Clinical trial NCT02277145: A Study on Radiation-induced Pulmonary Fibrosis Treated With Clinical Grade Umbilical Cord Mesenchymal Stem Cells
Official title: Phase I Study of Radiation-induced Pulmonary Fibrosis Treated With Clinical Grade Umbilical Cord Mesenchymal Stem Cells
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Post-radiotherapy Pulmonary Fibrosis
Keywords: radiation-induced pulmonary fibrosis
MSCs
Lead sponsor: Chinese Academy of Sciences
Sponsor class: OTHER_GOV
Collaborators: name: Southwest Hospital, China
First posted: 2014-10-28
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Composite indicators, including quantitative analysis of CT density histograms, self-evaluation and changes of TGF-β1 content
timeFrame: 6 months
measure: Safety Evaluation
timeFrame: 6 months
Secondary outcomes:
measure: Clinical Indicator 1: change in blood gas analysis
timeFrame: 3-6 months
measure: Clinical Indicator 2: change in pulmonary function analysis
timeFrame: 3-6 months
measure: Clinical Indicator 3: 6-minute walk test distance
timeFrame: 3-6 months
measure: Clinical Indicator 4: change in MRC chronic dyspnea scale
timeFrame: 3-6 months
measure: Clinical Indicator 5: change in St. George's Respiratory Questionnaire (SGRQ) scale
timeFrame: 3-6 months
measure: Immunological Indicator in serum 1: T lymphocyte counts in peripheral blood
timeFrame: 3-6 months
measure: Immunological Indicator in serum 2: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2)
timeFrame: 3-6 months
measure: Immunological Indicator in serum 3: concent of immunoglobulin
timeFrame: 3-6 months
measure: Immunological Indicator in serum 4: expression levels of various cytokines (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc)
timeFrame: 3-6 months
measure: Immunological Indicator in serum 5: subtype analysis and phagocytic activity analysis of macrophage
timeFrame: 3-6 months
measure: Immunological Indicator in serum 6: expression levels of IL-12, IL-10
timeFrame: 3-6 months
measure: Immunological Indicator in lavage fluid 1: T lymphocyte counts in peripheral blood
timeFrame: 6 months
measure: Immunological Indicator in lavage fluid 2: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2)
timeFrame: 6 months
measure: Immunological Indicator in lavage fluid 3: concent of immunoglobulin
timeFrame: 6 months
measure: Immunological Indicator in lavage fluid 4: expression levels of various cytokines (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc)
timeFrame: 6 months
measure: Immunological Indicator in lavage fluid 5: subtype analysis and phagocytic activity analysis of macrophage
timeFrame: 6 months
measure: Immunological Indicator in lavage fluid 6: expression levels of IL-12, IL-10
timeFrame: 6 months
measure: Inflammatory Indicators: measured by routine blood test including C-reactive protein (CRP)
timeFrame: 3 months
measure: Fibrosis Indicators in serum 1: content of transforming growth factor -α/β (TGF-α/TGF-β)
timeFrame: 3-6 months
measure: Fibrosis Indicators in serum 2: content of hydroxyproline
timeFrame: 3-6 months
measure: Fibrosis Indicators in serum 3: content of matrix metalloproteinase 1/7(MMP1/MMP7)
timeFrame: 3-6 months
measure: Fibrosis Indicators in lavage fluid 1: content of transforming growth factor -α/β (TGF-α/TGF-β)
timeFrame: 6 months
measure: Fibrosis Indicators in lavage fluid 2: content of hydroxyproline
timeFrame: 6 months
measure: Fibrosis Indicators in lavage fluid 3: content of matrix metalloproteinase 1/7(MMP1/MMP7)
timeFrame: 6 months
Other outcomes:
Locations:
city: Chongqing
country: China
facility: First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
state: Chongqing
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
References: