Randomized controlled trial of G-CSF-mobilized peripheral blood mononuclear cells transplantation for the treatment of patients with Peripheral Arterial Disease

Phase 3

• Conditions: s disease); Peripheral Arterial Disease (arteriosclerosis obliterans, buerger&#39

• Registration Number: JPRN-UMIN000002280
• Lead Sponsor: Japan Study group of peripheral vascular regeneration cell therapy

Brief Summary

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. MethodsandResults: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.

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-08-01
• Study Completion: 2015-01-01
• Last Update Posted: 20 November 2023

Recruitment & Eligibility

• Status: Complete: follow-up complete
• Sex: All
• Target Recruitment: 144

Inclusion Criteria

Not provided

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/µL or exceeding 10,000/µL., platelets less than 50,000/µL, 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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Progression-free survival

Secondary Outcome Measures

Name	Time	Method
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