Congestive Heart FailurePhase 1ALCADIANCT00981006
AutoLogous Human CArdiac-Derived Stem Cell to Treat Ischemic cArdiomyopathy (ALCADIA)
A Phase 1 study testing human cardiac stem cells in people with Congestive Heart Failure and Ischemic Cardiomyopathy, run by Naofumi Takehara at 2 sites in Japan.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Congestive Heart Failure, Ischemic Cardiomyopathy, Ventricular Dysfunction
- What is being tested?
- human cardiac stem cells
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesJapan
- Study dates
- Apr 2010to Mar 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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%)
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- 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.
Trial locations and contacts
2 sites in 1 country.
Japan2 sites
Kyoto Prefectural University School of Medicine
Kyoto, Kajii-cho 465, Hirokoji-agaru, Kawaramachi-dori,kamikyoku, 602-8566
National Cardiovascular Center
Osaka
About this study
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
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%).
Read the 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.
- Being tested
- human cardiac stem cells
- Keywords
- ischemic cardiomyopathy (ICM)
- Medical subject headings
- Heart Failure, Ventricular Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
human cardiac stem cellsProcedure or surgery
Also called human cardiac stem cell (hCSC), human recombinant basic fibroblast growth factor (bFGF), coronary artery bypass grafting (CABG)
Single intramyocardial Injection of autologous hCSCs : 20 cites of infarcted myocardium Implantation of gelatin hydrogel sheet incorporating bFGF: 200 microgram. CABG surgery.
| Study group | Role | What they receive |
|---|---|---|
| human cardiac stem cell therapy | Experimental | 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) Receives: Procedure: human cardiac stem cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 month
Secondary outcomes (1)
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.
Measured: 12month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2009 (estimated)
- Study startApr 2010
- Primary completionMar 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Congestive Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Naofumi Takehara
- Sponsor type
- University, hospital or other
- Collaborators
- National Cerebral and Cardiovascular Center, Japan, Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan, Asahikawa Medical College
- Responsible party
- Sponsor-investigator, Naofumi Takehara, Kyoto Prefectural University of Medicine
- Investigators
- Hiroaki Matsubara, MD,PhD, Principal investigator, Kyoto Prefectural University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00981006
- Sponsor's protocol ID
- TRICAD0910
- Other IDs
- TRICAD0806
- Acronym
- ALCADIA
- Status last verified
- Mar 2015
- First submitted
- 19 Sep 2009
- Last updated
- 1 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 19038683Tateishi 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.
PubMed 17502484Tateishi 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.
PubMed 17150190Chimenti 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.
PubMed 24444305
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00981006
- Acronym / sponsor ID
- ALCADIA / TRICAD0910
- Keywords
- ischemic cardiomyopathy (ICM)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Naofumi TakeharaUniversity, hospital or other
- Collaborators
- National Cerebral and Cardiovascular Center, Japan, Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan, Asahikawa Medical College
- Study start
- Apr 2010
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 21 Sep 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| human cardiac stem cell therapy | Experimental | Procedure: human cardiac stem cellssingle 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) |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Clinical diagnosis of ischemic cardiomyopathy
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| human cardiac stem cellsAlso: human cardiac stem cell (hCSC), human recombinant basic fibroblast growth factor (bFGF), coronary artery bypass grafting (CABG)Single intramyocardial Injection of autologous hCSCs : 20 cites of infarcted myocardium Implantation of gelatin hydrogel sheet incorporating bFGF: 200 microgram. CABG surgery. | Procedure or surgery | human cardiac stem cell therapy |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2015.
- Background: PubMed 19038683Takehara 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.
- Background: PubMed 17502484Tateishi 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.
- Background: PubMed 17150190Tateishi 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.
- Derived from this study: PubMed 24444305Chimenti 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.
- Click here for more information about this studyLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hiroaki Matsubara, MD,PhD principal investigator
Kyoto Prefectural University School of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing human cardiac stem cells in people with Congestive Heart Failure and Ischemic Cardiomyopathy, run by Naofumi Takehara at 2 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00981006, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2015.