Post-radiotherapy Pulmonary FibrosisPhase 1NCT02277145
A Study on Radiation-induced Pulmonary Fibrosis Treated With Clinical Grade Umbilical Cord Mesenchymal Stem Cells
A Phase 1 study testing clinical grade umbilical cord mesenchymal stem cells in people with Post-radiotherapy Pulmonary Fibrosis, run by Jianwu Dai at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Post-radiotherapy Pulmonary Fibrosis
- What is being tested?
- clinical grade umbilical cord mesenchymal stem cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- Oct 2014to Dec 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, 18-70 years old.
- Subjects with a clear history of malignancy.
- Subjects with a clear history of chest radiation therapy at least 3 months earlier.
- Subjects diagnosed as chronic phase of radiation-induced pneumonitis or radiation-induced pulmonary fibrosis stage (see Annex 3 for diagnosis).
- Subjects signed informed consent.
Who cannot join
- 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 with progression-free survival (PFS) less than 0.5 years or Karnofsky performance scores less than 60 points.
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
Chongqing, Chongqing Municipality, 400038
About this study
Official title: Phase I Study of Radiation-induced Pulmonary Fibrosis Treated With Clinical Grade Umbilical Cord Mesenchymal Stem Cells
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.
- Conditions
- Post-radiotherapy Pulmonary Fibrosis
- Being tested
- clinical grade umbilical cord mesenchymal stem cells
- Keywords
- radiation-induced pulmonary fibrosis, MSCs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
clinical grade umbilical cord mesenchymal stem cellsBiological
10^6 (1 million) /Kg/person cells of clinical grade umbilical cord MSCs will be injected after fully lavage of the localized lesions
| Study group | Role | What they receive |
|---|---|---|
| treatment group | Experimental | 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 Receives: Biological: clinical grade umbilical cord mesenchymal stem cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite indicators, including quantitative analysis of CT density histograms, self-evaluation and changes of TGF-β1 content
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.
Measured: 6 months
Safety Evaluation
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.
Measured: 6 months
Secondary outcomes (24)
Clinical Indicator 1: change in blood gas analysis
Measured: 3-6 months
Clinical Indicator 2: change in pulmonary function analysis
Measured: 3-6 months
Clinical Indicator 3: 6-minute walk test distance
Measured: 3-6 months
Clinical Indicator 4: change in MRC chronic dyspnea scale
Measured: 3-6 months
Clinical Indicator 5: change in St. George's Respiratory Questionnaire (SGRQ) scale
Measured: 3-6 months
Immunological Indicator in serum 1: T lymphocyte counts in peripheral blood
Cellular immunological indicator: T lymphocyte counts in peripheral blood measured in serum
Measured: 3-6 months
Immunological Indicator in serum 2: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2)
Cellular immunological indicator: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2) measured in serum
Measured: 3-6 months
Immunological Indicator in serum 3: concent of immunoglobulin
Humoral immunological indicator: concent of immunoglobulin measured in serum
Measured: 3-6 months
Immunological Indicator in serum 4: expression levels of various cytokines (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc)
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
Measured: 3-6 months
Immunological Indicator in serum 5: subtype analysis and phagocytic activity analysis of macrophage
Macrophage-related polarization indicator: subtype analysis and phagocytic activity of macrophage measured in serum
Measured: 3-6 months
Immunological Indicator in serum 6: expression levels of IL-12, IL-10
Macrophage- related polarization indicators: expression levels of IL-12, IL-10 measured in serum
Measured: 3-6 months
Immunological Indicator in lavage fluid 1: T lymphocyte counts in peripheral blood
Cellular immunological indicator: T lymphocyte counts in peripheral blood measured in lavage fluid
Measured: 6 months
Immunological Indicator in lavage fluid 2: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2)
Cellular immunological indicator: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2) measured in lavage fluid
Measured: 6 months
Immunological Indicator in lavage fluid 3: concent of immunoglobulin
Humoral immunological indicator: concent of immunoglobulin measured in lavage fluid
Measured: 6 months
Immunological Indicator in lavage fluid 4: expression levels of various cytokines (IL-1, IL-3, IL-6, IL-8, TNF-α, GM-CSF, etc)
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
Measured: 6 months
Immunological Indicator in lavage fluid 5: subtype analysis and phagocytic activity analysis of macrophage
Macrophage-related polarization indicator: subtype analysis and phagocytic activity of macrophage measured in lavage fluid
Measured: 6 months
Immunological Indicator in lavage fluid 6: expression levels of IL-12, IL-10
Macrophage-related polarization indicators: expression levels of IL-12, IL-10 measured in lavage fluid
Measured: 6 months
Inflammatory Indicators: measured by routine blood test including C-reactive protein (CRP)
Measured: 3 months
Fibrosis Indicators in serum 1: content of transforming growth factor -α/β (TGF-α/TGF-β)
Content of transforming growth factor α/β (TGF-α/TGF-β) measured in serum
Measured: 3-6 months
Fibrosis Indicators in serum 2: content of hydroxyproline
Content of hydroxyproline measured in serum
Measured: 3-6 months
Fibrosis Indicators in serum 3: content of matrix metalloproteinase 1/7(MMP1/MMP7)
Content of matrix metalloproteinase 1/7(MMP1/MMP7) measured in serum
Measured: 3-6 months
