UMIN-CTR Clinical Trial

Public 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

Acronym

AutoLogous human CArdiac-Derived stem cell to treat Ischemic cArdiomyopathy
(ALCADIA)

Scientific 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

Scientific Title:Acronym

AutoLogous human CArdiac-Derived stem cell to treat Ischemic cArdiomyopathy
(ALCADIA)

Region

Japan

Condition

severe refractory heart failure with chronic ischemic cardiomyopathy

Classification by specialty

Cardiology

Cardiovascular surgery

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

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

Basic objectives2

Safety

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase I

Primary outcomes

Safety
1. major adverse cardiac event (MACE)
(cardiovascular death, sustained ventricular arrhythmia, re-hospitalization for heart failure, new onset of acute cardiovascular syndrome, or cardiac tamponade which needs surgical repair)
2. serious adverse events without major adverse cardiac event
3. adverse event

Key secondary outcomes

Efficacy
1. New York Heart Association (NYHA) class
2. Left ventricular ejection fraction (LVEF) as assessed by the bi-planar modified Simpson method
3. regional wall motion score in infarct area by cardiac MRI
4. infarct volume evaluated by cardiac MRI with late Gd-enhancement

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Historical

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

1. Injection of autologous human cardiac stem cell.
Before proceeding with the trial, the isolated and cultured cardiac stem cell will need to reach a target of 5 x 10e5 cells/kg. Once the target number is achieved and quality is satisfactory during the procedure the stem cells will be injected intra-myocardially on the target site of the heart at 20 sites.
2. Implantation of gelatin hydrogel sheet incorporating bFGF.
All patients will receive an implantation of the controlled release of human recombinant basic fibroblast growth factor (bFGF) (200microgram) using a biodegradable gelatin hydrogel sheet.
3. CABG Surgery.
These procedure will be administered following completion of CABG surgery. The number of grafts will depend on the findings of the pre-operative angiogram.
4. Observation period; 1 year after surgery

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

80

years-old

>=

Gender

Male and Female

Key inclusion criteria

1) Age: 20 to 80 years old
2) LV function: An ejection fraction (EF)>15%, and <35%
3) AHA/ACC stage: Stage D
4) NYHA: Class III or IV
5) An indication for CABG
A myocardial ischemia according to major coronary artery stenosis(>75%)
6) Viability in the infarct area:
as measured by cardiac delayed hyperenhancement magnetic resonance imaging (MRI)
1. Infarct area affecting>2 contiguous LV segments in a 18-segment model
2. The number of segments which transmural extent of hyperenhancment 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
7) written informed consent

Key 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 5cm(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
1 cardiogenic shock
2 end-stage or uncontrollable congestive heart
failure without continues infusion of
catecholamine
3 complete or mobitz type AV block
*3 The screening of gelatin allergy is necessary for all patients by gelatin patch test and gelatin-IgE

Target sample size

6

Name of lead principal investigator

1st name
Middle name
Last name	Hiroaki Matsubara

Organization

Kyoto Prefectural University School of Medicine

Division name

The Department of Cardiovascular medicine

Zip code

Address

602-8566 Kajii-cho 465, hirokoji-agaru, kawaramachi-dori,kamikyoku, Kyoto,Japan

TEL

075-251-5111

Email

matsubah@koto.kpu-m.ac.jp

Name of contact person

1st name
Middle name
Last name	Hiroaki Matsubara

Organization

Kyoto Prefectural University School of Medicine

Division name

The Department of Cardiovascular medicine

Zip code

Address

602-8566 Kajii-cho 465, hirokoji-agaru, kawaramachi-dori,kamikyoku, Kyoto,Japan

TEL

075-251-5111

Homepage URL

http://www.f.kpu-m.ac.jp/k/med2/index.html

Email

matsubah@koto.kpu-m.ac.jp

Institute

Kyoto Prefectural University School of Medicine

Institute

Department

Personal name

Organization

The Ministry of Health, Labour, and Welfare

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan

Co-sponsor

The National Cardiovascular Center

Translational Research Informatics Centre,
Foundation for Biomedical Research and Innovation,

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

京都府立医科大学付属病院
国立循環器病センター

Date of disclosure of the study information

2009

Year

10

Month

01

Day

URL releasing protocol

http://www.f.kpu-m.ac.jp/k/med2/index.html

Publication of results

Partially published

URL related to results and publications

http://www.f.kpu-m.ac.jp/k/med2/index.html

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2009

Year

09

Month

10

Day

Date of IRB

Anticipated trial start date

2009

Year

10

Month

01

Day

Last follow-up date

2012

Year

10

Month

01

Day

Date of closure to data entry

2012

Year

10

Month

01

Day

Date trial data considered complete

2013

Year

03

Month

21

Day

Date analysis concluded

2013

Year

03

Month

31

Day

Other related information

Registered date

2009

Year

09

Month

17

Day

Last modified on

2014

Year

03

Month

17

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000003081