Clinical Study of the Efficacy and Safety of the Application of Allogeneic Mesenchymal (Stromal) Cells of Bone Marrow, Cultured Under the Hypoxia in the Treatment of Patients With Severe Pulmonary Emphysema
Actively developing stem cells (SCs) transplantation techniques cause natural interest to the problem of regeneration in the lungs. Numerous experimental studies proved the benefits of different types of SCs in experimental models of pulmonary emphysema (PE).
G. Zhen et al. have shown that the transplantation of mesenchymal stem cells (MSCs) to rats with papain-induced emphysema leads to their migration into the lungs, differentiation into type 2 alveolocytes, and inhibition of apoptosis and prevention PE.
K. Schweitzer et al. have proved the activity of inflammation in the airways, alveolocytes and endothelial cells apoptosis decreased after adipose SCs intravenous administration to mice with emphysema caused by chronic exposure to tobacco smoke or VEGF receptors blockade. The study of E.P. Ingenito et al. found that endobronchial installed MSCs engraft into the alveolar wall and peribronchial interstitium and release integrins, extracellular matrix components (collagen IV, laminin and fibrillin), platelet-derived growth factor receptor and transforming growth factor β2.
Our study also found reliable deterrent effect of allogeneic bone marrow MSCs on the development of elastase-induced emphysema in rats at different terms of transplantation.
After the success of pilot studies have started clinical trials. Currently, the website http://www. ClinicalTrials.gov reported three studies evaluating the efficacy and safety of MSC transplantation in patients with COPD and emphysema. Two of them have already been completed and the results of the first pilot project published.
Authors on the example of 4 patients showed a complete absence of adverse effects, improved quality of life and stability of functional parameters at 12 months after starting treatment One of the problems of MSC transplantation in patients with respiratory failure is an accelerated apoptosis of transplanted cells under the influence of proinflammatory cytokines and oxidative stress. Since it is proved that preconditioning MSCs under hypoxia increases their survival in hypoxic conditions, increases the expression of growth factors and antiinflammatory cytokines, we suppose that MSCs grown in hypoxic medium may have a significant positive effect on the disease.
|Pulmonary Emphysema||Biological: Mesenchymal stem cells Other: Reference therapy: 400 mL of 0.9% NaCl solution||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Clinical Study of the Efficacy and Safety of the Application of Allogeneic Mesenchymal (Stromal) Cells of Bone Marrow, Cultured Under the Hypoxia in the Treatment of Patients With Severe Pulmonary Emphysema|
- Safety compared with placebo [ Time Frame: 1 year ]
Mortality (Baseline and 2 years after procedure) Adverse effects and reactions to the treatment(Baseline and 2 years after procedure).
Vital signs (pulse rate, systolic and diastolic arterial blood pressure) (Baseline and 2 years after procedure)
- Change from baseline in the lung tissue density measured by CT-densitometry at6, 12, 24 months [ Time Frame: 2 years ]
- DLCO change from baseline at 6, 12, 24 months [ Time Frame: 2 years ]
- Change from baseline in the functional parameters (FEV1, TLC, RV, FEV1/FVC) at 6,12,18,24 months [ Time Frame: 2 years ]
- Dynamics of the physical capacity (by the 6-min test results) [ Time Frame: 2 years ]
- Dynamics of the blood gas composition (PaO2, PaCO2) [ Time Frame: 2 years ]
- Dynamics of serum level IL-6, TNF-α, Leptin [ Time Frame: 2 years ]
- Quality of life indices by the questionnaire (SF-36) [ Time Frame: 2 years ]
- Number and frequency of exacerbations [ Time Frame: 2 years ]
- Body mass index [ Time Frame: 2 years ]
|Study Start Date:||March 2014|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Active Comparator: MSC group
Intravenous infusion of MSC suspension, pre-conditioned under 1% oxygen, in the amount of 200 mln. cells per 400 mL of sodium chloride physiological solution. Infusions will be performed every 2 months for 1 year
Biological: Mesenchymal stem cells
Intravenous infusion of MSC suspension, pre-conditioned under 1% oxygen, in the amount of 200 mln. cells per 400 mL of sodium chloride physiological solution
Placebo Comparator: Control Group
400 mL of 0.9% NaCl solution. Infusions will be performed every 2 months for 1 year
|Other: Reference therapy: 400 mL of 0.9% NaCl solution|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01849159
|Federal Research Clinical Center of Federal Medical and Biological Agency of Russia||Recruiting|
|Moscow, Moscow region, Russian Federation, 115682|
|Contact: Alexander V Averyanov, MD, PhD +7(495) 395-0511 firstname.lastname@example.org|
|Principal Investigator: Alexander V Averyanov, MD, PhD|
|Principal Investigator:||Alexander V Averyanov, MD, PhD||Federal Research Clinical Center of Federal Medical and Biological Agency|