Fibrosis Indicators in lavage fluid 1: content of transforming growth factor -α/β (TGF-α/TGF-β)
Content of transforming growth factor -α/β (TGF-α/TGF-β) measured in lavage fluid
Measured: 6 months
Fibrosis Indicators in lavage fluid 2: content of hydroxyproline
Content of hydroxyproline measured in lavage fluid measured in lavage fluid
Measured: 6 months
Fibrosis Indicators in lavage fluid 3: content of matrix metalloproteinase 1/7(MMP1/MMP7)
Content of matrix metalloproteinase 1/7(MMP1/MMP7) measured in lavage fluid
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2014 (estimated)
- Study startOct 2014
- Primary completionDec 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-radiotherapy Pulmonary FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jianwu Dai
- Sponsor type
- Other government
- Collaborators
- Southwest Hospital, China
- Responsible party
- Sponsor-investigator, Jianwu Dai, Chinese Academy of Sciences
- Investigators
- JianWu Dai, Ph.D, Principal investigator, Chinese Academy of SciencesWei Xiong, M.D, Study chair, First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)Xiaotian Dai, M.M, Study director, First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02277145
- Sponsor's protocol ID
- CAS-XDA001-SH/IGDB
- Status last verified
- Jul 2018
- First submitted
- 20 Oct 2014
- Last updated
- 24 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Radiation-induced Pulmonary Fibrosis Treated With Clinical Grade Umbilical Cord Mesenchymal Stem Cells
- ClinicalTrials.gov ID
- NCT02277145
- Acronym / sponsor ID
- CAS-XDA001-SH/IGDB
- Conditions
- Post-radiotherapy Pulmonary Fibrosis
- Keywords
- radiation-induced pulmonary fibrosis, MSCs
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Jianwu DaiOther government
- Collaborators
- Southwest Hospital, China
- Study start
- Oct 2014
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 28 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| treatment group | Experimental | Biological: clinical grade umbilical cord mesenchymal stem cellsPatients 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female, 18-70 years old.
- Subjects with a clear history of malignancy.
- Subjects with a clear history of chest radiation therapy at least 3 months earlier.
- Subjects diagnosed as chronic phase of radiation-induced pneumonitis or radiation-induced pulmonary fibrosis stage (see Annex 3 for diagnosis).
- Subjects signed informed consent.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| clinical grade umbilical cord mesenchymal stem cells10^6 (1 million) /Kg/person cells of clinical grade umbilical cord MSCs will be injected after fully lavage of the localized lesions | Biological | treatment group |
Primary outcome
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.
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.
24 secondary outcomes
Clinical Indicator 1: change in blood gas analysis
Time frame: 3-6 months
Clinical Indicator 2: change in pulmonary function analysis
Time frame: 3-6 months
Clinical Indicator 3: 6-minute walk test distance
Time frame: 3-6 months
Clinical Indicator 4: change in MRC chronic dyspnea scale
Time frame: 3-6 months
Clinical Indicator 5: change in St. George's Respiratory Questionnaire (SGRQ) scale
Time frame: 3-6 months
Immunological Indicator in serum 1: T lymphocyte counts in peripheral blood
Time frame: 3-6 months
Immunological Indicator in serum 2: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2)
Time frame: 3-6 months
Immunological Indicator in serum 3: concent of immunoglobulin
Time frame: 3-6 months
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
Immunological Indicator in serum 5: subtype analysis and phagocytic activity analysis of macrophage
Time frame: 3-6 months
Immunological Indicator in serum 6: expression levels of IL-12, IL-10
Time frame: 3-6 months
Immunological Indicator in lavage fluid 1: T lymphocyte counts in peripheral blood
Time frame: 6 months
Immunological Indicator in lavage fluid 2: response level of CD4+ T lymphocyte subsets (such as Th1 / Th2)
Time frame: 6 months
Immunological Indicator in lavage fluid 3: concent of immunoglobulin
Time frame: 6 months
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
Immunological Indicator in lavage fluid 5: subtype analysis and phagocytic activity analysis of macrophage
Time frame: 6 months
Immunological Indicator in lavage fluid 6: expression levels of IL-12, IL-10
Time frame: 6 months
Inflammatory Indicators: measured by routine blood test including C-reactive protein (CRP)
Time frame: 3 months
Fibrosis Indicators in serum 1: content of transforming growth factor -α/β (TGF-α/TGF-β)
Time frame: 3-6 months
Fibrosis Indicators in serum 2: content of hydroxyproline
Time frame: 3-6 months
Fibrosis Indicators in serum 3: content of matrix metalloproteinase 1/7(MMP1/MMP7)
Time frame: 3-6 months
Fibrosis Indicators in lavage fluid 1: content of transforming growth factor -α/β (TGF-α/TGF-β)
Time frame: 6 months
Fibrosis Indicators in lavage fluid 2: content of hydroxyproline
Time frame: 6 months
Fibrosis Indicators in lavage fluid 3: content of matrix metalloproteinase 1/7(MMP1/MMP7)
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2019.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
JianWu Dai, Ph.D principal investigator
Chinese Academy of Sciences
Wei Xiong, M.D study chair
First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
Xiaotian Dai, M.M study director
First Affiliated Hospital of the Third Military University, PLA (Southwest Hospital)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing clinical grade umbilical cord mesenchymal stem cells in people with Post-radiotherapy Pulmonary Fibrosis, run by Jianwu Dai at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite indicators, including quantitative analysis of CT density histograms, self-evaluation and changes of TGF-β1 content (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2019.