Safety Study of Bone-marrow Derived Mesenchymal Stromal Cells Associated With Endobronchial Valves in Emphysema

Study Overview
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Brief Summary
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The combined use of one-way endobronchial valves and bone-marrow derived mesenchymal stromal cells in patients with severe pulmonary emphysema is safe and will contribute to increase quality of life.

Detailed Description
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In addition to testing the safety of one-way endobronchial valves combined with bone-marrow derived mesenchymal stromal cells, the study will determine the systemic inflammatory potential of cell therapy measured by C-reactive protein levels (CRP), erythrocyte sedimentation rate (ESR) and complete blood count in peripheral blood. Finally, the study will aim at determining if other markers of inflammatory response and remodeling are modulated by this therapy.

Official Title
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Bone-marrow Derived Mesenchymal Stromal Cells Associated With One-way Endobronchial Valves in Patients With Pulmonary Emphysema: Safety Study

Conditions
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Pulmonary Emphysema

Intervention / Treatment
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* Procedure: Bronchoscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of severe heterogeneous emphysema (heterogeneity > 15%), with heterogeneity defined as the difference between lobes in the percent area covered by parenchymal density greater than -950 Hounsfield Units. Estimation of collateral ventilation based on fissure with integrity ≥ 75%. Total lung capacity> 100% predicted. Residual volume> 150% predicted. Forced expiratory volume at the first minute <45% predicted. Diffusing capacity of the lungs for carbon monoxide <45% predicted. Optimal medical treatment. Limitations in daily physical activities. Minimum of 4 months without smoking Having family support. Stage ≥ 2 in modified Medical Research Council Dyspnea Scale (MMRC). Exclusion Criteria: Homogenous emphysema. Presence of collateral ventilation. Use of systemic corticosteroids (prednisone> 20mg/day or equivalent). Pulmonary or extrapulmonary infection. Coronary heart disease and/or severe ventricular dysfunction. Significant renal or liver disease. Immunosuppressive disease. Active smoking. Cancer prognosis with survival <2 years. Psychosocial problems. Pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Valves plus cells<br>Bronchoscopy Five patients will be selected to receive bone-marrow derived mesenchymal stromal cells delivered bronchoscopically right before insertion of one-way endobronchial valves. | Procedure: Bronchoscopy<br>* Bronchoscopic delivery of one-way valves and bone-marrow derived mesenchymal stromal cells.<br>|
| Placebo Comparator: Valves plus saline<br>Bronchoscopy Five patients will be selected for treatment with one-way endobronchial valves only, with saline injected prior to valve insertion. | Procedure: Bronchoscopy<br>* Bronchoscopic delivery of one-way valves and bone-marrow derived mesenchymal stromal cells.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absence of lung deficits during the procedure and/or in the 4 months follow-up |  | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life | St. George Respiratory Questionnaire | 120 days | 
| Pulmonary function | Spirometry, flow-volume curve, post-bronchodilator test, determination of residual volume, airway resistance by plethysmography, diffusing capacity of the lung for carbon monoxide, and six-minute walk test | 120 days | 
| Inflammation | Collection of blood samples for determination of C-reactive protein (CRP), erythrocyte | 120 days |