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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
  Purpose

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.


Condition Intervention Phase
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 Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
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

Resource links provided by NLM:


Further study details as provided by Xuanwu Hospital, Beijing:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.



Estimated Enrollment: 50
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)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01446055

Contacts
Contact: Yongquan Gu, MD 13910002909 gu-yq@263.net

Locations
China, Beijing
Xuan Wu Hospital Not yet recruiting
Beijing, Beijing, China
Contact: Yongquan Gu, MD    13910002909    gu-yq@263.net   
Principal Investigator: Yongquan Gu, MD         
Sponsors and Collaborators
Xuanwu Hospital, Beijing
Thermogenesis Corp.
Hebei Medical University
Investigators
Principal Investigator: Yong-Quan Gu, Dr. Xuanwu hospital capital medical university
  More Information

No publications provided

Responsible Party: Yong-Quan Gu, Director of Vascular Surgery Department, Principal Investigator, Clinical Professor, Xuanwu Hospital, Beijing
ClinicalTrials.gov Identifier: NCT01446055     History of Changes
Other Study ID Numbers: TGResQ082011
Study First Received: September 23, 2011
Last Updated: October 8, 2011
Health Authority: China: Ministry of Health

Keywords provided by Xuanwu Hospital, Beijing:
Peripheral arterial disease
Buerger's disease
atherosclerotic arterial occlusion
bone marrow mononuclear cell
chronic limb ischemia

Additional relevant MeSH terms:
Ischemia
Peripheral Arterial Disease
Peripheral Vascular Diseases
Thromboangiitis Obliterans
Arterial Occlusive Diseases
Arteriosclerosis
Atherosclerosis
Cardiovascular Diseases
Pathologic Processes
Vascular Diseases
Vasculitis

ClinicalTrials.gov processed this record on November 27, 2014