Safety and Efficacy Study of Autologous BM-MNC Processed by Two Methods for Treating Patients With Chronic Limb Ischemia
Recruitment status was: Not yet recruiting
|Critical Limb Ischemia Peripheral Arterial Disease Buerger's Disease||Device: ResQ processed bone marrow sample Device: Ficoll conventional cell processing method||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Participant)
Primary Purpose: Treatment
|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|
- Cell treatment-related adverse event [ Time Frame: 2-wk after bone marrow transplantation ]
- Temperature,Pulse,Respiration,Blood Pressure
- Routine analysis of blood and urine,
- Liver function(ALT：alanine aminotransferase,AST：aspartate transferase), Renal function(Blood urea nitrogen,Creatinine;) Function of coagulation(APTT,PT,Fib,TT）
- local inflammatory response
- Cell-treatment related death
- Cell-treatment related unexpected amputation.
- ulcer size [ Time Frame: 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.
- rest pain score. [ Time Frame: 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;
- level-1 point: occasional pain which can be recalled;
- level-2 points: the pain often but can be tolerated, without or with a little analgesics;
- level-3 points: often with need of general analgesics;
- 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 [ Time Frame: 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;
- level-1 point, or : Accasionally cold feeling;
- level-2 points: Often with cold feeling;
- level-3 points: significantly cold feeling. and can be significantly improved when using a local insulation.
- level-4 points: significantly cold feeling，and can not be significantly improved when using a local insulation.
- claudication distance (m) [ Time Frame: 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 [ Time Frame: 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.
- Resting TcPO2 (mmHg) [ Time Frame: 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.
- Collateral vessel score [ Time Frame: 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 [ Time Frame: Post bone marrow transplantation:1, 3, 6, 12 months ]Amputation rate and level is recorded.
- Skin microcirculation measurement [ Time Frame: 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 [ Time Frame: 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.
|Study Start Date:||October 2011|
|Estimated Study Completion Date:||April 2013|
|Estimated Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
Experimental: ResQ process group
Autologous BM-MNC is enriched with ResQ process(an automatic cell separator). Then the cell product is transplanted into the ischemia limbs of a patient.
Device: ResQ processed bone marrow sample
Autologous bone marrow is processed with ResQ at point of care, prior to the transplantation
Active Comparator: Ficoll-based conventional method
A conventional method based on Ficoll cell separation is used to process bone marrow.
Device: Ficoll conventional cell processing method
Comparison of different cell processing methods
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01446055
|Contact: Yongquan Gu, MDfirstname.lastname@example.org|
|Xuan Wu Hospital||Not yet recruiting|
|Beijing, Beijing, China|
|Contact: Yongquan Gu, MD 13910002909 email@example.com|
|Principal Investigator: Yongquan Gu, MD|
|Principal Investigator:||Yong-Quan Gu, Dr.||Xuanwu Hospital, Beijing|