Cell Therapy in Advanced Chronic Obstructive Pulmonary Disease Patients

May 21, 2016 updated by: João Tadeu Ribeiro Paes, UPECLIN HC FM Botucatu Unesp
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).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • São Paulo
      • Assis, São Paulo, Brazil, 19.806-900
        • Laboratório de Genética e Terapia Celular - GenTe Cel

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

36 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Pulmonary Capacity
Time Frame: 12 months after procedure
Assessed by whole body plethysmography, measured in liters.
12 months after procedure

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pulmonary morphology
Time Frame: 9 months after procedure
Chest x-ray
9 months after procedure
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).
12 months after procedure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UPECLIN HC FM Botucatu Unesp

Collaborators

Faculdade de Medicina do ABC
IEP São Lucas - Instituto de Ensino e Pesquisa
Hemocentro São Lucas
CordCell

Investigators

  • 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 and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2015

Primary Completion (Anticipated)

October 1, 2016

Study Completion (Anticipated)

April 1, 2017

Study Registration Dates

First Submitted

March 24, 2015

First Submitted That Met QC Criteria

April 8, 2015

First Posted (Estimate)

April 9, 2015

Study Record Updates

Last Update Posted (Estimate)

May 24, 2016

Last Update Submitted That Met QC Criteria

May 21, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • pacientes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Chronic Obstructive Pulmonary Disease (COPD)

Clinical Trials on Bone marrow harvesting

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Georgia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe