Clinical Trial: Safety and Efficacy Study of Autologous BM-MNC Processed by Two Methods for Treating Patients With Chronic Limb Ischemia

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

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

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 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 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.

Current Primary Outcome: Cell treatment-related adverse event [ Time Frame: 2-wk after bone marrow transplantation ]

Original Primary Outcome: Cell treatment-related adverse event [ Time Frame: 2-wk after bone marrow transplantation ]

Current Secondary Outcome:

• 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;

  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 [ 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;

  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) [ 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.

Original Secondary Outcome:

• Area size and depth of ulcer and Area size of gangrene in limb: [ Time Frame: Post bone marrow transplantation: 1, 3, 6, 12 months ]

  Measuring ulcer area (cm2) and depth (mm)of limb and Area size of gangrene :

  For each ulcer and gangrene, photographically record the area and depth with a ruler in order to calculate the ulcer area in square millimeters.

• Scoring the resting pain scale. [ Time Frame: Post bone marrow transplantation: 1，3, 6, 12 months ]

  Scoring the resting 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.

• Limbs 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;

  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.
• Intermittent claudication measurement: pain-free walking time (min) or claudication distance (m) [ Time Frame: Post bone marrow transplantation:1, 3, 6, 12 months ]

  Measurement of claudication distance (m) or pain-free walking time (minutes):

  For patients with intermittent claudication, treadmill exercise test (no tilt, speed 3km/hr) is employed for the determination based on the following scale:

  0: walking ≥ 500 m, no pain;

  1. walk 400 ~ 499m, there is pain;
  2. walk 300 ~ 399m, there is pain;
  3. walk 100 ~ 299m, there is pain;
  4. unable to walk with resting pain or walk <100m, with pain
• Determination of resting ABI and TBI; [ Time Frame: Post bone marrow transplantation: 1,3, 6, 12 months ]

  Measurement of ABI(ankle brachial index, ABI)and TBI（Toe Brachial Index）;:

  Measure arterial pressure with a laser Doppler, and then calculate the ankle-brachial index and TBI（Toe Brachial Index）;:

  that is a ratio of ankle or toe arterial blood pressure to brachial arterial blood pressure.

• Measurement of TcPO2 (mmHg) [ Time Frame: Post bone marrow transplantation: 1,3, 6, 12 months ]
  Transcutaneous oxygen pressure(TcPO2) and Regional perfusion index (RPI) is employed. Regional perfusion index (regional perfusion index, RPI) is a ratio of TcOP2 of the affected limb to that of the pectoralis major. Regional perfusion index is able to eliminate the variation caused by the age, cardiac output and arterial oxygen pressure and other factors which have the impact on local tissue oxygen partial pressure, standardizing oxygen partial pressure value. Researchers should performs the measurement at the same preselected position.
• Digital subtraction angiography (DSA) or CTA [ Time Frame: Post bone marrow transplantation:1, 3, 6, 12 months ]

  Digital subtraction angiography (DSA)or CTA:

  can be used to observe in collateral vessel formation and to score, sub-4: 0 (no new collateral vessels),

  • 1 (A little new collateral vessels),
  • 2 (In the amount of new collateral blood vessels)
  • 3 (Rich new collateral vessels).
• Amputation rate and area [ Time Frame: Post bone marrow transplantation:1, 3, 6, 12 months ]
  Amputation rate and area will also be measured in the study.
• laser-Doppler flowme
  
  Information By: Xuanwu Hospital, Beijing
  

  Dates:
  Date Received: September 23, 2011
  Date Started: October 2011
  Date Completion: April 2013
  Last Updated: October 8, 2011
  Last Verified: October 2011