UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Randomized controlled trial of G-CSF-mobilized peripheral blood mononuclear cells transplantation for the treatment of patients with Peripheral Arterial Disease
Title of the study (Brief title)	IMPACT STUDY
Region	Japan

Condition
Condition	Peripheral Arterial Disease (arteriosclerosis obliterans, buerger's disease)
Classification by specialty	Cardiology Nephrology Vascular surgery
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the safety and efficacy of G-CSF-mobilized peripheral blood mononuclear cells transplantation for the patients with PAD(ASO, Buerger's disease), who are unresponsive to standard therapy, we compare the recommended treatment group, the recommended treatment and cells transplantation group, and the cells transplantation group. The recommended therapy is performed based on TASC2 and'Guideline 2 diagnosis and treatment for inferior ASO'edited by Japanese college of angiology.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2
Developmental phase	Phase III

Assessment
Primary outcomes	Progression-free survival
Key secondary outcomes	1) Changes of Fontaine classification or Rutherford classification 2) Overall survival 3) Time-to-amputation 4) Amputation-free survival 5) Ulcer /Gangrene size 6) Severity of ischemic pain in lower limbs 7) ABI (TBI in measurable patients) 8) ICD and ACD

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Cluster
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is not considered as adjustment factor.
Blocking	YES
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Recommended treatment group The recommended therapy is performed based on TASC2 and 'Guideline 2 diagnosis and treatment for inferior ASO' edited by Japanese college of angiology.
Interventions/Control_2	Recommended treatment and Cells transplantation group
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	75 years-old >=
Gender	Male and Female
Key inclusion criteria	1) Patients with ASO or Buerger's disease confirmed obstruction or stenosis by leg angiography 2) Patients whose Fontaine classification is 2-4 and Rutherford classification is 1-5 in either limb. 3) Patients without indication of angioplasty and bypass surgery to arteria poplitea (constricted portion is diffuse or at peripheral micro artery), or uncontrollable the disease by these traditional treatment(No option patients) 4) Nonsmoking for over a month 5) Age is between 20 and 75. Patients who can give informed consent themselves in writing
Key exclusion criteria	1) Patients with severity progression of Fontaine classification or Rutherford classification within 1 month 2) Major amputation of lower limb is planned 3) Patients who performed angioplasty, bypass surgery, other surgical therapy or LDL apheresis within 1 month. 4) Patients who have serious allergic reaction or adverse reaction to G-CSF or apheresis 5) Patients with uncontrolled ischemic heart disease, heart failure or arrhythmia 6) Patients with severe stenotic lesion at major artery in intracranial or extracranial 7) Less than 6 months since last episode of myocardial/brain infarction, brain hemorrhage or TIAs. 8) Dialysis patients of Fontaine4, who have a history of ischemic heart disease, brain infarction or brain hemorrhage. 9) Patients with diabetic proliferating retinopathy (new Fukuda classification BI to BV). 10) Patients with malignant tumor within 3 years 11) Leukocytes less than 4,000/&micro;L or exceeding 10,000/&micro;L., platelets less than 50,000/&micro;L, AST (GOT) exceeding 100 IU/L or ALT (GPT) exceeding 100 IU/L 12) Patients who have coexisting or history of interstitial pneumonia, or take the medicine with possibility of causing interstitial pneumonia 13) Patients who complicated by infection with fever over 38C 14) Patients with splenomegaly 15) Patients with claudication symptom, rest pain, ulcer or gangrene unrelated to primary disease 16) Patients with severe neuropathy in the lower limbs, and be difficult to evaluate in this trial 17) Patients with uncontrollable mental disorders 18) Patients with coexisting or history of hyperfunction of thyroid gland 19) Patient who is within 6 months from the end of other trails 20) The females who are in pregnancy or lactation, may be pregnant, or are planning to become pregnant before the end of trial period. The males who desire pregnancy of partner.
Target sample size	144

Research contact person
Name of lead principal investigator	Takashi Horie
Organization	Sapporo Hokuyu Hospital
Division name	Department of Surgery
Address	6-5-1, Higasisapporo 6-Jo,
TEL	011-865-0111
Email	saiseichiryo@hokuyu_aoth.org

Public contact
Name of contact person	Takashi Horie
Organization	Sapporo Hokuyu Hospital
Division name	Department of Surgery
Address	6-5-1, Higasisapporo 6-Jo,
TEL	011-865-0111
Homepage URL	http://padct.jp/
Email	saiseichiryo@hokuyu-aoth.org

Sponsor
Institute	Japan Study group of peripheral vascular regeneration cell therapy
Institute
Department

Funding Source
Organization	Resarch Foundation for Community Medicine
Organization
Division
Category of Funding Organization	Non profit foundation
Nationality of Funding Organization

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

Secondary IDs
Secondary IDs	YES
Study ID_1	TRIPAD0708
Org. issuing International ID_1	TRI
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2009 Year 08 Month 01 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2009 Year 06 Month 22 Day
Anticipated trial start date	2009 Year 08 Month 01 Day
Last follow-up date	2015 Year 01 Month 01 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Published
URL releasing results	https://www.jstage.jst.go.jp/article/circj/82/8/82_CJ-17-1220/_article
Results	Background:The clinical usefulness of peripheral blood (PB) mononuclear cell (MNC) transplantation in patients with peripheral arterial disease (PAD), especially in those with mild-to-moderate severity, has not been fully clarified. Methods？and？Results:A randomized clinical trial was conducted to evaluate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF)-mobilized PBMNC transplantation in patients with PAD (Fontaine stage 2-3 and Rutherford category 1-5) caused by arteriosclerosis obliterans or Buergers disease. The primary endpoint was progression-free survival (PFS). In total, 107 subjects were enrolled. At baseline, Fontaine stage was 2/3 in 82 patients and 4 in 21, and 54 patients were on hemodialysis. A total of 50 patients had intramuscular transplantation of PBMNC combined with standard of care (SOC) (cell therapy group), and 53 received SOC only (control group). PFS tended to be improved in the cell therapy group than in the control group (P=0.07). PFS in Fontaine stage 2/3 subgroup was significantly better in the cell therapy group than in the control group. Cell therapy-related adverse events were transient and not serious. Conclusions:In this first randomized, large-scale clinical trial of G-CSF-mobilized PBMNC transplantation, the cell therapy was tolerated by a variety of PAD patients. The PBMNC therapy was significantly effective for inhibiting disease progression in mild-to-moderate PAD.
Other related information

Management information
Registered date	2009 Year 08 Month 01 Day
Last modified on	2018 Year 08 Month 08 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002791