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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Incidence of Treatment-Emergent Adverse Events (Safety Evaluation)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, 18-70 years old.
- •Subjects had exposed to dusts with a long history.
- •Subjects with a clear clinical diagnosis to be silicotics or coal miners' pneumoconiosis patients.
- •Subjects with each detected index of pulmonary function test including FVC, FEV1 or MVV had exceeded 70% of the predicated value.
- •Subjects signed informed consent.
排除标准
- •Women of childbearing age at the stage of pregnancy or lactation, or those without taking effective contraceptive measures.
- •Subjects with syphilis or HIV positive antibody.
- •Subjects with infection aggravated within the past month.
- •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..
- •Subjects suffering from other serious diseases, such as myocardial infarction, unstable angina, cirrhosis, and acute glomerulonephritis.
- •Subjects suffering from other life-threatening diseases with an estimated life-span less than 2 years.
- •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.
- •Subjects with severe renal impairment, serum creatinine> 1.5 times the upper limit of normal.
- •Subjects with liver disease or liver damage: ALT, AST, total bilirubin> 2 times 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.
- •Subjects accepted large volume whole-lung lavage treatment previously.
研究组 & 干预措施
Control Group
Large volume whole-lung lavage (WLL) only
干预措施: large volume whole-lung lavage (WLL) (Procedure)
Experimental Group
Combined large volume WLL with clinical grade umbilical cord mesenchymal stem cells transplantation
干预措施: large volume whole-lung lavage (WLL) (Procedure)
Experimental Group
Combined large volume WLL with clinical grade umbilical cord mesenchymal stem cells transplantation
干预措施: clinical grade umbilical cord mesenchymal stem cells (Biological)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events (Safety Evaluation)
时间窗: 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 histograms
时间窗: 6 months after surgery
次要结局
- Immunological Indicator in lavage fluid: expression levels of various cytokines including TNF-α, IL1-β, MIP-1α, TIMP1, PDGF(6 months)
- self-evaluation(6 months)
- Clinical Indicator 2: change in MRC chronic dyspnea scale(6 months)
- Fibrosis Indicators in lavage fluid: expression levels of TGF-β1, hydroxyproline, MMP2, MMP9(6 months)
- Immunological Indicator in lavage fluid : response level of CD4+ T lymphocyte subsets (Th1/Th2/Th17)(6 months)
- Clinical Indicator 1: change in blood gas analysis(6 months)
- Clinical Indicator 3: change in St. George's Respiratory Questionnaire (SGRQ) scale(6 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, PDGF(6 months)
- Fibrosis Indicators in serum: expression levels of TGF-β1, hydroxyproline, MMP2, MMP9(6 months)
研究者
Jianwu Dai
Principal Investigator of Regenerative Medicine Laboratory, Institute of Genetics and Developmental Biology, CAS
Chinese Academy of Sciences