UMIN-CTR Clinical Trial

Basic information
Public title	A multi-center clinical trial of tolerance induction using autologous regulatory T cells in liver transplantation
Acronym	Treg multicenter clinical trial
Scientific Title	A multi-center clinical trial of tolerance induction using autologous regulatory T cells in liver transplantation
Scientific Title:Acronym	Treg multicenter clinical trial
Region	Japan

Condition
Condition	End-stage liver failure patients eligible for liver transplantation
Classification by specialty	Hepato-biliary-pancreatic surgery
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To induce tolerance by infusing autologous donor antigen-specific regulatory T cells, generated ex-vivo from peripheral blood mononuclear cells, in living donor liver transplantation.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	Immunosuppressive drug free rate at 30-month after liver transplantation
Key secondary outcomes	1.Amount of immunosuppressive drugs at 1, 2, 3, 4 and 5 years after liver transplantation 2.Drug free interval time after complete cessation of immunosuppressive drugs 3.Successful rate of immunosuppressive drug withdrawal at 30-month after liver transplantation by age 4.Safety of autologous regulatory T cell infusion 5.Safety of leukopheresis

Base
Study type	Interventional

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

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Other
Interventions/Control_1	The liver transplant recipient is given cyclophosphamide (40 mg/kg, iv) on postoperative days (POD) 5, and ex-vivo generated regulatory T cells on POD 13. Postoperative immunosuppression is with conventioal method. The immunosuppressant is reduced to 3/4 daily dose of the twice daily dose at 6 months, which is reduced to 3 times/week, 2 times/ week and 1 time/week every 3 months after confirming normal graft function and liver biopsy. The immunosuppressant is completely discontinued by 18 months after transplantation.
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	Not applicable
Gender	Male and Female
Key inclusion criteria	Recipient 1. A case considered to have eligibility for liver transplantation by the specialists (liver transplant surgeons, physicians, anesthesiologists, radiologists, psychiatrists and pathologists) at the associated institutions 2. A case who is approved for liver transplantation by the medical IRB at the associated institutions 3. A patient over 20 years old. Each institute determine the upper limit of age. 4. A patient who receives informed consent and is well-understood for this protocol and given a consent in writing voluntarily Donor 1. A case considered to have eligibility for liver transplantation donor by the specialists (liver transplant surgeons, physicians, anesthesiologists, radiologists, psychiatrists and pathologists) at the associated institutions 2. A case who is approved for liver transplantation donor by the medical IRB at the associated institutions 3. Platelet >= 100x103/micro L and Hb >= 12.0 g/dL 4. A donor who receives informed consent and is well-understood for this protocol and given a consent in writing voluntarily
Key exclusion criteria	Recipient 1. A person who has no recognition capacity 2. A person who is judged inadequate for the protocol due to the following past history or ongoing infections 1) Bacterial infection such as Treponema pallidum, Neisseria gonorrhea or Mycobacterium tuberculosis 2) Sepsis 3) Malignant diseases (except for hepatocellular carcinoma) 4) Severe metabolic diseases 5) Collagen disease or hematological disorders 6) Transmissible spongiform encephalopathy or dementia 7) A specific hereditary disease or associated familial history 8) Human immunodeficiency virus infection 9) Human T-cell leukemia virus type 1 infection 10) Human parvovirus B19 infection 11) Active infection such as Cytomegalovirus, Epstein-Barr virus or West Nile virus 3. A person 1) with systolic blood pressure under 90 mmHg or over 180 mmHg, 2) with diastolic blood pressure under 50 mmHg or over 100 mmHg 4. A person considered ineligible due to some medical reasons by principal investigator or co-researchers Donor 1. A donor who has no recognition capacity 2. A donor who is judged inadequate for the protocol due to the following past history or ongoing infections 1) Bacterial infection such as Treponema pallidum, Neisseria gonorrhea or Mycobacterium tuberculosis 2) Sepsis 3) Malignant diseases 4) Severe metabolic diseases 5) Collagen disease or hematological disorders 6) Liver diseases 7) Transmissible spongiform encephalopathy or dementia 8) A specific hereditary disease or associated familial history 9) HBV infection 10) HCV infection 11) Human immunodeficiency virus infection 9) Human T-cell leukemia virus type 1 infection 10) Human parvovirus B19 infection 11) Active infection such as Cytomegalovirus, Epstein-Barr virus or West Nile virus 3. A donor 1) with systolic blood pressure under 90 mmHg or over 180 mmHg, 2) with diastolic blood pressure under 50 mmHg or over 100 mmHg 4. A person considered ineligible due to some medical reasons by principal investigator or co-researchers
Target sample size	40

Research contact person
Name of lead principal investigator	1st name Akinobu Middle name Last name Taketomi
Organization	Hokkaido University Graduate School of Medicine
Division name	Department of Gastroenterological Surgery I
Zip code	060-8648
Address	N-14, W-5, Kita-ku, Sapporo 060-8648, Japan
TEL	011-706-5927
Email	taketomi@med.hokudai.ac.jp

Public contact
Name of contact person	1st name Akinobu Middle name Last name Taketomi
Organization	Hokkaido University Graduate School of Medicine
Division name	Department of Gastroenterological Surgery I
Zip code	060-8648
Address	N-14, W-5, Kita-ku, Sapporo 060-8648, Japan
TEL	011-706-5927
Homepage URL
Email	taketomi@med.hokudai.ac.jp

Sponsor
Institute	Hokkaido University Hospital
Institute
Department

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

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

IRB Contact (For public release)
Organization	Hokkaido University Hospital
Address	Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido
Tel	011-706-7061
Email	https://crmic.huhp.hokudai.ac.jp/page/?content=201

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	2018 Year 01 Month 01 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	1
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	2018 Year 01 Month 01 Day
Date of IRB	2018 Year 01 Month 18 Day
Anticipated trial start date	2018 Year 01 Month 01 Day
Last follow-up date	2019 Year 08 Month 28 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 12 Month 28 Day
Last modified on	2020 Year 01 Month 15 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034895