UMIN-CTR Clinical Trial

Basic information
Public title	Research on Advanced Intervention using Novel Bone marrOW stem cell (RAINBOW): Phase I, open-label, uncontrolled, dose-response trial of autologous bone marrow stromal cell transplantation in patients with acute ischemic stroke
Acronym	RAINBOW trial
Scientific Title	Research on Advanced Intervention using Novel Bone marrOW stem cell (RAINBOW): Phase I, open-label, uncontrolled, dose-response trial of autologous bone marrow stromal cell transplantation in patients with acute ischemic stroke
Scientific Title:Acronym	RAINBOW trial
Region	Japan

Condition
Condition	acute ischemic stroke
Classification by specialty	Neurosurgery
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	Safety and efficacy of HUNS001-01(BMSC) by stereotactic injection
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Safety of HUNS001-01 administration for 1 year after the intervention: frequency of Adverse Event (AE)
Key secondary outcomes	Safety of HUNS001-01 administration for 30 days after the intervention: frequency of Adverse Event (AE) Safety of bone marrow aspiration: frequency of Adverse Event (AE) Frequency of the defects of HUNS001-01 at manufacturing Improvement of stroke symptoms for 1 year after the intervention using the following assessment scales: National Institute of Health Stroke Scale (NIHSS) modified Rankin Scale (mRS) Functional Independence Measure (FIM) Barthel Index Fugl-Meyer Assessment Improvement in lesion volume assessed by MRI analysis for 1 year after the intervention Assessment of cell distribution using MRI Assessment of possible functional shift for 1 year after the intervention using FDG-PET and IMZ-SPECT

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Dose comparison
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Maneuver Other
Interventions/Control_1	On the day when HUNS001-01 is manufactured, the cell product will be administered to the subject. A dose of 2 x 10^7 cells (400 micro L) will be administered in the low-dose group. HUNS001-01 is implanted using MRI stereotactic technique to define the target sites in the normal white matter around the lesion. The number of target sites is one or two in the low-dose group, and two or three in the high-dose group. The subject has a one or two burr-hole craniotomy under local anesthesia and sedation. Using 2.1-mm outer diameter stereotactic cannula, 200 to 400 micro L of the product is injected over a period of 5 min at each site. The cannula is removed after 5 min after finishing the injection at each site. In the perioperative period, all subjects take fosphenytoin sodium hydrate to prevent epileptic seizure due to the procedure.
Interventions/Control_2	On the day when HUNS001-01 is manufactured, the cell product will be administered to the subject. A dose of 5 x 10^7 cells (1,000 micro L) will be administered in the high-dose group. HUNS001-01 is implanted using MRI stereotactic technique to define the target sites in the normal white matter around the lesion. The number of target sites is one or two in the low-dose group, and two or three in the high-dose group. The subject has a one or two burr-hole craniotomy under local anesthesia and sedation. Using 2.1-mm outer diameter stereotactic cannula, 200 to 500 micro L of the product is injected over a period of 5 min at each site. The cannula is removed after 5 min after finishing the injection at each site. In the perioperative period, all subjects take fosphenytoin sodium hydrate to prevent epileptic seizure due to the procedure.
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	First screening; 14 days after the onset of stroke 1) Male or female subjects between 20 and 79 years old 2) Informed consent within 14 days after the onset 3) Clinical diagnosis of cerebral ischemic stroke on the internal carotid arterial region 4) Subjects with 0 or 1 in modified Rankin Scale (mRS) before the onset 5) Subjects who can have an informed consent; if insufficiently, legal representative is needed 6) Subjects with moderate or severe neurological symptoms; National Institute of Health Stroke Scale (NIHSS) more than 6, (however, the partial score in both `5. Motor Arm' and `6. Motor Leg' are more than 6) Second screening; 7 days before the administration 1) HUNS001-01 is available within 74 days after the onset 2) Subjects with moderate or severe neurological deficit; mRS>=3
Key exclusion criteria	First screening 1) Occurrence of a severe hemorrhagic transformation of ischemic stroke 2) Subjects with deep coma or coma evaluated by Japan Coma Scale (JCS; 300 or 200) 3) Severe anemia (hemoglobin<10.0 g/dL) or thrombocytopenia (platelet count <100,000/mm^3) 4) Severe heart disease (e.g. ischemic heart disease, heart failure) 5) Significant abnormal laboratory tests; a. >3 x ULN for alanine aminotransferase or aspartate aminotransferase b. >1.5 x ULN for total bilirubin c. >1.5 x ULN for serum creatinine 6) Uncontrolled hypertension, despite antihypertensive therapy 7) History of malignancy of any type 8) Carriers of infectious disease as follows: Syphilis, hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV)-1/2, human T cell leukemia virus (HTLV)-1, or parvovirus B19 9) Subjects who are during pregnancy or want to have children 10) Lactating women 11) Fertile Women who are unable to practice contraception 12) History of seizure or administration of any antiepileptic drugs 13) Contraindication for taking fosphenytoin sodium hydrate 14) Serious allergy to any possible residues in the test product (e.g. any biomaterials used in manufacturing process, gentamicin sulfate, ferucarbotran) or any agents used for the administration of the test product or any inspections during the trial 15) Contraindication for MRI (e.g. a pacemaker, metallic artificial heart valves, an implantable cardioverter defibrillator) 16)Subjects who participate in other clinical trial within 90 days before enrollment. 17) Subjects who are improper on the basis of the judgement by primary investigator or other investigators. Second screening 1-6) The same criteria at first screening 7) Subjects who are improper on the basis of the judgement by primary investigator or other investigators
Target sample size	6

Research contact person
Name of lead principal investigator	1st name Masahito Middle name Last name Kawabori
Organization	Hokkaido University Hospital
Division name	Department of neurosurgery
Zip code	0808638
Address	Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, Japan060-8638
TEL	011-706-5987
Email	kawabori@med.hokudai.ac.jp

Public contact
Name of contact person	1st name Arisa Middle name Last name Miura
Organization	Hokkaido University Hospital
Division name	Clinical Research and Medical Innovation Center
Zip code	0808638
Address	Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, Japan060-8648
TEL	011-706-7735
Homepage URL
Email	amiura0904@huhp.hokudai.ac.jp

Sponsor
Institute	Hokkaido University Hospital
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
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	Hokkaido University Hospital
Address	Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, Japan060-8638
Tel	011-706-5987
Email	kawabori@med.hokudai.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	2017 Year 02 Month 22 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	7
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	Completed
Date of protocol fixation	2016 Year 12 Month 22 Day
Date of IRB	2017 Year 01 Month 20 Day
Anticipated trial start date	2017 Year 03 Month 01 Day
Last follow-up date	2020 Year 09 Month 01 Day
Date of closure to data entry	2020 Year 09 Month 01 Day
Date trial data considered complete	2020 Year 09 Month 01 Day
Date analysis concluded	2021 Year 03 Month 31 Day

Other
Other related information

Management information
Registered date	2017 Year 02 Month 14 Day
Last modified on	2021 Year 06 Month 15 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029942