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A Study on Pneumoconiosis Treated With Whole-lung Lavage Combined With Mesenchymal Stem Cells

Phase 1
Completed
Conditions
Pneumoconiosis
Interventions
Procedure: large volume whole-lung lavage (WLL)
Biological: clinical grade umbilical cord mesenchymal stem cells
Registration Number
NCT02668068
Lead Sponsor
Jianwu Dai
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
80
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Control Grouplarge volume whole-lung lavage (WLL)Large volume whole-lung lavage (WLL) only
Experimental Grouplarge volume whole-lung lavage (WLL)Combined large volume WLL with clinical grade umbilical cord mesenchymal stem cells transplantation
Experimental Groupclinical grade umbilical cord mesenchymal stem cellsCombined large volume WLL with clinical grade umbilical cord mesenchymal stem cells transplantation
Primary Outcome Measures
NameTimeMethod
Incidence of Treatment-Emergent Adverse Events (Safety Evaluation)6 months

Clinical adverse events evaluated as definitely/ probably/possibly concerned with large volume lung lavage and / or mesenchymal stem cell therapy in this trial, and abnormal results of laboratory tests or other special examinations will be observed and recorded in detail.

Imaging indicator: Quantitative analysis of CT density histograms6 months after surgery
Secondary Outcome Measures
NameTimeMethod
Immunological Indicator in lavage fluid : response level of CD4+ T lymphocyte subsets (Th1/Th2/Th17)6 months
Immunological Indicator in lavage fluid: expression levels of various cytokines including TNF-α, IL1-β, MIP-1α, TIMP1, PDGF6 months
self-evaluation6 months

Self-evaluation will be also classified into four levels: effective, improved, stable and invalid

Clinical Indicator 2: change in MRC chronic dyspnea scale6 months
Fibrosis Indicators in lavage fluid: expression levels of TGF-β1, hydroxyproline, MMP2, MMP96 months
Clinical Indicator 1: change in blood gas analysis6 months

Including PH, PaCO2,PaO2, HCO3

Clinical Indicator 3: change in St. George's Respiratory Questionnaire (SGRQ) scale6 months
Immunological Indicator in serum : response level of CD4+ T lymphocyte subsets (Th1/Th2/Th17)6 months
Immunological Indicator in serum : expression levels of various cytokines including TNF-α, IL1-β, MIP-1α, TIMP1, PDGF6 months
Fibrosis Indicators in serum: expression levels of TGF-β1, hydroxyproline, MMP2, MMP96 months

Trial Locations

Locations (2)

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

🇨🇳

Chongqing, Chongqing, China

Nanjing Chest Hosptial

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Nanjing, Jiangsu, China

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