: change in blood gas analysis
timeFrame: 6 months
measure: Clinical Indicator 2: change in MRC chronic dyspnea scale
timeFrame: 6 months
measure: Clinical Indicator 3: change in St. George's Respiratory Questionnaire (SGRQ) scale
timeFrame: 6 months
measure: Immunological Indicator in serum : response level of CD4+ T lymphocyte subsets (Th1/Th2/Th17)
timeFrame: 6 months
measure: Immunological Indicator in lavage fluid : response level of CD4+ T lymphocyte subsets (Th1/Th2/Th17)
timeFrame: 6 months
measure: Immunological Indicator in serum : expression levels of various cytokines including TNF-α, IL1-β, MIP-1α, TIMP1, PDGF
timeFrame: 6 months
measure: Immunological Indicator in lavage fluid: expression levels of various cytokines including TNF-α, IL1-β, MIP-1α, TIMP1, PDGF
timeFrame: 6 months
measure: Fibrosis Indicators in serum: expression levels of TGF-β1, hydroxyproline, MMP2, MMP9
timeFrame: 6 months
measure: Fibrosis Indicators in lavage fluid: expression levels of TGF-β1, hydroxyproline, MMP2, MMP9
timeFrame: 6 months
measure: self-evaluation
timeFrame: 6 months
Other outcomes:
Locations:
city: Chongqing
country: China
facility: First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
state: Chongqing
city: Nanjing
country: China
facility: Nanjing Chest Hosptial
state: Jiangsu
Study officials:
affiliation: Chinese Academy of Sciences
name: JianWu Dai, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
name: Wei Xiong, M.D
role: STUDY_CHAIR
affiliation: First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
name: Xiaotian Dai,, M.M
role: STUDY_DIRECTOR
affiliation: Nanjing Chest Hospital
name: Yingming Zhang, M.M
role: STUDY_DIRECTOR
affiliation: Nanjing Chest Hospital
name: Shencun Fang, M.M
role: STUDY_DIRECTOR
References: