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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2011 by Xuanwu Hospital, Beijing.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborators:
Thermogenesis Corp.
Hebei Medical University
Information provided by (Responsible Party):
Yong-Quan Gu, Xuanwu Hospital, Beijing
ClinicalTrials.gov Identifier:
NCT01446055
First received: September 23, 2011
Last updated: October 8, 2011
Last verified: October 2011

September 23, 2011
October 8, 2011
October 2011
April 2012   (final data collection date for primary outcome measure)
Cell treatment-related adverse event [ Time Frame: 2-wk after bone marrow transplantation ] [ Designated as safety issue: Yes ]
  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.
Cell treatment-related adverse event [ Time Frame: 2-wk after bone marrow transplantation ] [ Designated as safety issue: Yes ]
  1. T,P,R,BP
  2. routine analysis of blood and urine,
  3. liver function(ALT,AST),Renal function(BuN,Cr;)function of coagulation(APTT,PT,Fib,TT)
  4. ECG
  5. local inflammatory response
  6. Cell-treatment related death and unexpected amputation.
Complete list of historical versions of study NCT01446055 on ClinicalTrials.gov Archive Site
  • ulcer size [ Time Frame: Post bone marrow transplantation: 1, 3, 6, 12 months ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    Amputation rate and level is recorded.
  • Skin microcirculation measurement [ Time Frame: 1,3,6,12 months post transplantation ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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.

  • Area size and depth of ulcer and Area size of gangrene in limb: [ Time Frame: Post bone marrow transplantation: 1, 3, 6, 12 months ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    Scoring the resting pain based on the degree of pain as following five scales):

    0 level-0 point: no pain;

    1. level-1 points: 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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    Amputation rate and area will also be measured in the study.
  • laser-Doppler flowmetry [ Time Frame: 1,3,6,12 months post transplantation ] [ Designated as safety issue: No ]
    using PeriMed "laser-Doppler flowmetry" measure the skin microcirculation.
Not Provided
Not Provided
 
Safety and Efficacy Study of Autologous BM-MNC Processed by Two Methods for Treating Patients With Chronic Limb Ischemia
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

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
  • Critical Limb Ischemia
  • Peripheral Arterial Disease
  • Buerger's Disease
  • Device: ResQ processed bone marrow sample
    Autologous bone marrow is processed with ResQ at point of care, prior to the transplantation
  • Device: Ficoll conventional cell processing method
    Comparison of different cell processing methods
  • 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.
    Intervention: Device: ResQ processed bone marrow sample
  • Active Comparator: Ficoll-based conventional method
    A conventional method based on Ficoll cell separation is used to process bone marrow.
    Intervention: Device: Ficoll conventional cell processing method
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
50
April 2013
April 2012   (final data collection date for primary outcome measure)

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
Both
20 Years to 80 Years
No
Contact: Yongquan Gu, MD 13910002909 gu-yq@263.net
China
 
NCT01446055
TGResQ082011
Yes
Yong-Quan Gu, Xuanwu Hospital, Beijing
Xuanwu Hospital, Beijing
  • Thermogenesis Corp.
  • Hebei Medical University
Principal Investigator: Yong-Quan Gu, Dr. Xuanwu hospital capital medical university
Xuanwu Hospital, Beijing
October 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP