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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

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ClinicalTrials.gov Identifier: NCT01849159
Recruitment Status : Withdrawn
First Posted : May 8, 2013
Last Update Posted : January 9, 2018
Sponsor:
Information provided by (Responsible Party):
Alexander Averyanov, Federal Research Clinical Center of Federal Medical & Biological Agency, Russia

Tracking Information
First Submitted Date  ICMJE April 24, 2013
First Posted Date  ICMJE May 8, 2013
Last Update Posted Date January 9, 2018
Study Start Date  ICMJE March 2014
Estimated Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 5, 2013)
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01849159 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 5, 2013)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Emphysema
Intervention  ICMJE
  • 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
  • Other: Reference therapy: 400 mL of 0.9% NaCl solution
Study Arms  ICMJE
  • 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
    Intervention: Biological: Mesenchymal stem cells
  • Placebo Comparator: Control Group
    400 mL of 0.9% NaCl solution. Infusions will be performed every 2 months for 1 year
    Intervention: Other: Reference therapy: 400 mL of 0.9% NaCl solution
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: January 8, 2018)
0
Original Estimated Enrollment  ICMJE
 (submitted: May 5, 2013)
30
Estimated Study Completion Date  ICMJE June 2017
Estimated Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Russian Federation
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01849159
Other Study ID Numbers  ICMJE MSC-HYP-01
FMBA-FRCC-MSC-01 ( Other Identifier: Federal Medical&Biological Agency )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alexander Averyanov, Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
Study Sponsor  ICMJE Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alexander V Averyanov, MD, PhD Federal Research Clinical Center of Federal Medical and Biological Agency
PRS Account Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP