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A Study on Radiation-induced Pulmonary Fibrosis Treated With Clinical Grade Umbilical Cord Mesenchymal Stem Cells

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ClinicalTrials.gov Identifier: NCT02277145
Recruitment Status : Active, not recruiting
First Posted : October 28, 2014
Last Update Posted : July 18, 2018
Sponsor:
Collaborator:
Southwest Hospital, China
Information provided by (Responsible Party):
Jianwu Dai, Chinese Academy of Sciences

Brief Summary:
Radiation therapy is one of the main means for treating malignant tumor, during which radioactive lung injury is inevitable. Currently there is nearly no effective clinical treatment for late post-radiotherapy pulmonary fibrosis. This study intends to carry out an open, single-center, non-randomized phase I clinical trial. During the treatment, the local lesions will be fully lavaged, and then clinical grade umbilical cord mesenchymal stem cells (MSCs) will be injected directly into the lesion by fiberoptic bronchoscopy. After six-month observation, the investigators will initially evaluate the safety and effectiveness of the treatment by measuring two key indicators-the CT density histogram and the patients' self-evaluation, and one secondary indicator—the changes of TGF-β1 contents, both before and after the treatment. Meanwhile, the investigators will make a preliminary discuss about the possible immunomodulatory effects of the umbilical cord MSCs.

Condition or disease Intervention/treatment Phase
Post-radiotherapy Pulmonary Fibrosis Biological: clinical grade umbilical cord mesenchymal stem cells Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Radiation-induced Pulmonary Fibrosis Treated With Clinical Grade Umbilical Cord Mesenchymal Stem Cells
Study Start Date : October 2014
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : December 31, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: treatment group
Patients will receive 10^6 (1 million) /Kg/person cells of clinical grade umbilical cord mesenchymal stem cells (MSCs) injected via fiberoptic bronchoscopy after fully lavage of the localized lesions
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 fully lavage of the localized lesions




Primary Outcome Measures :
  1. Composite indicators, including quantitative analysis of CT density histograms, self-evaluation and changes of TGF-β1 content [ Time Frame: 6 months ]
    Different proportions will be assigned to the three indicators. The overall curative effect can be judged with scores ranging from 0 to100. Specific proportions are as follows: full scores of 50 points for image changes, 25 for self-efficacy evaluation and 25 for TGF-β1 content changes. The image changes can be classified into four levels: significant control, improved, stable, and progressive; the self-efficacy evaluation can also be classified into four levels: effective, improved, stable and invalid; the changes of TGF-β1 content will be classified into three levels: improved, stable, and progressive. The four levels will be scored on the ratio of 5:4:3:1, the three levels will be scored on the ratio of 5:3:1.

  2. Safety Evaluation [ Time Frame: 6 months ]
    Clinical adverse events evaluated as definitely/ probably/possibly concerned with stem cell therapy in this trial and abnormal results of laboratory tests or other special examinations will be observed and recorded in detail.


Secondary Outcome Measures :
  1. Clinical Indicator 1: change in blood gas analysis [ Time Frame: 3-6 months ]
  2. Clinical Indicator 2: change in pulmonary function analysis [ Time Frame: 3-6 months ]
  3. Clinical Indicator 3: 6-minute walk test distance [ Time Frame: 3-6 months ]
  4. Clinical Indicator 4: change in MRC chronic dyspnea scale [ Time Frame: 3-6 months ]
  5. Clinical Indicator 5: change in St. George's Respiratory Questionnaire (SGRQ) scale [ Time Frame: 3-6 months ]
  6. Immunological Indicator in serum 1: T lymphocyte counts in peripheral blood [ Time Frame: 3-6 months ]
    Cellular immunological indicator: T lymphocyte counts in peripheral blood measured in serum

  7. Immunological Indicator in serum 2: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2) [ Time Frame: 3-6 months ]
    Cellular immunological indicator: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2) measured in serum

  8. Immunological Indicator in serum 3: concent of immunoglobulin [ Time Frame: 3-6 months ]
    Humoral immunological indicator: concent of immunoglobulin measured in serum

  9. Immunological Indicator in serum 4: expression levels of various cytokines (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc) [ Time Frame: 3-6 months ]
    Humoral immunological indicator: expression levels of various cytokines in serum (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc) measured in serum

  10. Immunological Indicator in serum 5: subtype analysis and phagocytic activity analysis of macrophage [ Time Frame: 3-6 months ]
    Macrophage-related polarization indicator: subtype analysis and phagocytic activity of macrophage measured in serum

  11. Immunological Indicator in serum 6: expression levels of IL-12, IL-10 [ Time Frame: 3-6 months ]
    Macrophage- related polarization indicators: expression levels of IL-12, IL-10 measured in serum

  12. Immunological Indicator in lavage fluid 1: T lymphocyte counts in peripheral blood [ Time Frame: 6 months ]
    Cellular immunological indicator: T lymphocyte counts in peripheral blood measured in lavage fluid

  13. Immunological Indicator in lavage fluid 2: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2) [ Time Frame: 6 months ]
    Cellular immunological indicator: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2) measured in lavage fluid

  14. Immunological Indicator in lavage fluid 3: concent of immunoglobulin [ Time Frame: 6 months ]
    Humoral immunological indicator: concent of immunoglobulin measured in lavage fluid

  15. Immunological Indicator in lavage fluid 4: expression levels of various cytokines (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc) [ Time Frame: 6 months ]
    Humoral immunological indicator: expression levels of various cytokines (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc) measured in lavage fluid

  16. Immunological Indicator in lavage fluid 5: subtype analysis and phagocytic activity analysis of macrophage [ Time Frame: 6 months ]
    Macrophage-related polarization indicator: subtype analysis and phagocytic activity of macrophage measured in lavage fluid

  17. Immunological Indicator in lavage fluid 6: expression levels of IL-12, IL-10 [ Time Frame: 6 months ]
    Macrophage-related polarization indicators: expression levels of IL-12, IL-10 measured in lavage fluid

  18. Inflammatory Indicators: measured by routine blood test including C-reactive protein (CRP) [ Time Frame: 3 months ]
  19. Fibrosis Indicators in serum 1: content of transforming growth factor -α/β (TGF-α/TGF-β) [ Time Frame: 3-6 months ]
    Content of transforming growth factor α/β (TGF-α/TGF-β) measured in serum

  20. Fibrosis Indicators in serum 2: content of hydroxyproline [ Time Frame: 3-6 months ]
    Content of hydroxyproline measured in serum

  21. Fibrosis Indicators in serum 3: content of matrix metalloproteinase 1/7(MMP1/MMP7) [ Time Frame: 3-6 months ]
    Content of matrix metalloproteinase 1/7(MMP1/MMP7) measured in serum

  22. Fibrosis Indicators in lavage fluid 1: content of transforming growth factor -α/β (TGF-α/TGF-β) [ Time Frame: 6 months ]
    Content of transforming growth factor -α/β (TGF-α/TGF-β) measured in lavage fluid

  23. Fibrosis Indicators in lavage fluid 2: content of hydroxyproline [ Time Frame: 6 months ]
    Content of hydroxyproline measured in lavage fluid measured in lavage fluid

  24. Fibrosis Indicators in lavage fluid 3: content of matrix metalloproteinase 1/7(MMP1/MMP7) [ Time Frame: 6 months ]
    Content of matrix metalloproteinase 1/7(MMP1/MMP7) measured in lavage fluid



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, 18-70 years old.
  2. Subjects with a clear history of malignancy.
  3. Subjects with a clear history of chest radiation therapy at least 3 months earlier.
  4. Subjects diagnosed as chronic phase of radiation-induced pneumonitis or radiation-induced pulmonary fibrosis stage (see Annex 3 for diagnosis).
  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 with progression-free survival (PFS) less than 0.5 years or Karnofsky performance scores less than 60 points.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02277145


Locations
China, Chongqing
First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
Chongqing, Chongqing, China, 400038
Sponsors and Collaborators
Jianwu Dai
Southwest Hospital, China
Investigators
Principal Investigator: JianWu Dai, Ph.D Chinese Academy of Sciences
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)

Responsible Party: Jianwu Dai, Principal Investigator of Regenerative Medicine Laboratory, Institute of Genetics and Developmental Biology, CAS, Chinese Academy of Sciences
ClinicalTrials.gov Identifier: NCT02277145     History of Changes
Other Study ID Numbers: CAS-XDA001-SH/IGDB
First Posted: October 28, 2014    Key Record Dates
Last Update Posted: July 18, 2018
Last Verified: July 2018

Keywords provided by Jianwu Dai, Chinese Academy of Sciences:
radiation-induced pulmonary fibrosis
MSCs

Additional relevant MeSH terms:
Fibrosis
Pulmonary Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases