Clinical trial NCT01849159: 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
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Pulmonary Emphysema
Keywords: Mesenchymal stem cells
Hypoxia
Emphysema
Lead sponsor: Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
Sponsor class: OTHER_GOV
First posted: 2013-05-08
Enrollment: 0
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* HRCT-confirmed diagnosis of lung emphysema by two independent radiologists
* post-bronchodilator FEV1/FVC ratio \< 0.7
* post-bronchodilator FEV1 % predicted value ≥ 20% and \< 50%
* age 35 and 75 years of, of either sex, and of any race
* current or ex-smoker, with a cigarette smoking history ≥ 10 pack-years

Exclusion Criteria:

* • asthma or other clinically relevant lung disease other than COPD (e.g. restrictive lung diseases, sarcoidosis, tuberculosis, idiopathic pulmonary fibrosis, or lung cancer)

  * α1-Antitrypsin deficiency
  * Presence of bullae (more than 10 cm in the diameter)
  * active infection within 4 weeks of screening
  * significant exacerbation of COPD or has required mechanical ventilation within 4 weeks of screening
  * clinically relevant uncontrolled medical condition not associated with COPD
  * documented history of uncontrolled heart failure
  * pulmonary hypertension due to left heart condition
  * Subject has evidence of active malignancy, or prior history of active malignancy
  * Subject has a life expectancy of \< 6 months

Primary outcomes:
measure: Safety compared with placebo
timeFrame: 1 year
Secondary outcomes:
measure: Change from baseline in the lung tissue density measured by CT-densitometry at6, 12, 24 months
timeFrame: 2 years
measure: DLCO change from baseline at 6, 12, 24 months
timeFrame: 2 years
measure: Change from baseline in the functional parameters (FEV1, TLC, RV, FEV1/FVC) at 6,12,18,24 months
timeFrame: 2 years
measure: Dynamics of the physical capacity (by the 6-min test results)
timeFrame: 2 years
measure: Dynamics of the blood gas composition (PaO2, PaCO2)
timeFrame: 2 years
measure: Dynamics of serum level IL-6, TNF-α, Leptin
timeFrame: 2 years
measure: Quality of life indices by the questionnaire (SF-36)
timeFrame: 2 years
measure: Number and frequency of exacerbations
timeFrame: 2 years
measure: Body mass index
timeFrame: 2 years
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Federal Research Clinical Center of Federal Medical and Biological Agency of Russia
state: Moscow Region
Study officials:
affiliation: Federal Research Clinical Center of Federal Medical and Biological Agency
name: Alexander V Averyanov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: