Treatment of Chronic Wounds in Diabetic Foot Syndrome With Allogeneic Adipose Derived Mesenchymal Stem Cells

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to investigate efficiency of applying of adipose-derived mesenchymal stem cells (ADSC) in treatment of chronic wounds in diabetic foot syndrome.

Detailed Description
-----------------
The product will contain an active ingredient- human allogeneic adipose-derived mesenchymal stem cells (ADSC) cells suspended in the fibrin solution applied directly onto prepared wound bed, to form thin gel layer on the wound surface.

Official Title
-----------------
Evaluation of the Safety and Efficacy of the Treatment of Chronic Wounds in Diabetic Foot Syndrome With the Use of Allogeneic Stem Cells Isolated From Adipose Tissue

Conditions
-----------------
Diabetic Foot Ulcer

Intervention / Treatment
-----------------
* Biological: Application of allogeneic ADSC stem cells in fibrin gel
* Procedure: Standard care in diabetic foot ulcer


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signing informed consent form. Above the age of 18 Voluntary participation in the research, following the requirements of the protocol and acceptance for procedures related with its implementation Chronic wound in the course of diabetic foot syndrome, with the wound surface between 1 - 25 sq. cm, without evidence of active infection of the wound at the time of qualification to participate in the study Blood level of glycated haemoglobin (HbA1c) <=11% Satisfactory blood supply to the wound verified by the measurement of the oxygen level in the foot tissue (>=30 mmHg), or by the measurement of systolic blood pressure in posterior or anterior tibial artery (>=50 mmHg) of the affected limb. General health condition, which according to the investigator's opinion, allows patient's participation in all study procedures. Exclusion Criteria: Lack of patient's cooperation Wound etiology other than diabetic foot syndrome Clinicaly significant limb ischemia as verified by the measurement of the oxygen level in the foot tissue (<30 mmHg), or by the measurement of systolic blood pressure in posterior or anterior tibial artery (<50 mmHg) Active wound infection, which would require the treatment with antibiotics Known allergy to ingredients of study product (thrombin, penicillin). Active venous thromboembolism Any systemic disease (acute or chronic) in the stage of exacerbation or not stabilized, that in the opinion of the investigator may hinder or make impossible a patient's participation in the study Active cancer during chemotherapy or radiotherapy, or recent cancer, if the remission occured less than 5 years before joining the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allogeneic ADSC cells in fibrin solution<br>Application of allogeneic ADSC stem cells in fibrin gel, to cover wound surface with thin cells layer. Therapy is based on standard procedure of diabetic foot ulcer treatment combined with application of allogeneic ADSC stem cells in fibrin solution onto the wound surface. | Biological: Application of allogeneic ADSC stem cells in fibrin gel<br>* Chronic wounds in diabetic foot ulcer will be covered with ADSC suspended in fibrin gel - single dose will be administered followed by weekly wound control.<br>|
| Active Comparator: Standard care in diabetic foot ulcer with aplication of fibrin gel to cover wound surface.<br>Application of fibrin gel to cover wound surface. | Procedure: Standard care in diabetic foot ulcer<br>* Chronic wounds in diabetic foot ulcer will be covered with fibrin gel followed by weekly wound control.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in wound size | The comparison of the time required for the 50% reduction of initial wound size between patients in both study arms. The wound size changes will be assessed using digital 3D wound imaging medical device with image processing software, according to the following rules: for wounds deeper than 0.5 cm - measurement of wound volume, or for shallow wounds (less than 0.5 cm depth) - measurement of wound surface. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in wound morphology | Clinical assessment of wound morphology (and its changes during the treatment) in each treated patient, as well, as between patients in both study arms, expressed as: the amount (1) and features (2) of wound exudate, the presence of redness (3) and/or edema (4) in the wound surrounding skin, the presence of granular tissue and fibrin (5) or epithelium (6) in the wound bed. The listed parameters will be assessed using simplified questionnaire adopted from Bates-Jensen Wound Assessment Tool (positions 7-13 from B-JWAT). Each of 6 abovementioned features will be assessed semiquantitatively using 1-5 points scale, (with 1 for a best state, and 5 for a worst state). The sum of points allocated to each parameter will be recorded as the wound score and used for further analysis. The healthy skin/healed wound should receive 6 points, whereas active wound, with exudate and inflammation will receive 30 points (the lower = the better / the higher = the worse). | 8 weeks | 
| Changes in pro-angiogenic factors expression | Evaluation of the expression (and its changes during the treatment) of selected pro-angiogenic factors, measured in wound biopsies. The changes will be analyzed for each tested individual separately, and compared between both study arms. | 8 weeks | 
| Changes in wound-associated pain | Evaluation of the wound-associated pain, assessed by the patient using visual analogue scale. The minimum value is 0 and means no pain and the maximum value is 10 and means the worst possible pain. The lower value the better outcome. The changes will be analyzed for each tested individual separately, and compared between both study arms. | 8 weeks | 
| Changes in the quality of life | Evaluation of the patient's quality of life, assessed by the dedicated QoL questionnaire. The QoL questionnaire consists of 10 questions. Each question is scored 1 to 5. The minimum score is 10 and it means the best possible state of health, and the maximum score is 50, which means ,,the worst possible state of health. The changes will be analyzed for each tested individual separately, and compared between both study arms. | 8 weeks | 
| Record of adverse events | Evaluation of the safety of ADSC application, assessed by the occurrence of any adverse events. | 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stromal vascular fraction, adipose-derived mesenchymal stem cells, chronic wounds, diabetes, foot ulcer