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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
Sponsor:
Information provided by (Responsible Party):
Alexander Averyanov, Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
ClinicalTrials.gov Identifier:
NCT01849159
First received: April 24, 2013
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Pulmonary Emphysema
Biological: Mesenchymal stem cells
Other: Reference therapy: 400 mL of 0.9% NaCl solution
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by Federal Research Clinical Center of Federal Medical & Biological Agency, Russia:

Primary Outcome Measures:
  • Safety compared with placebo [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

    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)



Secondary Outcome Measures:
  • Change from baseline in the lung tissue density measured by CT-densitometry at6, 12, 24 months [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • DLCO change from baseline at 6, 12, 24 months [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Change from baseline in the functional parameters (FEV1, TLC, RV, FEV1/FVC) at 6,12,18,24 months [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Dynamics of the physical capacity (by the 6-min test results) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Dynamics of the blood gas composition (PaO2, PaCO2) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Dynamics of serum level IL-6, TNF-α, Leptin [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Quality of life indices by the questionnaire (SF-36) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Number and frequency of exacerbations [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Body mass index [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: March 2014
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   35 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01849159

Locations
Russian Federation
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    averyanovav@mail.ru   
Principal Investigator: Alexander V Averyanov, MD, PhD         
Sponsors and Collaborators
Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
Investigators
Principal Investigator: Alexander V Averyanov, MD, PhD Federal Research Clinical Center of Federal Medical and Biological Agency
  More Information

No publications provided

Responsible Party: Alexander Averyanov, Deputy of Director General of FRCC, Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
ClinicalTrials.gov Identifier: NCT01849159     History of Changes
Other Study ID Numbers: MSC-HYP-01, FMBA-FRCC-MSC-01
Study First Received: April 24, 2013
Last Updated: August 4, 2014
Health Authority: Russia: Federal Medical and Biological Agency
Russia: Ethics Committee

Keywords provided by Federal Research Clinical Center of Federal Medical & Biological Agency, Russia:
Mesenchymal stem cells
Hypoxia
Emphysema

Additional relevant MeSH terms:
Emphysema
Pulmonary Emphysema
Pathologic Processes
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Diseases
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014