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

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Emphysema
• Intervention / Treatment: Procedure: Bronchoscopy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • PR
    • Curitiba, PR, Brazil, 80215-901
      • Pontifícia Universidade Católica do Paraná
  • RJ
    • Rio de Janeiro, RJ, Brazil, 21941-902
      • Universidade Federal do Rio de Janeiro
  • RS
    • Porto Alegre, RS, Brazil, 90035-003
      • Hospital de Clinicas de Porto Alegre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Collaborators: Ministry of Health, Brazil; Conselho Nacional de Desenvolvimento Científico e Tecnológico; Rio de Janeiro State Research Supporting Foundation (FAPERJ); Universidade Federal do Rio de Janeiro; Pontifícia Universidade Católica do Paraná; National Research Council, Brazil
• Investigators: Principal Investigator: Patricia RM Rocco, MD, PhD, Universidade Federal do Rio de Janeiro; Principal Investigator: Hugo G Oliveira, MD, PhD, Hospital de Clinicas de Porto Alegre

Publications and helpful links

General Publications

• de Oliveira HG, Macedo-Neto AV, John AB, Jungblut S, Prolla JC, Menna-Barreto SS, Fortis EA. Transbronchoscopic pulmonary emphysema treatment: 1-month to 24-month endoscopic follow-up. Chest. 2006 Jul;130(1):190-9. doi: 10.1378/chest.130.1.190.
• Abreu SC, Antunes MA, Pelosi P, Morales MM, Rocco PR. Mechanisms of cellular therapy in respiratory diseases. Intensive Care Med. 2011 Sep;37(9):1421-31. doi: 10.1007/s00134-011-2268-3. Epub 2011 Jun 9.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: June 5, 2013
• First Submitted That Met QC Criteria: June 5, 2013
• First Posted (Estimate): June 7, 2013

Study Record Updates

• Last Update Posted (Estimate): March 25, 2015
• Last Update Submitted That Met QC Criteria: March 24, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Emphysema
• Other Study ID Numbers: 13-0150