Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01966042
Recruitment Status : Completed
First Posted : October 21, 2013
Results First Posted : June 3, 2014
Last Update Posted : June 3, 2014
Sponsor:
Collaborators:
Cryopraxis Criobiologia Ltda.
Federal University of São Paulo
University of South Florida
Information provided by (Responsible Party):
CellPraxis Bioengenharia Ltda.

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.


Condition or disease Intervention/treatment Phase
Refractory Angina Procedure: Local sedation Procedure: Bone Marrow Aspiration Procedure: Minithoracotomy Biological: Autologous bone marrow mononuclear cells infusion Phase 2

Detailed Description:

This was a phase II, non-controlled (single arm) and open label clinical trial. The study was approved by the Institutional Review Board (IRB) and all patients gave informed consent prior to participation.

Refractory angina patients were defined as those with functional class IV (angina at rest) according to the Canadian Cardiovascular Society Angina Classification (CCSAC) despite maximum medical therapy, not suitable for conventional myocardial revascularization and viable myocardium confirmed by nuclear imaging.

Patients were evaluated according to different parameters, for a total period of 12 months, and the primary objectives were:

  1. Improvement in functional class and angina symptoms (CCSAC) of the patients with refractory angina pectoris after the infusion of autologous bone marrow mononuclear cells after the intervention;
  2. Improvement in myocardial perfusion before and after cell delivery;
  3. Evaluate the safety of the delivery of autologous bone marrow mononuclear cells route in individuals with refractory angina.

In the screening evaluation, individuals with the presumptive diagnosis of class IV refractory angina and who met all study criteria were approached about the possibility of participating in the study by the principal investigator. Then, the patients were submitted to a baseline evaluation with a serious of blood and image tests.

The interventions were the Bone Marrow Aspiration - For each patient, a total of 100 cc of bone marrow was aspirated from the iliac crest at the time of anesthesia for their cardiac surgery - and the Infusion - After processing the cells, the surgeon delivered it by a series of epicardial injections into the left ventricular myocardium.

The processing of bone marrow autologous cells aimed to enrich the content of the bone marrow aspirate, separating the mononuclear fraction from the cells which were already differentiated.

The postoperative stage was conducted in an identical way to that of patients who undergo to a myocardial revascularization surgery. It is important to mention that both the ICU and the ward time varied according to the patient's individual evolution.

Finally, the first follow up visit took place at 1 month after the surgery. The subsequent visits were held at 3, 6 and 12 months after the procedure.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Intramyocardial Injection of Autologous Bone Marrow Stem Cells for Refractory Angina in Patients With Normal or Slightly Reduced Left Ventricular Function.
Study Start Date : July 2005
Actual Primary Completion Date : November 2011
Actual Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Angina

Arm Intervention/treatment
Experimental: Stem Cell Therapy

All subjects enrolled in the study underwent:

Local Sedation; Bone Marrow Aspiration; Minithoracotomy; Autologous bone marrow mononuclear cells infusion.

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

Procedure: Bone Marrow Aspiration
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.

Procedure: Minithoracotomy
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.

Biological: Autologous bone marrow mononuclear cells infusion
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.




Primary Outcome Measures :
  1. Angina Class Variation [ Time Frame: 3, 6 and 12 months ]

    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.



Secondary Outcome Measures :
  1. Functional Change Evaluation [ Time Frame: Baseline and 12 months ]
    Analysis of Left Ventricular Ejection Fraction (in %), by echocardiogram.

  2. Functional Change Evaluation [ Time Frame: Baseline, 6 and 12 months ]
    Analysis of objective improvement in myocardial ischemia (in %), by stress technetium scintigraphy.


Other Outcome Measures:
  1. Life Quality [ Time Frame: Baseline and 12 months ]

    Analysis of the variation in life quality questionnaire - Short Form Health Survey (SF-36) was performed. Each domain of the questionnaire was evaluated as a quantitative variable and the medians were retrieved before and after the procedure.

    The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index.

    It consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e. a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

    One patient was lost before answering the questionnaire post procedure.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

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): NCT01966042


Locations
Layout table for location information
Brazil
Federal University of São Paulo
São Paulo, Brazil, SP
Sponsors and Collaborators
CellPraxis Bioengenharia Ltda.
Cryopraxis Criobiologia Ltda.
Federal University of São Paulo
University of South Florida
Investigators
Layout table for investigator information
Principal Investigator: Nelson A Hossne Junior, MD, PhD Federal University of São Paulo
Study Director: Enio Buffolo, MD, PhD Federal University of São Paulo

Layout table for additonal information
Responsible Party: CellPraxis Bioengenharia Ltda.
ClinicalTrials.gov Identifier: NCT01966042     History of Changes
Other Study ID Numbers: Cell 0314/05
0314/05 ( Other Identifier: CEP )
First Posted: October 21, 2013    Key Record Dates
Results First Posted: June 3, 2014
Last Update Posted: June 3, 2014
Last Verified: May 2014

Keywords provided by CellPraxis Bioengenharia Ltda.:
Refractory angina
Cell Therapy
Bone Marrow
Mononuclear Cells

Additional relevant MeSH terms:
Layout table for MeSH terms
Angina Pectoris
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Neurologic Manifestations
Signs and Symptoms