Buerger's Disease, Critical Limb Ischemia, Peripheral Arterial Disease
Conditions
Keywords
Peripheral arterial disease, Buerger's disease, atherosclerotic arterial occlusion, bone marrow mononuclear cell, chronic limb ischemia
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.
Interventions
DEVICEResQ processed bone marrow sample
Autologous bone marrow is processed with ResQ at point of care, prior to the transplantation
DEVICEFicoll conventional cell processing method
Comparison of different cell processing methods
Sponsors
Thermogenesis Corp.
Hebei Medical University
Xuanwu Hospital, Beijing
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cell treatment-related adverse event | 2-wk after bone marrow transplantation | 1. Temperature,Pulse,Respiration,Blood Pressure 2. Routine analysis of blood and urine, 3. Liver function(ALT：alanine aminotransferase,AST：aspartate transferase), Renal function(Blood urea nitrogen,Creatinine;) Function of coagulation(APTT,PT,Fib,TT） 4. ECG（Electrocardiography） 5. local inflammatory response 6. Cell-treatment related death 7. Cell-treatment related unexpected amputation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| rest pain score. | Post bone marrow transplantation: 1，3, 6, 12 months | Scoring the rest pain based on the degree of pain as following five scales): 0 level-0 point: no pain; 1. level-1 point: occasional pain which can be recalled; 2. level-2 points: the pain often but can be tolerated, without or with a little analgesics; 3. level-3 points: often with need of general analgesics; 4. level -4 points: affect sleeping due to the pain, general pain medication being difficult to alleviate. Before transplantation: points; after transplantation: points. |
| cold sensation score | Post bone marrow transplantation:,1，3, 6, 12 months | based on a sense of cold as following five scales: 0 level-0 point: no cold sensation; 1. level-1 point, or : Accasionally cold feeling; 2. level-2 points: Often with cold feeling; 3. level-3 points: significantly cold feeling. and can be significantly improved when using a local insulation. 4. level-4 points: significantly cold feeling，and can not be significantly improved when using a local insulation. |
| claudication distance (m) | Post bone marrow transplantation:1, 3, 6, 12 months | Measurement of claudication distance (m)： For patients with intermittent claudication, treadmill exercise test (no tilt, speed 3km/hr) is employed to measure claudication distance. |
| Resting ABI | Post bone marrow transplantation: 1,3, 6, 12 months | Measurement of ABI(ankle brachial index, ABI): Measure arterial pressure with a laser Doppler, and then calculate the ankle-brachial index, that is a ratio of ankle arterial blood pressure to brachial arterial blood pressure at rest. |
| ulcer size | Post bone marrow transplantation: 1, 3, 6, 12 months | Measuring ulcer area (cm2) and depth (mm)of limb : For each ulcer , photographically record the area and depth with a ruler in order to calculate the ulcer area in square millimeters. |
| Collateral vessel score | Post bone marrow transplantation: 1,3, 6, 12 months | Collateral vessel score: Using DSA(Digital subtraction angiography)or CTA(computed tomographic angiography) to score the collateral vessel formation. A mean score is obtained for each ischemic limb by 3 independent interventionists based on the following 4 level score: 0 (no new collateral vessels) * 1 (A little new collateral vessels) * 2 (moderate new collateral blood vessels) * 3 (Rich new collateral vessels) |
| Amputation rate | Post bone marrow transplantation:1, 3, 6, 12 months | Amputation rate and level is recorded. |
| Skin microcirculation measurement | 1,3,6,12 months post transplantation | using PeriMed laser-Doppler flowmetry measure the skin microcirculation on the same site in the ischemic limb at rest. |
| Resting TBI | Post bone marrow transplantation: 1,3, 6, 12 months | Measurement of TBI（Toe Brachial Index): Measure arterial pressure with a laser Doppler, and then calculate Toe Brachial Index, that is a ratio of toe arterial blood pressure to brachial arterial blood pressure. |
| Resting TcPO2 (mmHg) | Post bone marrow transplantation:1, 3, 6, 12 months | Transcutaneous oxygen pressure(TcPO2) should be measured at the same site in the ischemic limb at rest. |
Countries
China
Contacts
Primary ContactYongquan Gu, MD
Outcome results
None listed