Combined CABG and Stem-Cell Transplantation for Heart Failure

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2008 by Helsinki University.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Helsinki University
ClinicalTrials.gov Identifier:
NCT00418418
First received: January 3, 2007
Last updated: August 18, 2008
Last verified: August 2008
  Purpose

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.


Condition Intervention Phase
Heart Failure
Myocardial Infarction
Coronary Artery Disease
Procedure: Coronary bypass operation
Procedure: Bone marrow aspiration (crista iliaca)
Biological: Intramyocardial mesenchymal stem cell transplantation
Biological: Intramyocardial injection of autologous serum
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Combined CABG and Stem-Cell Transplantation for Heart Failure

Resource links provided by NLM:


Further study details as provided by Helsinki University:

Primary Outcome Measures:
  • Does a bone marrow transplantation therapy increase the ejection fraction of the heart measured with MRI, when compared with placebo treatment? [ Time Frame: 1 year after the transplantation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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? [ Time Frame: 6 months and 1 year after the procedure ] [ Designated as safety issue: Yes ]
  • Does a bone marrow transplantation therapy improve BNP-value? [ Time Frame: 3kk, 6 months and 1 year after the procedure ] [ Designated as safety issue: Yes ]
  • Does a bone marrow transplantation therapy decrease hospitalization or the days stayed in hospital? [ Time Frame: primary hospital stay after the transplantation ] [ Designated as safety issue: No ]
  • Does pericardial fluid growth factor concentrations correlate to left ventricular function improvement? [ Time Frame: up to 1 year after the translantation ] [ Designated as safety issue: No ]
  • Does autologous cardiac stem cell quality correlate to left ventricular function improvement? [ Time Frame: 3kk, 6 months and 1 year after the transplantation ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: October 2006
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
Patient group receiving the stem cell injections during the CABG
Procedure: Coronary bypass operation
Coronary bypass operation is performed via sternotomy during cardiac arrest.
Other Name: CABG
Procedure: 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).
Other Name: Stem cell harvest
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)
Other Name: Stem cell therapy
Placebo Comparator: B
The patient group receiving autologous serum injections during the CAGB operation
Procedure: Coronary bypass operation
Coronary bypass operation is performed via sternotomy during cardiac arrest.
Other Name: CABG
Procedure: 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).
Other Name: Stem cell harvest
Biological: Intramyocardial injection of autologous serum
Intramyocardial injection of autologous serum is injected during cardiac arrest
Other Name: Stem cell control therapy

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00418418

Contacts
Contact: Ari Harjula, MD,PhD +3585064814 ari.harjula@hus.fi
Contact: Tommi Pätilä, MD +358504272291 tommi.patila@hus.fi

Locations
Finland
Department of Cardiothoracic Surgery, Meilahti Hospital Recruiting
Helsinki, Finland, 00029-HUS
Contact: Ari Harjula, MD, PhD    +5042764814    ari.harjula@hus.fi   
Contact: Tommi Pätilä, MD, PhD    +358504272291    tommi.patila@hus.fi   
Principal Investigator: Ari Harjula, MD, PhD         
Principal Investigator: Tommi Pätilä, MD         
Principal Investigator: Sinisalo Juha, MD, PhD         
Principal Investigator: Antti Vento, MD,PhD         
Sub-Investigator: Mika Laine, MD,PhD         
Sub-Investigator: Pekka Hämmäinen, MD, PhD         
Sub-Investigator: Esko Kankuri, MD, PhD         
Sub-Investigator: Reino Pöyhiä, MD, PhD         
Sub-Investigator: Raili Suojaranta-Ylinen, MD, PhD         
Sub-Investigator: Aapo Ahonen, MD, PhD         
Sub-Investigator: Jorma Sipponen, MD, PhD         
Sub-Investigator: Markku Kupari, MD, PhD         
Sub-Investigator: Riitta Alitalo, MD; PhD         
Sponsors and Collaborators
Helsinki University
Investigators
Principal Investigator: Ari Harjula, MD; PhD Department of Cardiothoracic Surgery, Helsinki University MeilahtiHospital
  More Information

Additional Information:
No publications provided by Helsinki University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Reijo Haapiainen, Helsinki University Hospital
ClinicalTrials.gov Identifier: NCT00418418     History of Changes
Other Study ID Numbers: TYH 6220
Study First Received: January 3, 2007
Last Updated: August 18, 2008
Health Authority: Finland: Ministry of Social Affairs and Health

Keywords provided by Helsinki University:
Cell transplantation
Heart failure
Clinical trials

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Failure
Infarction
Myocardial Infarction
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Ischemia
Pathologic Processes
Necrosis

ClinicalTrials.gov processed this record on July 29, 2014