UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A phase I clinical trial evaluating the safety of allogeneic Adipose Tissue-derived multilineage progenitor cells-transplantation therapy in severe familial hypercholesterolemia patients
Title of the study (Brief title)	A phase I clinical trial evaluating the safety of allogeneic Adipose Tissue-derived multilineage progenitor cells-transplantation therapy in severe familial hypercholesterolemia patients
Region	Japan

Condition
Condition	Severe familial hypercholesterolemia (mainly homozygotes) undergoing LDL-apheresis
Classification by specialty	Cardiology Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	The aim of this study is to evaluate the safety of allogeneic Adipose tissue-derived multilineage progenitor cells-transplantation therapy in severe familial hypercholesterolemia patients undergoing LDL-apheresis.
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase I

Assessment
Primary outcomes	Safety evaluation 1) Systemic adverse events (1) Allergic reaction, rejection reaction and thrombosis by cell-transplantation Fever, eosinophilia, and abnormality of PT-INR, D-Dimer, AST, ALT (2) Complications in the blood vessel by cell-transplantation Bleeding, presence and severity of embolism 2) Adverse events of the puncture site Hematoma, presence and disease severity of the infectious disease 3) Other adverse events Presence, name, type, disease severity, frequency and period of adverse events are evaluated. 4) Other safety evaluations Vital signs (blood pressure, heart rate, body temperature), electrocardiograms, blood test and urinalysis are evaluated.
Key secondary outcomes	Secondary end-point about the safety 1) Safety evaluation about the immunosuppressive drug use Correlation of dose immunosuppressive drug and renal function, blood sugar level, and affection of the infectious disease are evaluated 2) Evaluation of transplanted ADMPC in the systemic circulation The STR-PCR is examined in the systemic circulation before and after transplantation. Secondary end-point about the efficacy 1) Decrease in LDL-C, changes in serum lipid (T-cho, HDL-C, TG, Lp(a)) (1) The rate of change in LDL-C (actual value), LDL-C(Friedewald formula) among 8-11weeks, 13-16 weeks and 17-20 weeks after transplantation (2) The change over time in LDL-C (actual value), LDL-C(Friedewald formula), T-cho, HDL-C, TG and Lp(a) (3) The association with reascension of LDL-C (actual value) and LDL-C (Friedewald formula) after LDL-apheresis and the transplanted cell counts is examined. (4) The association with the change of LDL-C (actual value) and LDL-C (Friedewald formula) in 8-11 weeks, 13-16 weeks and 17-20 weeks and the transplanted cell counts is examined. 2) Secession possibility of LDL-apheresis 3) The association of the background of donor (age, sex and weight) and the quantity of collected adipose tissue is evaluated.

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	Maneuver
Interventions/Control_1	Allogeneic adipose tissue-derived multi-lineage progenitor cells are isolated from donors and cultured. Total 1.6x10^5/kg-1x10^7/kg cells in the heparin-added lactated Ringer aree transplanted into liver via portal vein.
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	The patient who meets the following criteria is enrolled. 1) The patient diagnosed with familial hypercholesterolemia (based on the diagnostic criteria of the Japanese arteriosclerosis society) 2) The patient who undergoes LDL-apheresis 3) The patient who is older than or equal to 20 years old and younger than 80 years when obtained informed consents are obtained 4) The patient who can understand the contents of the study, have the ability for agreement and write a written agreement The patient whose relative (blood relationships in the sixth degree), spouse or relative (by marriage in the third degree) can meet the eligibility criteria of the cell donor and agree to become a cell donor with a written agreement.
Key exclusion criteria	The patients corresponding to any of the following criteria are excluded from the study. 1) The patients who have or are suspected to have a malignant tumor or a precancerous lesion; or have the past history of those within five years 2) The patients who have a coronary disease or cerebrovascular disorder, which require any treatment. 3) The patients who have renal dysfunction, liver dysfunction and blood disorders. 4) The patient who have diabetes mellitus or have more than 6.5% HbA1c. 5) The patient who have an active infectious disease. 6) The patient who have any of infectious disease such as HBV (carrier and the existing infected patient), HCV, HTLV-I (ATLA), HIV, parvoviral B19, Treponema pallidum, gonococcus, tuberculosis, cytomegalovirus, EB virus, one of waist Nile viruses. 7) The patient who requires to have any treatment (surgical care) affecting the liver function test during the study 8) The patient Person with the communicable spongy encephalopathic and doubt and dementia 9) The pregnant patient, the possible pregnant patient or the patient who wishes to have pregnancy during a study 10) The patient who gives breast-feeding 11) The patient who has the past of an alcoholism or the drug dependency within six months before registration 12) The patient who are diagnosed by the doctor operating this study not to be able to recognize the significance of the clinical study from a mental disease. 13) Others, the patient who are diagnosed not to be eligible to be enrolled into this study by the doctor.
Target sample size	4

Research contact person
Name of lead principal investigator	Shizuya Yamashita
Organization	Osaka University Graduate School of Medicine
Division name	Community Medicine
Address	2-2 Yamadaoka, Suita, Osaka, Japan
TEL	06-6879-3633
Email	shizu@cardiology.med.osaka-u.ac.jp

Public contact
Name of contact person	Masahiro Koseki
Organization	Osaka University Graduate School of Medicine
Division name	Cardiology
Address	2-2 Yamadaoka, Suita, Osaka, Japan
TEL	06-6879-3633
Homepage URL
Email	koseki@cardiology.med.osaka-u.ac.jp

Sponsor
Institute	Osaka University Graduate School of Medicine
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	Osaka University Hospital Medical Center for Translational Research
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	YES
Study ID_1	PA8150003
Org. issuing International ID_1	Ministry of Health, Labour, Sports and Welfare
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	大阪大学医学部附属病院（大阪府）

Other administrative information
Date of disclosure of the study information	2016 Year 01 Month 16 Day

Progress
Recruitment status	Terminated
Date of protocol fixation	2015 Year 12 Month 25 Day
Anticipated trial start date	2016 Year 01 Month 15 Day
Last follow-up date	2018 Year 07 Month 26 Day
Date of closure to data entry	2019 Year 06 Month 30 Day
Date trial data considered complete
Date analysis concluded	2019 Year 06 Month 30 Day

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2016 Year 01 Month 16 Day
Last modified on	2019 Year 01 Month 24 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023759