smokers lungs soft lungs
Conditions
Interventions
Two intravenous infusions of autologous bone marrow derived mesenchymal
stemcells
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: For entry in the study, the following criteria must be met: a) Men and women over 50 years of age and must have stopped smoking for more than 6 months. b) Subject is willing to participate in the study and has signed the informed consent. c) Subject must have emphysema in both lungs demonstrated on a chest CT scan. d) Subjects must have less than 15% difference in lung density between left and right lung as assessed by PulmCMS software in chest CT scan DICOM files. e) Subject must have FEV1 below 40% pred (post-bronchodilator). f) Subject must have a Kco gastransfer factor
Exclusion criteria
Exclusion criteria: a) Patients with clinical and radiological evidence of bronchiectasis. b) Patients suffering from renal- or hepatic failure. c) A psychiatric, addictive, or any disorder that compromises ability to give truly informed consent for participation in this study. d) Use of any investigational drug within 1 month prior to screening e) Patients with pulmonary hypertension, with mean PAP above 30 mmHg assessed by ultrasound of the chest or by transoesophageal ultrasound. f) Documented HIV infection. g) Active hepatitis B, hepatitis C or TB. h) Subjects who currently have or who have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening. i) Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, cardiac, neurologic, or cerebral disease (including demyelinating diseases such as multiple sclerosis). j) Malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence). k) History of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly. l) Known recent substance abuse (drug or alcohol). m) Poor tolerability of venapuncture or lack of adequate venous access for required blood sampling during the study period.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and feasibility of intravenous infusion of two doses of BM-MSC with 1 wk interval after the first LVRS and prior to a second LVRS. Safety will be evaluated according to WHO criteria and in addition change in outcome of lung function by the surgery and MSC treatment will be compared with a cohort of LUMC patients treated by lungvolumereduction surgery in LUMC and of whom similar lung function data were obtained. | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease specific transpleural air leakage measured in days after the day of surgery. The surgeon will insert a chest tube after removal of emphysematous tissue. Transpleural air leakage can be measured with a flow meter connected to drainage reservoir. The number of days with air leakage through the tube will be counted after each LVRS. The difference in days between the first and second LVRS session is the primary outcome parameter Ex-vivo analysis of MSC-induced effects: Immunohistochemical examination of resected tissue of both left (not MSC-treated) and right (MSC-treated) lung from each patient will be analysed for inflammatory cell markers and markers of tissue repair and fibrosis. Inflammatory cell infiltrates will be analyzed using markers for T cells (CD3, CD4 and CD8), B cells (CD20), macrophages (CD68), neutrophils (elastase), eosinophils (EG2), and mast cells (AA1; mast cell tryptase). To assess early fibrotic events, we will determine total collagen deposition and expression of mooth muscle actin, a smooth muscle cell marker that is also expressed in myofibroblasts. Ki67 staining will be used as a marker for proliferating cells, together with VEGF and other markers for tissue repair that will be further defined based on the findings. Finally, we will assess the local expression of hCAP18/LL-37, an antimicrobial peptide that has recently been identified as a chemoattractant for MSC. In this way we will compare MSC-induced effects within patients and between patients. inn-vivo analysis of MSC on lung tissue: Before LVRS and one year after the second LVRS, patients will be assessed for lung density by chest CT scan according to a published acquisition protocol. Both chest CT scans are part of the standard chain of procedures associated with 2-sided LVRS. The difference in 15th percentile point of the histogram of lung densities between left and right lung measured before and after surgery is a secondary end point. Comparison of | — |
Countries
Netherlands
Outcome results
None listed