Clinical trial NCT01446055: Safety and Efficacy Study of Autologous BM-MNC Processed by Two Methods for Treating Patients With Chronic Limb Ischemia
Official title: Transplantation of Autologous BM-MNC Processed by ResQ Separator and Conventional Manual Method for Patients With Chronic Limb Ischemia: a Multi-center Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Critical Limb Ischemia
Peripheral Arterial Disease
Buerger's Disease
Keywords: Peripheral arterial disease
Buerger's disease
atherosclerotic arterial occlusion
bone marrow mononuclear cell
chronic limb ischemia
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: Thermogenesis Corp.
name: Hebei Medical University
First posted: 2011-10-04
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Using autologous bone marrow mononuclear cells (BM-MNC) to treat patients with chronic limb ischemia has been proved safe and effective. However, processing bone marrow by Ficoll density gradient centrifugation is not only time consuming but also expensive. Manually processing of bone marrow also results in large variation in therapeutic cell quantity and quality which directly leads deviation of safety and efficacy of the cell therapy. This study is aiming to compare an automated bone marrow processing system with a conventional manual method in term of safety and efficacy.

Detailed description: Using autologous bone marrow mononuclear cells (BM-MNC) to treat patients with chronic limb ischemia has been proved safe and effective. However, processing bone marrow by Ficoll density gradient centrifugation is not only time consuming but also expensive. Manually processing of bone marrow also results in large variation in therapeutic cell quantity and quality which directly lead deviation of safety and efficacy of the cell therapy. This study is aiming to compare an automated bone marrow processing system with a conventional manual method in term of safety and efficacy.

ResQ system developed by Thermogenesis in USA provides an automatic cell processing system for bone marrow. The system takes less than 30 minutes to concentrate the therapeutic mononuclear cells including stem cells in a closed system without adding any additive such as separation reagent (Ficoll). The system also be able to be operated at point of care.

The study is designed to prove no inferior of safety and efficacy of bone marrow cells processed by ResQ to those of cells using conventional manual method. The conventional manual method is involved Ficoll density gradient centrifugation and cell washing stems in an open system. Each of test arms (ResQ vs manual method) consists of 25 patients. The primary outcome is safety which is measured by cell treatment-related adverse events. The secondary endpoints include resting ankle-brachial pressure index (ABI)and toe brachial pressure index (TBI) , transcutaneous oxygen pressure (TcPO2), claudication distance, rest pain scale evaluation, collateral vessel scale, etc.

Eligibility criteria: Inclusion Criteria:

1. fontaine's stage 2-4 or resting ABI \<0.7
2. age between 20 and 80 years old
3. sign informed consent, voluntary subjects
4. diagnosis of lower extremity arterial occlusive disease, or diabetic lower limb ischemia, or Buerger's disease

Exclusion Criteria:

1. poorly controlled diabetes (HBA1c\> 7.0%) and proliferative retinopathy (III-IV stage)
2. malignancy history in the past five years or serum level of tumor markers elevated more than doubled
3. severe heart, liver, kidney, respiratory failure or poor general condition can not tolerate BM-MNC transplantation
4. serious infections (such as cellulitis, osteomyelitis, etc.)or gangrene that a major amputation cannot be avoided
5. aortic or iliac or common femoral artery occlusion
6. pregnant female, or reproductive age female who wants to give birth throughout the course of the study
7. life expectancy less than a year

Primary outcomes:
measure: Cell treatment-related adverse event
timeFrame: 2-wk after bone marrow transplantation
Secondary outcomes:
measure: ulcer size
timeFrame: Post bone marrow transplantation: 1, 3, 6, 12 months
measure: rest pain score.
timeFrame: Post bone marrow transplantation: 1，3, 6, 12 months
measure: cold sensation score
timeFrame: Post bone marrow transplantation:,1，3, 6, 12 months
measure: claudication distance (m)
timeFrame: Post bone marrow transplantation:1, 3, 6, 12 months
measure: Resting ABI
timeFrame: Post bone marrow transplantation: 1,3, 6, 12 months
measure: Resting TcPO2 (mmHg)
timeFrame: Post bone marrow transplantation:1, 3, 6, 12 months
measure: Collateral vessel score
timeFrame: Post bone marrow transplantation: 1,3, 6, 12 months
measure: Amputation rate
timeFrame: Post bone marrow transplantation:1, 3, 6, 12 months
measure: Skin microcirculation measurement
timeFrame: 1,3,6,12 months post transplantation
measure: Resting TBI
timeFrame: Post bone marrow transplantation: 1,3, 6, 12 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuan Wu Hospital
state: Beijing
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Yong-Quan Gu, Dr.
role: PRINCIPAL_INVESTIGATOR
References: