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AutoLogous Human CArdiac-Derived Stem Cell to Treat Ischemic cArdiomyopathy (ALCADIA)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
National Cerebral and Cardiovascular Center
Translational Research Informatics Center, Kobe, Hyogo, Japan
Asahikawa Medical College
Information provided by (Responsible Party):
Naofumi Takehara, Kyoto Prefectural University of Medicine
ClinicalTrials.gov Identifier:
NCT00981006
First received: September 19, 2009
Last updated: February 7, 2013
Last verified: February 2013
  Purpose

The aim of this study is to evaluate the safety and efficacy on the transplantation of autologous human cardiac-derived stem cells (hCSCs) with the controlled release of basic fibroblast growth factor (bFGF) to severe refractory heart failure patients with chronic ischemic cardiomyopathy concordance with reduced left ventricular dysfunction (15%≦LVEF≦35%).


Condition Intervention Phase
Congestive Heart Failure
Ischemic Cardiomyopathy
Ventricular Dysfunction
Procedure: human cardiac stem cells
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Hybrid Biotherapy Involving Autologous Human Cardiac Stem Cell Transplantation Combined With the Controlled Release of bFGF Using a Gelatin Hydrogel Sheet to Treat Severe Refractory Heart Failure With Chronic Ischemic Cardiomyopathy

Resource links provided by NLM:


Further study details as provided by Kyoto Prefectural University of Medicine:

Primary Outcome Measures:
  • The primary objective is to evaluate the safety of autologous cardiac-derived stem cells administered by intra-myocardial injection with the controlled release of bFGF in severe refractory heart failure patients with chronic ischemic cardiomyopathy. [ Time Frame: 12 month ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The secondary objective is to demonstrate the safety of autologous cardiac-derived stem cells administered by intra-myocardial injection with the controlled release of bFGF in severe refractory heart failure patients with chronic ischemic cardiomyopathy. [ Time Frame: 12month ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 6
Study Start Date: April 2010
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: human cardiac stem cell therapy
single administration of 0.5 million cells/kg(patient body weight) of human cardiac stem cells and 200 microgram of bFGF at coronary artery bypass grafting (CABG)
Procedure: human cardiac stem cells
Single intramyocardial Injection of autologous hCSCs : 20 cites of infarcted myocardium Implantation of gelatin hydrogel sheet incorporating bFGF: 200 microgram. CABG surgery.
Other Names:
  • human cardiac stem cell (hCSC)
  • human recombinant basic fibroblast growth factor (bFGF)
  • coronary artery bypass grafting (CABG)

Detailed Description:

Autologous human stem or progenitor cells of different lineage have been subjected to clinical trials in the past to treat patients with ischemic cardiomyopathy. Although human stem or progenitor cells transplantation had functional benefits in the recovery in experimental myocardial infarction, the major barrier limiting its clinical application is the death of the most of the transplanted cells and poor cardiac differentiation in the host environment. Using the identical technique as clonally cell isolation from experimental animals, we generated human cardiac-derived stem cell (hCSC) enriched Es-marker genes with mesenchymal features. hCSCs included in cell populations accelerating proliferation in the presence of basic fibroblast growth factor (bFGF) on plastic plates are generated from human heart tissues through endomyocardial biopsy. Giving a patient their own hCSCs is an investigational procedure that has been approved by the committee of the Ministry of Health, Labour, and Welfare of Japan for this study. hCSCs have excellent potential to proliferate and regenerate to cardiomyocyte compared with other cells, e.g. myoblasts, bone marrow mononuclear cells and bone marrow stem cells, already evaluated in preliminary experiments on the repair of injured heart muscle. bFGF possesses properties to promote stem cell proliferation, and formation of sufficient microvascular network created by bFGF is critical for long-term survival of transplanted donor cells. This will be the first trial on the use of autologous hCSCs for the treatment of refractory heart failure with chronic ischemic cardiomyopathy. This trial is translational pilot study for looking into the safety and efficacy on the use of autologous hCSCs with the controlled release of bFGF using a gelatin hydrogel sheet.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Clinical diagnosis of ischemic cardiomyopathy

    • Ischemic cardiomyopathy with old myocardial infarction due to coronary artery atherosclerotic disease.
  2. Age: 20 to 80 years old
  3. left ventricle (LV) dysfunction : An ejection fraction (EF)≧15%, and ≦35% assessed by echocardiography
  4. Refractory heart failure: American Heart Association (AHA)/American College of Cardiology (ACC)heart failure Stage D
  5. Heart failure symptom: New York Heart Association (NYHA) Class III or IV
  6. An indication for CABG:A myocardial ischemia according to major coronary artery stenosis (>75%)
  7. Viability in the infarct area as measured by cardiac delayed hyperenhancement magnetic resonance imaging (MRI)

    • Infarct area affecting >2 contiguous LV segments in a 18-segment model
    • The number of segments which transmural extent of hyperenhancement more than 51% is less than one.

      • Ex1. infarct area with or without bypass graft.
      • Ex2. no correlation with graft number.
      • Ex3. in case of multiple myocardial infarction, an indication for larger in infarct volume.
  8. written informed consent

Exclusion Criteria:

  1. New onset of myocardial infarction or unstable angina within 28 days prior to study entry
  2. Indication for surgical ventricular reconstruction or mitral valve repair *1
  3. Contraindication for endomyocardial biopsy *2
  4. Evidence for malignant disease within 3 years prior to study entry
  5. Chronic hemodialysis
  6. Liver Cirrhosis (ICGR 15 >30%)
  7. Uncontrollable diabetes mellitus (HbA1c>8.0)
  8. Maximum diameter of Aortic aneurysm more than 5.5 cm.(including dissecting aneurysm)
  9. Cardiogenic shock
  10. Active infection (including cytomegalovirus infection)
  11. Drug or alcoholic dependency
  12. Positive for HIV antigen
  13. Active bleeding state (gastric ulcer, cerebral bleeding, etc.)
  14. Gelatin allergy *3
  15. Chromosomal abnormality

    • 1 an indication for LV aneurysmectomy; patients with over 2 segments of dyskinesis area
    • 2 contra-indication for endomyocardial biopsy

      • cardiogenic shock
      • end-stage or uncontrollable congestive heart failure without continues infusion of catecholamine
      • complete or mobitz type atria-ventricular block
    • 3 The screening of gelatin allergy is necessary for all patients by gelatin patch test and gelatin-immunoglobulin E.
  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: NCT00981006

Locations
Japan
Kyoto Prefectural University School of Medicine
Kyoto, Kajii-cho 465, hirokoji-agaru, kawaramachi-dori,kamikyoku, Japan, 602-8566
National Cardiovascular Center
Osaka, Japan
Sponsors and Collaborators
Naofumi Takehara
National Cerebral and Cardiovascular Center
Translational Research Informatics Center, Kobe, Hyogo, Japan
Asahikawa Medical College
Investigators
Principal Investigator: Hiroaki Matsubara, MD,PhD Kyoto Prefectural University School of Medicine
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Naofumi Takehara, Assistant Professor, Kyoto Prefectural University of Medicine
ClinicalTrials.gov Identifier: NCT00981006     History of Changes
Obsolete Identifiers: NCT01697033
Other Study ID Numbers: TRICAD0910, TRICAD0806
Study First Received: September 19, 2009
Last Updated: February 7, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Kyoto Prefectural University of Medicine:
ischemic cardiomyopathy (ICM)

Additional relevant MeSH terms:
Cardiomyopathies
Heart Failure
Ischemia
Ventricular Dysfunction
Cardiovascular Diseases
Heart Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on November 25, 2014