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

Primary Purpose

Congestive Heart Failure, Ischemic Cardiomyopathy, Ventricular Dysfunction

Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
human cardiac stem cells
Sponsored by
Naofumi Takehara
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Congestive Heart Failure focused on measuring ischemic cardiomyopathy (ICM)

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Kyoto Prefectural University School of Medicine
  • National Cardiovascular Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

human cardiac stem cell therapy

Arm Description

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)

Outcomes

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.

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.

Full Information

First Posted
September 19, 2009
Last Updated
March 31, 2015
Sponsor
Naofumi Takehara
Collaborators
National Cerebral and Cardiovascular Center, Japan, Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan, Asahikawa Medical College
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1. Study Identification

Unique Protocol Identification Number
NCT00981006
Brief Title
AutoLogous Human CArdiac-Derived Stem Cell to Treat Ischemic cArdiomyopathy (ALCADIA)
Acronym
ALCADIA
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Naofumi Takehara
Collaborators
National Cerebral and Cardiovascular Center, Japan, Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan, Asahikawa Medical College

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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%).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congestive Heart Failure, Ischemic Cardiomyopathy, Ventricular Dysfunction
Keywords
ischemic cardiomyopathy (ICM)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
human cardiac stem cell therapy
Arm Type
Experimental
Arm Description
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)
Intervention Type
Procedure
Intervention Name(s)
human cardiac stem cells
Other Intervention Name(s)
human cardiac stem cell (hCSC), human recombinant basic fibroblast growth factor (bFGF), coronary artery bypass grafting (CABG)
Intervention Description
Single intramyocardial Injection of autologous hCSCs : 20 cites of infarcted myocardium Implantation of gelatin hydrogel sheet incorporating bFGF: 200 microgram. CABG surgery.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Clinical diagnosis of ischemic cardiomyopathy Ischemic cardiomyopathy with old myocardial infarction due to coronary artery atherosclerotic disease. Age: 20 to 80 years old left ventricle (LV) dysfunction : An ejection fraction (EF)≧15%, and ≦35% assessed by echocardiography Refractory heart failure: American Heart Association (AHA)/American College of Cardiology (ACC)heart failure Stage D Heart failure symptom: New York Heart Association (NYHA) Class III or IV An indication for CABG:A myocardial ischemia according to major coronary artery stenosis (>75%) 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. written informed consent Exclusion Criteria: New onset of myocardial infarction or unstable angina within 28 days prior to study entry Indication for surgical ventricular reconstruction or mitral valve repair *1 Contraindication for endomyocardial biopsy *2 Evidence for malignant disease within 3 years prior to study entry Chronic hemodialysis Liver Cirrhosis (ICGR 15 >30%) Uncontrollable diabetes mellitus (HbA1c>8.0) Maximum diameter of Aortic aneurysm more than 5.5 cm.(including dissecting aneurysm) Cardiogenic shock Active infection (including cytomegalovirus infection) Drug or alcoholic dependency Positive for HIV antigen Active bleeding state (gastric ulcer, cerebral bleeding, etc.) Gelatin allergy *3 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hiroaki Matsubara, MD,PhD
Organizational Affiliation
Kyoto Prefectural University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kyoto Prefectural University School of Medicine
City
Kyoto
State/Province
Kajii-cho 465, hirokoji-agaru, kawaramachi-dori,kamikyoku
ZIP/Postal Code
602-8566
Country
Japan
Facility Name
National Cardiovascular Center
City
Osaka
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
19038683
Citation
Takehara N, Tsutsumi Y, Tateishi K, Ogata T, Tanaka H, Ueyama T, Takahashi T, Takamatsu T, Fukushima M, Komeda M, Yamagishi M, Yaku H, Tabata Y, Matsubara H, Oh H. Controlled delivery of basic fibroblast growth factor promotes human cardiosphere-derived cell engraftment to enhance cardiac repair for chronic myocardial infarction. J Am Coll Cardiol. 2008 Dec 2;52(23):1858-1865. doi: 10.1016/j.jacc.2008.06.052.
Results Reference
background
PubMed Identifier
17502484
Citation
Tateishi K, Ashihara E, Takehara N, Nomura T, Honsho S, Nakagami T, Morikawa S, Takahashi T, Ueyama T, Matsubara H, Oh H. Clonally amplified cardiac stem cells are regulated by Sca-1 signaling for efficient cardiovascular regeneration. J Cell Sci. 2007 May 15;120(Pt 10):1791-800. doi: 10.1242/jcs.006122.
Results Reference
background
PubMed Identifier
17150190
Citation
Tateishi K, Ashihara E, Honsho S, Takehara N, Nomura T, Takahashi T, Ueyama T, Yamagishi M, Yaku H, Matsubara H, Oh H. Human cardiac stem cells exhibit mesenchymal features and are maintained through Akt/GSK-3beta signaling. Biochem Biophys Res Commun. 2007 Jan 19;352(3):635-41. doi: 10.1016/j.bbrc.2006.11.096. Epub 2006 Nov 27.
Results Reference
background
PubMed Identifier
24444305
Citation
Chimenti I, Gaetani R, Forte E, Angelini F, De Falco E, Zoccai GB, Messina E, Frati G, Giacomello A. Serum and supplement optimization for EU GMP-compliance in cardiospheres cell culture. J Cell Mol Med. 2014 Apr;18(4):624-34. doi: 10.1111/jcmm.12210. Epub 2014 Jan 20.
Results Reference
derived
Links:
URL
http://www.f.kpu-m.ac.jp/k/med2/index.html
Description
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AutoLogous Human CArdiac-Derived Stem Cell to Treat Ischemic cArdiomyopathy (ALCADIA)

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