Mesenchymal Stromal Cell Derivatives in the Treatment of Chronic Diabetic Foot Ulcers Type 1 and 2

Study Overview
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Brief Summary
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The goal of this study is to evaluate the safety and efficacy of using mesenchymal stromal cell derivatives (dac-MSCs) in the treatment of chronic diabetic foot ulcers (type 1 and 2) in adults. A third of the participants will receive dac-MSCs and Triticum vulgare (Fitostimoline) in combination, the other third MSCs and Fitostimoline in combination, and the last third only Fitosimoline. This study will be a randomized, blind, and parallel and controlled-group trial.

Detailed Description
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Conventional treatments such as dry, wet or active dressings are effective only in 50% of patients with diabetic foot ulcer. The remaining 50% of patients have non-responding recoveries that leads to amputation of the compromised limbs. Currently, the administration of mesenchymal stem cells (MSCs) in animal models or in small groups of patients with diabetic foot ulcer has shown to be safe and effective. Particularly, the use of these cells induce regeneration, both in the dermis and the epidermis. Nevertheless, MSC transplantation has some limitations, for instance, time restrictions in the availability of cells due to their isolation and expansion as well as the complex and costly large-scale production. In the same manner, the cryopreservation might cause deleterious effects that affect the biological activity of the cells and a medical professional should conduct the cell administration. In addition, different studies report variability in the results due to the inconsistency in the methods that they used (extraction protocols, cultivation, expansion and administration). The investigators' recent studies in mice with skin lesions, particularly type 1 diabetes, have shown that the presence of the cells is not necessary to promote skin regeneration and the administration of dac-MSCs is sufficient to stimulate would healing.

Official Title
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Mesenchymal Stromal Cell Derivatives: a New Alternative and Potential Product for the Treatment of Diabetic Foot Ulcers 1 and 2

Conditions
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Foot Ulcer, Diabetic

Intervention / Treatment
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* Other: dac-MSCs
* Other: MSCs
* Drug: Fitostimoline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between the ages of 40 and 80 years, inclusive, with Type 1 or 2 diabetes as defined by the American Diabetes Association Stable glycemic control Transcutaneous oxygen measurement > 30 mmHg Ulcer present at least for 1 month Wound size between 0.5 and 5 cm2 Subjects that require endovascular surgical intervention Subjects must have adequate nutrition (albumin level > 2 g/dL and prealbumin level > 15 mg/dL) Exclusion Criteria: Previous or current diagnoses with one of the following: cancer, symptomatic coronary artery disease, brain disease, kidney failure, blood disorders Taking immunosuppressive and cytotoxic drugs Presence of active systemic infection

Ages Eligible for Study
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Minimum Age: 40 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 |
| --- | --- |
| Experimental: dac-MSCs and Fitostimoline<br>Intradermic application of dac-MSCs (1 mL ) in four equidistant points around the ulcer (twice: day 0 and 7) and topical application of fitostimoline every other day | Other: dac-MSCs<br>* Cell-free therapy<br>* Other names: Cell-free therapy;Drug: Fitostimoline<br>* Triticum vulgare<br>* Other names: Triticum vulgare;|
| Active Comparator: MSCs and Fitostimoline<br>Intradermic application of MSCs (500,000 cells/mL) in four equidistant points around the ulcer (once: day 0 ) and topical application of fitostimoline every other day | Other: MSCs<br>* Cell-based therapy<br>* Other names: Cell-based therapy;Drug: Fitostimoline<br>* Triticum vulgare<br>* Other names: Triticum vulgare;|
| Active Comparator: Fitostimoline<br>Topical application of fitostimoline every other day | Drug: Fitostimoline<br>* Triticum vulgare<br>* Other names: Triticum vulgare;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wound size change | Wound size will be assessed using a SilhouetteMobile camera (digital planimetry) | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Granulation tissue percentage | Images will be used to assess the amount of granulation tissue present in the wound | One year | 
| Pigmentation change | Digital images will be used to evaluate color changes in the wound | One year | 
| Presence of Exudate | Visual observation of the wound to determine the presence of exudate | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal stromal cells, Fitostimoline, MSC derivatives, Diabetes