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Cell Therapy in Advanced Chronic Obstructive Pulmonary Disease Patients

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ClinicalTrials.gov Identifier: NCT02412332
Recruitment Status : Unknown
Verified May 2016 by João Tadeu Ribeiro Paes, UPECLIN HC FM Botucatu Unesp.
Recruitment status was:  Enrolling by invitation
First Posted : April 9, 2015
Last Update Posted : May 24, 2016
Sponsor:
Collaborators:
Faculdade de Medicina do ABC
IEP São Lucas - Instituto de Ensino e Pesquisa
Hemocentro São Lucas
CordCell
Information provided by (Responsible Party):
João Tadeu Ribeiro Paes, UPECLIN HC FM Botucatu Unesp

Brief Summary:
The purpose of this study is to determine whether cell therapy with autologous adult stem cells (from bone marrow and/or fat) is safe in the treatment of advanced Chronic Obstructive Pulmonary Disease (COPD).

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease (COPD) Procedure: Bone marrow harvesting Procedure: Liposuction Phase 1 Phase 2

Detailed Description:
Pulmonary emphysema, within the spectrum of Chronic Obstructive Pulmonary Disease (COPD), can be described as the destruction of alveolar walls and enlargement of the airspaces distal to the terminal bronchioles, with inflammatory infiltrate and no detectable fibrosis. Despite significant advances resulting from the introduction of new therapeutic approaches, such as pulmonary rehabilitation, an effective and not only palliative clinical treatment is yet to be achieved. Surgical treatment, in turn, involves highly complex procedures and, in the case of lung transplantation, the shortage of donors. In this context, cell therapy with stem cells is presented as a promising therapeutic alternative with great potential for applicability. The main goal of this study is to evaluate the safety of the infusion of bone marrow mononuclear cells (BMMC), adipose-derived stem cells (ASC), separately or conjugated, in COPD patients. The sample will consist of 20 advanced COPD patients (grade 3 by GOLD criteria). Patients will be, by lot, divided into four distinct groups, namely: Group 1: Control; Group 2: Bone marrow mononuclear cells; Group 3 - Stem cells derived from adipose tissue and Group 4: bone marrow mononuclear cells and stem cells derived from adipose tissue. After the selection of patients, clinical and laboratory evaluation will be conducted (cardiology, laboratory examinations and tests to define the score of dyspnea). The cells used for the cell therapy will be obtained from the patient's own bone marrow or adipose tissue (autologous). The separation of the bone marrow mononuclear (BMMC) will be performed by centrifugation in density gradient (Ficoll), while stem cells derived from adipose tissue will be isolated by enzymatic digestion (collagenase) and cultivation. The infusion will be performed by a peripheral vein (brachial) after preparation, separation, expansion and quality control of the cells. The patients will be followed for a period of 12 months. It is expected that this clinical protocol will allow an expansion in knowledge about cell therapy in pulmonary diseases and represents a significant step towards the establishment of new therapeutic approaches in COPD treatment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cell Therapy in Advanced Chronic Obstructive Pulmonary Disease Patients
Study Start Date : April 2015
Estimated Primary Completion Date : October 2016
Estimated Study Completion Date : April 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: COPD Lung Diseases

Arm Intervention/treatment
No Intervention: Group 1 - Control
The patients will be followed during the course of 12 months and evaluated regarding disease progression. No interventions will be performed other than conventional (in-course) treatment.
Experimental: Group 2 - BMMC
Patients will be submitted to bone marrow harvesting. Bone marrow mononuclear cells (BMMC) will be obtained by Ficoll separation and returned to patients by systemic infusion (1x10^8 BMMC in 30 mL saline). Three patients will be submitted to Lung perfusion scintigraphy with technetium for cell engraftment evaluation.
Procedure: Bone marrow harvesting
Approximately 200 mL of bone marrow will be surgically collect from the iliac crest (pelvis) of the patient under spinal anesthesia.

Experimental: Group 3 - ASC
Patients will be submitted to liposuction. The obtained fat tissue will be cultivated by 21 days and adipose-derived stem cell (ASC) will be returned to patients by systemic infusion (1x10^8 ASC in 30 mL saline). Three patients will be submitted to Lung perfusion scintigraphy with technetium for cell engraftment evaluation.
Procedure: Liposuction
Approximately 50 mL of adipose tissue (fat) will be surgically collected from the abdominal region of the patient under spinal anesthesia.

