Induced Wound Healing by Application of Expanded Bone Marrow Stem Cells in Diabetic Patients With Critical Limb Ischemia

Study Overview
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Brief Summary
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Diabetic foot patients with chronic limb ischemia and without the option for surgical or interventional revascularization were recruited and randomized to the transplant groups or the control group within this clinical trial. These patients are randomized to control or intervention group, whereas the intervention is divided into bone marrow cells administered intramuscular or intraarterial or expanded bone marrow cells administered intramuscular or intraarterial resulting in five distinct groups. To measure the therapeutic effects of the various treatment arms patients were evaluated for (ankle brachial index (ABI), transcutaneous oxygen partial pressure (TcPO2), and reactive hyperemia (Blood Oxygen Level Dependent [BOLD]). Patients also underwent imaging with angiographic methods.

Detailed Description
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Diabetic foot (DF) is a concomitant illness of diabetes mellitus. Diabetes is one of the main causes of non-traumatic amputation worldwide due to severe peripheral arterial occlusive disease with chronic critical limb ischemia being the most abundant problem. Ulceration occurs as failure of oxygenation, nutrient supply and progressive occlusion of larger blood vessels often exacerbates pre-existing microvascular abnormalities. Purified bone marrow mononuclear cells or expanded bone marrow cells enriched in Cluster of Differentiation 90+ (CD90+) mesenchymal stem cells (named tissue repair cells, [TRCs]) are used in the treatment of diabetic ulcers in comparison to bone marrow derived stem cells to induce revascularization of the affected limb and to enhance local perfusion. Cells are administered intramuscular or intraarterial. A control group of patients treated according national guidelines without stem cells serves as comparator. Diabetic foot patients with chronic limb ischemia and without the option for surgical or interventional revascularization were recruited and randomized to the transplant groups or the control group within this clinical trial. To measure the therapeutic effects of the various treatment arms patients were evaluated for (ankle brachial index (ABI), transcutaneous oxygen partial pressure (TcPO2), and reactive hyperemia (Blood Oxygen Level Dependent [BOLD]). Patients also underwent imaging with angiographic methods.

Official Title
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Study on Induced Wound Healing Through Application of Expanded Autologous Bone Marrow Stem Cells in Diabetic Patients With Ischemia-induced Chronic Tissue Ulcers Affecting the Lower Limbs

Conditions
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Diabetic Foot

Intervention / Treatment
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* Biological: tissue repair cells (TRC)
* Biological: bone marrow stem cells (BMC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetes mellitus Type 1 or 2 Peripheral occlusive arterial disease stage III or IV (Fontaine) with chronical ischemia, chronic foot ulcer, degree of severity <5 (Wagner), older than 6 weeks, without acute wound infection Ulcer size 1 - 30cm2, in case of osteomyelitis only one bone should be affected no trend towards healing in the ulcer after one week of standard treatment Angiopathic or angioneuropathic diabetic foot syndrome with no possible option of operative or interventional revascularisation Age 18 - 80 years Declaration of patient consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: control group<br>patients received standard of care wound treatment according guideline of the American Diabetes Association (ADA) | |
| Active Comparator: bone marrow stem cells intraarterial<br>bone marrow stem cells administered intraarterial | Biological: bone marrow stem cells (BMC)<br>* bone marrow stem cells<br>|
| Active Comparator: tissue repair cells intramuscular<br>expanded bone marrow cells enriched in CD90+ mesenchymal stem cells administered intramuscular | Biological: tissue repair cells (TRC)<br>* expanded bone marrow cells enriched in CD90+ mesenchymal stem cells<br>|
| Active Comparator: tissue repair cells intraarterial<br>expanded bone marrow cells enriched in CD90+ mesenchymal stem cells administered intraarterial | Biological: tissue repair cells (TRC)<br>* expanded bone marrow cells enriched in CD90+ mesenchymal stem cells<br>|
| Active Comparator: bone marrow stem cells intramuscular<br>bone marrow stem cells administered intramuscular | Biological: bone marrow stem cells (BMC)<br>* bone marrow stem cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The patient is alive, the patient has not undergone any major amputation, complete primary wound healing has been achieved, no ipsilateral relapse has occurred |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate major amputations Rate of patients with complete ulcer healing Rate of treatment related complications Improvement of ankle brachial index (ABI) Improvement of transcutaneous oxygen partial pressure (TcPO2) Improvement of local perfusion |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peripheral arterial occlusion disease (PAD), diabetic foot, critical limb ischemia (CLI), stem cell therapy