Autologous Bone Marrow Mononuclear Cells Therapy in Diabetic Lower Limb Ischemia

Diabetes Clinical Trial

Official title:

Safety and Efficacy Investigation of Patients With Diabetic Lower Limb Ischemia by Transplantation of Autologous Bone Marrow Mononuclear Cells

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01937416
• Other study ID #: 12276102D
• Status: Recruiting
• Phase: Phase 1
• First received: September 4, 2013
• Last updated: December 3, 2013
• Start date: January 2012
• Est. completion date: December 2014

Study information

• Verified date: December 2013
• Source: Hebei Medical University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics CommitteeUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study is to evaluate the safety and efficacy of autologous bone marrow mononuclear cells transplantation in diabetic patients with lower limb ischemia.

Description:

Diabetic lower limb ischemia as severe complication of diabetes influences the life quality of patients and currently the effective treatment for the disease is lacking. Bone marrow mononuclear cells have been proved to have multiple functions including the differentiation and proliferation. In animal model, bone marrow mononuclear cells could induce angiogenesis and may have therapeutic usage for ischemia disease. The investigators thereby design the study to investigate the possible therapy of diabetic lower limb ischemia with autologous bone marrow mononuclear cells. Patient with diabetic lower limb ischemia was treated with colony stimulating factor for improvement of bone marrow hematopoiesis. Then bone marrow was taken and mononuclear cells were isolated with deleting erythrocyte by density gradient centrifugation. Bone marrow mononuclear cells were transplanted into ischemia regions of lower limb through intramuscular injection. The investigators investigated the safety of the therapy with life signs like temperature, pulse, blood pressure, routine analysis of blood and urine etc. post the transplantation. And the efficacy was evaluated with the measurement of ulcer size, rest pain score, cold sensation score, resting ABI, resting TcPO2, collateral vessel score and skin microcirculation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 2014
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

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 diabetic lower limb ischemia

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 bone marrow mononuclear cells transplantation

4. serious infections (such as cellulitis, osteomyelitis, etc.)

5. pregnant female, or reproductive age female who wants to give birth throughout the course of the study

6. life expectancy less than half a year

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes
• Ischemia
• Lower Limb Ischemia

Intervention

Biological:
• autologous bone marrow mononuclear cells
Bone marrow was taken from patient oneself and mononuclear cells were isolated with deleting erythrocyte by density gradient centrifugation. Bone marrow mononuclear cells were transplanted into ischemia regions of lower limb through intramuscular injection.

Locations

Country	Name	City	State
China	the First Hospital of Hebei Medical University	Shijiazhuang	Hebei

Sponsors (1)

Lead Sponsor	Collaborator
Hebei Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cell transplantation related side effect	Temperature,pulse,respiration,blood pressure,routine analysis of blood and urine, liver function,renal function,function of coagulation, ECG,cell transplantation related death and cell transplantation related unexpected amputation	2 week after cell transplantation	Yes
Secondary	ulcer size	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.	Post cell transplantation: 1, 3, 6 months	No
Secondary	rest pain score	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.	Post cell transplantation: 1,3, 6 months	No
Secondary	cold sensation score	based on a sense of cold as following five scales: 0 level-0 point: no cold sensation; level-1 point, or : Occasionally 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.	Post cell transplantation: 1,3, 6 months	No
Secondary	Resting ABI	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.	Post cell transplantation: 1,3, 6 months	No
Secondary	Resting TcPO2 (mmHg)	Transcutaneous oxygen pressure(TcPO2) should be measured at the same site in the ischemic limb at rest.	Post cell transplantation:1, 3, 6 months	No
Secondary	Collateral vessel score	Collateral vessel score: Using 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); (A little new collateral vessels); (moderate new collateral blood vessels); (Rich new collateral vessels)	Post cell transplantation: 1,3, 6 months	No
Secondary	Skin microcirculation measurement	using PeriMed "laser-Doppler flowmetry" measure the skin microcirculation on the same site in the ischemic limb at rest.	1,3,6 months post cell transplantation	No