Experimental: Group 4 - BMMC + ASC
Patients will be submitted to liposuction and the obtained fat tissue will be cultivated by 21 days and adipose-derived stem cell (ASC) obtained. Patients will be submitted to bone marrow harvesting and bone marrow mononuclear cells (BMMC) will be obtained by Ficoll separation. BMMC and ASC will be returned to patients by systemic infusion (5x10^7 ASC + 5x10^7 BMMC in 30 mL saline). Three patients will be submitted to Lung perfusion scintigraphy with technetium for cell engraftment evaluation.
Procedure: Bone marrow harvesting
Approximately 200 mL of bone marrow will be surgically collect from the iliac crest (pelvis) of the patient under spinal anesthesia.

Procedure: Liposuction
Approximately 50 mL of adipose tissue (fat) will be surgically collected from the abdominal region of the patient under spinal anesthesia.




Primary Outcome Measures :
  1. Total Pulmonary Capacity [ Time Frame: 12 months after procedure ]
    Assessed by whole body plethysmography, measured in liters.


Secondary Outcome Measures :
  1. Pulmonary morphology [ Time Frame: 9 months after procedure ]
    Chest x-ray

  2. Pulmonary function [ Time Frame: 12 months after procedure ]
    A composite measure of pulmonary capacity (volume), assessed by plethysmography and spirometry and composed of: Total Pulmonary Capacity (TPC), Forced Vital Capacity (FVC), Forced Expiratory Volume (FEV1) , FEV1/FVC, Forced Expiratory Fraction (FEF 25-75), Residual Volume (RV), TPC/RV and airway Resistance (R).



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Ages Eligible for Study:   40 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • COPD patients with persistent dyspnea in stage 2 or 3 of the dyspnea scale score;
  • Eligibility for pulmonary rehabilitation program;
  • No smoking or smoking cessation for at least 6 months.

Exclusion Criteria:

  • Absence of emphysema on chest tomography;
  • Pulmonary or extrapulmonary infection or active infection history in less than 3 months;
  • History of coronary artery disease and/or severe ventricular dysfunction (ejection fraction <55%);
  • Presence of pulmonary hypertension, ie, estimated systolic pulmonary artery pressure above 35 mmHg at transthoracic Doppler echocardiography;
  • Patients in home oxygen therapy;
  • Advanced renal failure (serum creatinine greater than 1.5 mg / dL) and liver failure CHILD B or C;
  • Immunosuppressive or infectious diseases detected;
  • Patients with known malignancies or collagen diseases;
  • Psycho-social problems, drug and/or alcohol abuse and not obedient to the established medical protocol;
  • No family acceptance;
  • Pregnancy or at risk of pregnancy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02412332


Locations
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Brazil
Laboratório de Genética e Terapia Celular - GenTe Cel
Assis, São Paulo, Brazil, 19.806-900
Sponsors and Collaborators
UPECLIN HC FM Botucatu Unesp
Faculdade de Medicina do ABC
IEP São Lucas - Instituto de Ensino e Pesquisa
Hemocentro São Lucas
CordCell
Investigators
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Study Chair: Selma D Squassoni, MD Faculdade de Medicina do ABC
Study Chair: Ellie Fiss, MD Faculdade de Medicina do ABC
Study Chair: Elíseo J Sekya IEP São Lucas - Instituto de Ensino e Pesquisa
Study Chair: Adelson Alves, Dr Hemocentro São Lucas
Study Chair: Andressa Forte TechLife
Study Chair: Larissa C Zanutto IEP São Lucas - Instituto de Ensino e Pesquisa

Publications:
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Responsible Party: João Tadeu Ribeiro Paes, Professor, UPECLIN HC FM Botucatu Unesp
ClinicalTrials.gov Identifier: NCT02412332     History of Changes
Other Study ID Numbers: pacientes
First Posted: April 9, 2015    Key Record Dates
Last Update Posted: May 24, 2016
Last Verified: May 2016

Keywords provided by João Tadeu Ribeiro Paes, UPECLIN HC FM Botucatu Unesp:
advanced COPD (stage III)
Adult stem cells
Cell therapy

Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases