Combined CABG and Stem-Cell Transplantation for Heart Failure

Coronary Artery Disease Clinical Trial

Official title:

Combined CABG and Stem-Cell Transplantation for Heart Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00418418
• Other study ID #: TYH 6220
• Status: Recruiting
• Phase: Phase 2
• First received: January 3, 2007
• Last updated: August 18, 2008
• Start date: October 2006
• Est. completion date: December 2010

Study information

• Verified date: August 2008
• Source: Helsinki University
• Contact: Ari Harjula, MD,PhD
• Phone: +3585064814
• Email: ari.harjula[@]hus.fi
• Is FDA regulated: No
• Health authority: Finland: Ministry of Social Affairs and Health
• Study type: Interventional

Clinical Trial Summary

This is a prospective double blind trial of intraoperative transmyocardial bone marrow−derived mesenchymal cell transplantation vs placebo in patients with low left ventricular ejection fraction scheduled to coronary bypass operation.

Description:

The prevalence of symptomatic heart failure in general population is up to 2% and the prevalence increases rapidly with age. Half of the patients with symptomatic heart failure will die within 4 years of diagnosis.The purpose of this study is to examine the effect of bone marrow-derived stem cell transplantation in left ventricular ejection fraction.

Consecutive patients with systolic heart failure (n=60), with ischemic coronary heart disease, scheduled to by-pass-operation (CABG) will be collected from cardiovascular laboratory and outpatient clinic of Helsinki University Central Hospital. Patients should have heart failure with ejection fraction between 15 to 45%. Randomly patients are selected to receive a stem cell transplantation with best possible heart failure medication, or without cell transplantation. In this study, 30 patients are receiving bone marrow transplantation, and 30 patients are serving as a control population. All patients will receive CABG.The study will be carried out with randomized, double blind techniques for one year. Randomization (in blocks) will be based on a table of random numbers.Bone marrow and patients own serum will be blinded by using colored syringe, so that the doctor transfusing the sample, will not be able to know the nature of the sample. From all patients, a right atrial biopsy will be collected for assessment of autologous cardiac stem cells. Also sample of pericardial fluid will be collected for measures of growth factors.

Comparisons: Preoperatively, patients will be imagined by cardiac ultrasound, cardiac MRI, cardiac PET and SPECT. Serum pro-BNB samples will be collected. Postoperatively at 3 months and 6 months pro-BNB and cardiac ultrasound will be evaluated. At one year cardiac ultrasound, cardiac MRI, cardiac PET and SPECT will be reassessed.

Heart failure and coronary artery disease treatments beside the transplantation will be optimized according to the judgment of the doctors of the outpatients clinic. Primary endpoint of the study is the change of ejection fraction in MRI images.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• General (patients must have all)

• Symptomatic heart failure.

• Scheduled to CABG

• Be 18 to 75 years of age

• Informed Consent obtained

• Heart Failure Presentation

• Patients of either gender, who has evaluated in cardiovascular laboratory and scheduled to CABG with moderate heart failure, will be eligible

• NYHA II-IV symptoms

• Left ventricular ejection fraction in screening echocardiography 15 to 45%.

• Optimal heart failure medication and coronary medication before operation, containing at least two heart failure drugs: must have ACE-inhibitor, or AT II blocker, and/or b-blocker together with diuretics, digitalis or aldosterone antagonist, and coronary medication: a statin and anticoagulation, either aspirin or clopidogrel.

Exclusion Criteria:

• Heart failure due to left ventricular outflow track obstruction (valve problem or HOCM)

• History of life-threatening ventricular arrhythmias or resuscitation, condition which may be repeatable or implanted ICD.

• Stroke or other disabling condition with in 3 months before screening

• Contraindications to coronary angiogram or MRI

• Other serious disease limiting life expectancy

• Participation in an other clinical trial

• Severe valve disease: mitral, aortic, tricuspid or pulmonic stenosis / insufficiency

• Scheduled valve operation

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Heart Failure
• Myocardial Infarction
• Myocardial Ischemia

Intervention

Procedure:
• Coronary bypass operation
Coronary bypass operation is performed via sternotomy during cardiac arrest.
• Bone marrow aspiration (crista iliaca)
The bone marrow is aspirated from the iliac crest (100ml). During the operation the aspirate is transported to the stem cell laboratory, where the sample is centrifugated through Ficoll(Registered Trademark).

Biological:
• Intramyocardial mesenchymal stem cell transplantation
During the cardiac arrest, stem cells are directly injected to myocardium. The amount of the cells varies individually (5-1000 x 10e6 cells), the cells are diluted in autologous serum (5 ml)
• Intramyocardial injection of autologous serum
Intramyocardial injection of autologous serum is injected during cardiac arrest

Locations

Country	Name	City	State
Finland	Department of Cardiothoracic Surgery, Meilahti Hospital	Helsinki

Sponsors (1)

Lead Sponsor	Collaborator
Helsinki University

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Does a bone marrow transplantation therapy increase the ejection fraction of the heart measured with MRI, when compared with placebo treatment?		1 year after the transplantation	Yes
Secondary	Does a bone marrow transplantation therapy increase any cardiac function parameter measured by a an echocardiography, MRI or PET ischemia area, when compared with no treatment group?		6 months and 1 year after the procedure	Yes
Secondary	Does a bone marrow transplantation therapy improve BNP-value?		3kk, 6 months and 1 year after the procedure	Yes
Secondary	Does a bone marrow transplantation therapy decrease hospitalization or the days stayed in hospital?		primary hospital stay after the transplantation	No
Secondary	Does pericardial fluid growth factor concentrations correlate to left ventricular function improvement?		up to 1 year after the translantation	No
Secondary	Does autologous cardiac stem cell quality correlate to left ventricular function improvement?		3kk, 6 months and 1 year after the transplantation	No

External Links

•   The Registry of Helsinki and Uusimaa Hospital District