Study Protocol of Intramyocardial Injection of Autologous Bone Marrow Stem Cells for Refractory Angina

NCT01966042 | Completed Phase 2 Results DMC

• 2 other identifiers: Cell 0314/050314/05
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Therapeutic neovascularization is an innovative strategy for cardiac tissue recovery due to chronic, intense ischemia. Thus stem cell therapy has become a promising procedure for the large number of patients with refractory angina due to coronary disease, despite of the use of multiple anti-angina medications, remain severely symptomatic with disabling angina. Stem cell therapy using autologous cells from the patient's bone marrow, has been shown to be safe and associated with improved myocardial perfusion, reducing the symptoms of advanced coronary artery disease and increasing the functional capacity of patients whose therapeutic armamentarium available today has been exhausted. The study hypothesis was that the infusion of autologous mononuclear cells derived from the patient's bone marrow and delivered via intramyocardial injection in patients with refractory angina and normal or slightly depressed ventricular function, promote improvement in the anginal symptoms and myocardial perfusion by the inducing neoangiogenesis.

Conditions

Refractory Angina

Keywords

Refractory angina; Cell Therapy; Bone Marrow; Mononuclear Cells

Outcome Measures

Primary Outcomes (1)

• Angina Class Variation

  It was evaluated in accordance with the percentage of participants that change the functional class of angina according to CCSAC (Canadian Cardiovascular Society Angina Classification - description below), after treatment. The functional class of angina was also analyzed as an ordinal variable and the median of the functional class was calculated before and after the procedure, at the time of interest (3, 6 and 12 months post treatment), in comparison to baseline, ie. value at 3 months minus value at baseline. Screening of Functional Graduation of Stable Angina: I - Angina only occurs after a fast or prolonged and strenuous effort during work or recreation. II - Slight limitation to everyday activities. III - Considerable limitation of common physical activity. IV - Inability to perform any physical activity without discomfort, the symptoms can be present at rest.

  3, 6 and 12 months

Secondary Outcomes (2)

• Functional Change Evaluation

  Baseline and 12 months

• Functional Change Evaluation

  Baseline, 6 and 12 months

Other Outcomes (1)

• Life Quality

  Baseline and 12 months

Study Arms (1)

Stem Cell Therapy

EXPERIMENTAL

All subjects enrolled in the study underwent: Local Sedation; Bone Marrow Aspiration; Minithoracotomy; Autologous bone marrow mononuclear cells infusion.

Procedure: Local sedation; Procedure: Bone Marrow Aspiration; Procedure: Minithoracotomy; Biological: Autologous bone marrow mononuclear cells infusion

Interventions

Local sedation PROCEDURE

All subjects enrolled in the study underwent local sedation for bone marrow aspiration.

Stem Cell Therapy

Bone Marrow Aspiration PROCEDURE

All subjects enrolled in the study underwent bone marrow aspiration after they had been anesthetized from the posterior iliac crest. The sample was aspirated into a series of sterile syringes and brought to the cell processing room/laboratory. The processing was in accordance to the Standard Operating Procedure developed observing Good Practice Guidelines.

Stem Cell Therapy

Minithoracotomy PROCEDURE

The surgical procedure used as cardiac access route was the left anterolateral thoracotomy or left anterior minithoracotomy, depending on the segment of the left ventricle to be treated, allowing the good access to the viable myocardial areas.

Stem Cell Therapy

Autologous bone marrow mononuclear cells infusion BIOLOGICAL

Once the subject had his or her chest opened and the coronary anatomy reviewed by examination of the pre-operatory nuclear scan to define the area of ischemia, the surgeon drew up the cells into a series of syringes and injected the entire contents of the cell preparation in a series of injections directly into the myocardium.

Stem Cell Therapy

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged above 21 years old;
• Documented coronary artery disease by angiography and confirmed ischemia by myocardial perfusion scintigraphy with physical or pharmacological stress;
• Class IV angina pectoris (CCSAC) that is unresponsive to optimized dose of at least two anti-anginal medications including nitrates, beta blocker, calcium channel blocker or Ranolazine) as well as aspirin or other anti-platelet agent plus statin therapy;
• Considered to not be a candidate for either percutaneous catheter or surgical myocardial revascularization due to either anatomical type, extent of coronary disease in the target vessel, or caliber of the distal vessels;
• Ejection fraction of \> 45% by Transthoracic echocardiogram with Doppler by the Simpson method;
• Myocardial perfusion scintigraphy showing that the areas of myocardial ischemia supply viable tissue.

You may not qualify if:

• Significant Valvular Heart Disease;
• Chronic kidney disease requiring renal replacement therapy;
• Severe comorbidities associated with the reduction of life expectancy in less than 5 years;
• Ongoing abusive use of alcohol or illegal drugs (Based on the Diagnostic and Statistical Manual (DSM) IV - CAGE questionnaire);
• Positive Serologic test for HIV, Human T-cell lymphotrophic virus (HTLV), Hepatitis A, B and C;
• History of Malignant neoplasia in the last 2 years;
• Participation into other studies of cell therapy in the last year;
• Pregnancy or Breast-feeding.

Sponsors & Collaborators

• CellPraxis Bioengenharia Ltda.: lead
• Cryopraxis Criobiologia Ltda.: collaborator
• Federal University of São Paulo: collaborator
• University of South Florida: collaborator

Study Sites (1)

Federal University of São Paulo

São Paulo, São Paulo, SP, Brazil

Location

MeSH Terms

Conditions

Angina Pectoris

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Due to ethical aspects and the inability to justify the use of a surgical intramyocardial placebo in this population, this was non-randomized, open study.

Results Point of Contact

• Title: Dr. Nelson Americo Hossne Junior
• Organization: Federal University of Sao Paulo (UNIFESP)

nelson.hossne@gmail.com

+55 11 5571-2719

Study Officials

• Nelson A Hossne Junior, MD, PhD

  Federal University of São Paulo

  PRINCIPAL INVESTIGATOR

• Enio Buffolo, MD, PhD

  Federal University of São Paulo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2013
• First Posted: October 21, 2013
• Study Start: July 1, 2005
• Primary Completion: November 1, 2011
• Study Completion: December 1, 2012
• Last Updated: June 3, 2014
• Results First Posted: June 3, 2014

Record last verified: 2014-05

Locations

BR (1)