Cell Therapy in Advanced Chronic Obstructive Pulmonary Disease Patients

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

Official title:

Cell Therapy in Advanced Chronic Obstructive Pulmonary Disease Patients

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02412332
• Other study ID #: pacientes
• Status: Enrolling by invitation
• Phase: Phase 1/Phase 2
• First received: March 24, 2015
• Last updated: May 21, 2016
• Start date: April 2015
• Est. completion date: April 2017

Study information

• Verified date: May 2016
• Source: UPECLIN HC FM Botucatu Unesp
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 20
• Est. completion date: April 2017
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

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

Locations

Country	Name	City	State
Brazil	Laboratório de Genética e Terapia Celular - GenTe Cel	Assis	São Paulo

Sponsors (5)

Lead Sponsor	Collaborator
UPECLIN HC FM Botucatu Unesp	CordCell, Faculdade de Medicina do ABC, Hemocentro São Lucas, Instituto de Ensino e Pesquisa São Lucas

Country where clinical trial is conducted

Brazil, 

References & Publications (3)

Ribeiro-Paes JT, Bilaqui A, Greco OT, Ruiz MA, Marcelino MY, Stessuk T, de Faria CA, Lago MR. Unicentric study of cell therapy in chronic obstructive pulmonary disease/pulmonary emphysema. Int J Chron Obstruct Pulmon Dis. 2011 Jan 1;6:63-71. doi: 10.2147/COPD.S15292. — View Citation

Ribeiro-Paes JT, Stessuk T, Marcelino M, Faria C, Marinelli T, Ribeiro-Paes MJ. A protocol proposition of cell therapy for the treatment of chronic obstructive pulmonary disease. Rev Port Pneumol. 2014 Mar-Apr;20(2):84-91. doi: 10.1016/j.rppneu.2013.06.008. Epub 2013 Nov 26. English, Portuguese. — View Citation

Stessuk T, Ruiz MA, Greco OT, Bilaqui A, Ribeiro-Paes MJ, Ribeiro-Paes JT. Phase I clinical trial of cell therapy in patients with advanced chronic obstructive pulmonary disease: follow-up of up to 3 years. Rev Bras Hematol Hemoter. 2013;35(5):352-7. doi: 10.5581/1516-8484.20130113. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Pulmonary Capacity	Assessed by whole body plethysmography, measured in liters.	12 months after procedure	No
Secondary	Pulmonary morphology	Chest x-ray	9 months after procedure	No
Secondary	Pulmonary function	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	No