UMIN-CTR Clinical Trial

Basic information
Public title	Evaluation of amnion-derived mesenchymal stem cells for treatment-resistant moderate Crohn's disesase
Acronym	Evaluation of amnion-derived mesenchymal stem cells for treatment-resistant moderate Crohn's disesase
Scientific Title	Evaluation of amnion-derived mesenchymal stem cells for treatment-resistant moderate Crohn's disesase
Scientific Title:Acronym	Evaluation of amnion-derived mesenchymal stem cells for treatment-resistant moderate Crohn's disesase
Region	Japan

Condition
Condition	Crohn's disease
Classification by specialty	Medicine in general Gastroenterology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the safety and efficacy of intravenous administration of amnion-derived mesenchymal stem cells on treatment-resistant moderate Crohn's disease
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Adverse events related to acute infusion toxicity
Key secondary outcomes	Adverse events in 52 weeks after first administration of MSCs. Defects of investigational products. CDAI, SESCD and IBDQ 4 weeks after first administration of MSCs and their time-course change up to 52 weeks. Infiltration of macrophages and neutrophils in the inflamed tissue. Serum levels of inflammatory markers (TNF-a, MCP-1, IL-1b, IL-10, MIF).

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	Medicine
Interventions/Control_1	Low dose group: 1,000,000 cells/kg (day 0 and day 7) DIV. High dose group: 4,000,000 cells/kg (day 0 and day 7) DIV. Safety in high dose group will be evaluated after confirmation of safety in 3 cases of low dose group.
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	70 years-old >
Gender	Male and Female
Key inclusion criteria	1. Age 20-69. 2. Diagnosed as definitive Crohn's disease more than 24 weeks before registration. 3. Resistant or not tolerable to at least 2 biological products (Infliximab, Adalimumab, and Ustekinumab). 4. CDAI 200-450 5. Main lesion observed at ileum end or colorectum. 6. Patients who voluntarily signed the Institutional Review Board approved written informed consent.
Key exclusion criteria	(1) Patients with fistula with uncontrollable abscess. (2) Patients with a history of total or subtotal colectomy. (3) Patients with a history of small intestinal resection or short bowel syndrome. (4) Patients with stoma, internal fistula or severe intestinal stricture. (5) Patients who underwent surgery within 4 weeks before informed consent. (6) Patients with a history of cancer in 5 years. (7) Patients who received any medicine or treatment not allowed certain period before registration, and other medicine or treatment for clinical trials, and patients who received any medicine or treatment not allowed to start, stop or change the dose. (8) Patients with uncontorollable systemic disease. (9) Laboratory tests within these ranges 1) Hemoglobin <8.0 g/dL 2) White blood cell count <3,000/microliter 3) Lymphocyte count <500 microliter 4) AST >3x upper limit 5) ALT >3x upper limit 6) Total bilirubin >2.0 mg/dL 7) Serum creatinine >2x upper limit (10) Patients who can not keep SpO2 of >94% (11) Patients positive for HIV-Ab, HTLV-1-Ab, HBs Ag, HCV-Ab. (12) Patients with uncontrollable severe infectious disease. (13) Patients with severe hypersensitivity to bovine-derived constituents, human serum albumin and gentamicin. (14) Patients with cancer, dysplasia or adenomatous polyp which needs to be treated in the colorectum. (15) Patients with a history of hypersensitivity to iodine or iodine-containing contrast agent. (16) Patients who had underwent any other treatment with cell therapy product. (17) Patients with a history of any severe neurological disorder. (18) Patients in pregnancy or breast-feeding, patients who want to be pregnant, patients who can not prevent conception. (19) Patients considered as ineligible to the study.
Target sample size	12

Research contact person
Last name of lead principal investigator	1st name Middle name Last name Shunsuke Ohnishi
Organization	Hokkaido University Hospital
Division name	Department of Gastroenterology and Hepatology
Zip code
Address	N15, W7, Kita-ku, Sapporo, Japan
TEL	011-706-1161
Email	sonishi@pop.med.hokudai.ac.jp

Public contact
1st name of contact person	1st name Middle name Last name Shunsuke Ohnishi
Organization	Hokkaido University Hospital
Division name	Department of Gastroenterology and Hepatology
Zip code
Address	N15, W7, Kita-ku, Sapporo, Japan
TEL	011-706-1161
Homepage URL
Email	sonishi@pop.med.hokudai.ac.jp

Sponsor
Institute	Hokkaido University
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Government offices of other countries
Nationality of Funding Organization	JAPAN

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

IRB Contact (For public release)
Organization
Address
Tel
Email

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	北海道大学病院（北海道）、兵庫医科大学病院（兵庫県）

Other administrative information
Date of disclosure of the study information	2017 Year 11 Month 13 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	2017 Year 09 Month 17 Day
Date of IRB	2017 Year 09 Month 19 Day
Anticipated trial start date	2017 Year 11 Month 01 Day
Last follow-up date	2019 Year 10 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2017 Year 11 Month 06 Day
Last modified on	2019 Year 05 Month 27 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034088