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

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

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.

Study Overview

• Status: Completed
• Conditions: Pneumoconiosis
• Intervention / Treatment: Procedure: large volume whole-lung lavage (WLL); Biological: clinical grade umbilical cord mesenchymal stem cells

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400038
      • First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Nanjing Chest Hosptial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Group; Large volume whole-lung lavage (WLL) only	Procedure: large volume whole-lung lavage (WLL); Generally 1000 ~ 2000ml each time, 14 ~ 10 times totally, each side of the lung to 20 ~ 15 liters, until the lavage fluid from the black into a colorless clear clarification
Experimental: Experimental Group; Combined large volume WLL with clinical grade umbilical cord mesenchymal stem cells transplantation	Procedure: large volume whole-lung lavage (WLL); Generally 1000 ~ 2000ml each time, 14 ~ 10 times totally, each side of the lung to 20 ~ 15 liters, until the lavage fluid from the black into a colorless clear clarification; Biological: clinical grade umbilical cord mesenchymal stem cells; 10^6 (1 million) /Kg/person cells of clinical grade umbilical cord MSCs will be injected after whole-lung lavage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events (Safety Evaluation)	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.	6 months
Imaging indicator: Quantitative analysis of CT density histograms		6 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Indicator 1: change in blood gas analysis	Including PH, PaCO2,PaO2, HCO3	6 months
Clinical Indicator 2: change in MRC chronic dyspnea scale		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 lavage fluid : 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
Immunological Indicator in lavage fluid: 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
Fibrosis Indicators in lavage fluid: expression levels of TGF-β1, hydroxyproline, MMP2, MMP9		6 months
self-evaluation	Self-evaluation will be also classified into four levels: effective, improved, stable and invalid	6 months

Collaborators and Investigators

• Sponsor: Jianwu Dai
• Collaborators: Southwest Hospital, China; Nanjing Chest Hospital
• Investigators: Study Chair: Wei Xiong, M.D, First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital); Study Director: Xiaotian Dai,, M.M, First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital); Study Director: Yingming Zhang, M.M, Nanjing Chest Hospital; Study Director: Shencun Fang, M.M, Nanjing Chest Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: January 20, 2016
• First Submitted That Met QC Criteria: January 26, 2016
• First Posted (Estimate): January 29, 2016

Study Record Updates

• Last Update Posted (Actual): July 24, 2019
• Last Update Submitted That Met QC Criteria: July 23, 2019
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Mesenchymal Stem Cells; Pneumoconiosis; whole-lung lavage (WLL)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Occupational Diseases; Lung Diseases, Interstitial; Lung Injury; Pneumoconiosis
• Other Study ID Numbers: CAS-XDA-SH/NCH/IGDB