Safety and Feasibility Study of Administration of Mesenchymal Stemcells for Treatment of Emphysema
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01306513|
Recruitment Status : Completed
First Posted : March 2, 2011
Last Update Posted : November 19, 2012
|Condition or disease||Intervention/treatment||Phase|
|Emphysema||Biological: autologous bone marrow derived mesenchymal stromal cells||Phase 1|
Hide Detailed Description
Study Rationale Emphysema is one of the two main components of chronic obstructive pulmonary disease (COPD) and contributes over many years to airway obstruction by the loss of elastic recoil around the smallest airways. Emphysema is induced by cigarette smoking and it is widely accepted that the disease is caused by excessive proteolytic activity by proteases and a chronic inflammatory process, characterized by a cellular influx consisting of macrophages, neutrophils and T cells. This inflammatory response is steroid resistant and leads to slow but persistent alveolar destruction, resulting in enlarged lungs with bullous parts in both lungs. In addition to a central role of innate immunity, recent studies suggest that also (auto)antigen specific immunity may play a role in the pathogenesis of COPD.
Currently, the only treatment available for severe emphysema is lung volume reduction surgery (LVRS) to remove the most destroyed parts of the lungs. The surgery is generally performed in two separate sessions with a 10-12 weeks interval, with each lung as a separate surgical target. This surgical treatment allows improved ventilation in the remaining less affected areas of the lungs as demonstrated by post-surgical clinical improvement of lung function and increased survival in a subgroup of patients. Delayed wound healing after LVRS is an important clinical problem. It may lead to prolonged hospital stay due to air leakage from the lungs into the thoracic cavity. Lung emphysema patients are at high risk for prolonged air leakage after this surgery, which is most likely explained by the inflammatory process related to the disease.
Mesenchymal stromal cells (MSC) are multipotent cells that can differentiate into several cell types, including fibroblasts, osteoblasts, adipocytes and chondrocyte progenitors. In recent years it has become evident that bone-marrow derived MSC (BM-MSC) have potent immunomodulatory effects on T and B cells and in animal models of chronic inflammation in vivo. In addition, it has been shown that MSC express or release a variety of soluble factors implicated in anti-apoptotic signaling and cell growth. Importantly, encouraging results have recently been obtained with the treatment of severe steroid resistant Graft versus Host Disease (GvHD) with donor (allogeneic) BM-MSC. Furthermore, in our institute autologous BM-MSC are currently under investigation for treatment of tissue injury due to autoimmune disease (Crohn's Disease) and allogeneic immune responses (renal transplant recipients with biopsy proven subclinical rejection). The combination of the immunosuppressive, growth-potentiating and anti-apoptotic properties of BM-MSC may lead to accelerated wound healing after LVRS and might induce lung repair. In the present phase I study the investigators will assess the safety and feasibility of intravenous (i.v.) administration of BM-MSC prior to LVRS in a small group of severe pulmonary emphysema patients. Results of this safety and feasibility study may lead to future studies on the use of BM-MSC for immunomodulation and induction of repair in patients with pulmonary emphysema and milder stages of COPD.
Objective To test the safety and feasibility of intravenous administration of autologous BM-MSC after one-sided LVRS and prior to a second LVRS procedure for patients with severe pulmonary emphysema.
Study design Open label, non-randomized, non-blinded, prospective clinical trial. Patients are operated in two sessions; initially on one lung without pre-surgical infusion of BM-MSC, followed by a second surgical procedure on the contralateral lung which is preceded by two i.v. infusions of BM-MSC one week apart, 4 and 3 weeks prior to the lung surgery.
Study population Patients of at least 40 years of age with end-stage emphysema who are eligible for lung volume reduction surgery.
Intervention The intervention consists of two doses of BM-MSC infusions in 10 patients with a one week interval, 4 and 3 weeks prior to the second LVRS respectively.
1. 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. Toxicity criteria will be evaluated by grade according to WHO.
- Difference in days between post-surgical transpleural air leak of the lung in each patient after the first (no infusion of BM-MSC) and second surgical (3 weeks after the last i.v. infusion of BM-MSC) intervention.
- Histological responses in resected lung tissue (measured by immunohistochemistry of markers of inflammation, fibrosis and repair).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Effect of Autologous Bone Marrow Derived Mesenchymal Stromal Cells Prior to Lung Volume Reduction Surgery for Severe Pulmonary Emphysema- a Phase I Safety and Feasibility Study|
|Study Start Date :||October 2010|
|Actual Primary Completion Date :||June 2012|
|Actual Study Completion Date :||November 2012|
Biological: autologous bone marrow derived mesenchymal stromal cells
Intravenous administration of autologous bone marrow-derived mesenchymal stromal cells.
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 8 weeks ]
Safety: rate and grade of (serious) adverse events in the study population using the WHO toxicity criteria. After infusion of MSC's investigators will score change in renal function, breathing rate, temperature, heart rate, and blood pressure.
Feasibility: determination of the number of expanded MSCs in relation to the amount of autologous bone marrow collected, number of passages required and time to reach to study target dose
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): NCT01306513
|Department of Pulmonology, Leiden University Medical Center|
|Leiden, Netherlands, 2333 ZA|
|Study Chair:||Jan Stolk, MD, PhD||Leiden University Medical Center|