UMIN-CTR Clinical Trial

Basic information
Public title	Ex Vivo Expanded Erythroblast-Transplantation for patient with critical limb ischemia
Acronym	EVEETA study
Scientific Title	Ex Vivo Expanded Erythroblast-Transplantation for patient with critical limb ischemia
Scientific Title:Acronym	EVEETA study
Region	Japan

Condition
Condition	Peripheral Arterial Disease (PAD) , Buerger disease, and arteritis associated with collagen diseases (Fontaines stage: III and IV)
Classification by specialty	Cardiology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To investigated the safety and efficacy of angiogenic cell therapy by implantation of ex vivo expanded immature erythroblasts cultured from autologous bone marrow cells for patient with critical limb ischemia
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	improvement of skin perfusion pressure level at ischemic leg 1 month after EVEETA
Key secondary outcomes

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Other
Interventions/Control_1	1)Autologous Bone Marrow Collection: 40 to 60 ml of bone marrow is collected from iliaccrest under local anaesthesia 14 days before the implantation. 2)Ex vivo expanded immature erythroblasts from autologous bone marrow cells : All procedures are enforced by exclusive technical exparts along the approved protocols in GMP-grade Cell Processing Room established in Bioscience Medical Research Center, Niigata University Medical and Dental Hospital. Mononuclear cells separated from the bone marrow are incubated in a suspension culture in the presence of rh Flt-ligand, rh SCF, rh Thrombopoietin, and culture supplements for 7 days to expand myeloid progenitors. Harvested and washed cells are further cultured in the presence of rh SCF, rh IGF-I, rh Erythropoietin, and culture supplements for additional 7 days to expand immature erythroblasts and macrophages. Cultured cells are finally harvested, washed, suspended in 50 ml of autologous platelet rich plasma, and transferred from the bio clean room to bedside. 3)Transplantation of cultured cell: Aliquots of the 50 ml of cell suspension are intramuscularly injected in 100 points of the ischaemic limb. Daily intramuscular injection of 6000 IU of rh erythropoietin in the same loci follows from day 0 for consecutive 5 days.
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

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	80 years-old >=
Gender	Male and Female
Key inclusion criteria	Peripheral Arterial Disease (PAD) , Buerger disease, and arteritis associated with collagen diseases 1. Fontaines stage: III and IV 2. Patient with critical limb ischemia, who were not candidates for endovascular treatment /surgical revascularisation, or skin perfusion pressure<40mmHg at ischemic leg even after endovascular treatment /surgical revascularisation 4. Age: greater than 20 or less than 80 years
Key exclusion criteria	1. Patients with the expected rest of their life less than 1 year 2. Patients with drug dependence during the past 3 months 3. Patients with malignant evidence of malignant disorder during the past 5 years 4. Patients with poorly controlled diabetes mellitus accompanied with proliferative retinopathy 5. Patients with polycythemia; Hematcrit >55%(male), >50%(female) 6. Patients without informed consent 7. Pregnant or possibly pregnant females 8. Patients with acute myocardial infarction, unstable angina, myocarditis, or cerebral infarction during the past 1 month 9. Patients with active infection including Treponema pallidum, or positive test for Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) 10. Patients with history of allergy for antibiotics 11. Patients with anemia or thrombocytopenia 12. Patients judged inappropriate for this study by phisician 13. Patients without agreement for including in this study
Target sample size	11

Research contact person
Name of lead principal investigator	1st name Tohru Middle name Last name Minamino
Organization	Niigata University Graduate School of Medical and Dental Sciences
Division name	Department of Cardiovascular Biology and Medicine
Zip code	9518510
Address	1-754 Asahimachi-Dori, Niigata, Japan
TEL	0252272185
Email	tminamino@med.niigata-u.ac.jp

Public contact
Name of contact person	1st name Takao Middle name Last name Yanagawa
Organization	Niigata University Graduate School of Medical and Dental Sciences
Division name	Department of Cardiovascular Biology and Medicine
Zip code	9518510
Address	1-754 Asahimachi-Dori, Niigata, Japan
TEL	0252272185
Homepage URL
Email	takao-ya@med.niigata-u.ac.jp

Sponsor
Institute	EVEETA Study Group
Institute
Department

Funding Source
Organization	JSPS KAKENHI Grant Numbers 15K09117
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Kyushu University Hospitals Specially Certified Committee for Regenerative Medicine
Address	3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, JAPAN
Tel	092-642-5774
Email	byskenkyu@jimu.kyushu-u.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2016 Year 03 Month 07 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
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

Progress
Recruitment status	Terminated
Date of protocol fixation	2015 Year 08 Month 20 Day
Date of IRB	2016 Year 01 Month 28 Day
Anticipated trial start date	2016 Year 03 Month 07 Day
Last follow-up date	2020 Year 06 Month 30 Day
Date of closure to data entry	2020 Year 06 Month 30 Day
Date trial data considered complete	2020 Year 06 Month 30 Day
Date analysis concluded	2020 Year 06 Month 30 Day

Other
Other related information

Management information
Registered date	2016 Year 03 Month 07 Day
Last modified on	2021 Year 09 Month 23 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000024652