- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00981006
AutoLogous Human CArdiac-Derived Stem Cell to Treat Ischemic cArdiomyopathy (ALCADIA) (ALCADIA)
March 31, 2015 updated by: Naofumi Takehara
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
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%).
Study Overview
Status
Completed
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
6
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Osaka, Japan
- National Cardiovascular Center
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Kajii-cho 465, hirokoji-agaru, kawaramachi-dori,kamikyoku
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Kyoto, Kajii-cho 465, hirokoji-agaru, kawaramachi-dori,kamikyoku, Japan, 602-8566
- Kyoto Prefectural University School of Medicine
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
20 years to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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)
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Single intramyocardial Injection of autologous hCSCs : 20 cites of infarcted myocardium Implantation of gelatin hydrogel sheet incorporating bFGF: 200 microgram.
CABG surgery.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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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
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12 month
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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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
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12month
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Hiroaki Matsubara, MD,PhD, Kyoto Prefectural University School of Medicine
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
- 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.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2010
Primary Completion (Actual)
March 1, 2013
Study Completion (Actual)
March 1, 2013
Study Registration Dates
First Submitted
September 19, 2009
First Submitted That Met QC Criteria
September 19, 2009
First Posted (Estimate)
September 21, 2009
Study Record Updates
Last Update Posted (Estimate)
April 1, 2015
Last Update Submitted That Met QC Criteria
March 31, 2015
Last Verified
March 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- TRICAD0910
- TRICAD0806 (Registry Identifier: TRI)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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