Evaluation of Personalized Nutritional Intervention on Wound Healing of Cutaneous Ulcers in Diabetics

Study Overview
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Brief Summary
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The ageing population and the increase in diabetes raise the prevalence of chronic skin ulcers (CCU). In diabetics, precursor cell mobilization decreases. In wounds, the inflammation is prolonged and oxidative stress increases. This is an unfavorable microenvironment for healing. A major risk factor in the development of CCU is nutritional deficiency. Healing needs energy and nutrients for regeneration. In diabetics the malnutrition can be more than 60%. However, although the provision of certain nutrients can improve the healing capacity, it is not a common clinical practice to nutritionally evaluate diabetic with CCU. Exosomes are extracellular vesicles that reflect the physiological state of the cells producing them. Stem cell derivatives exosomes are rich in factors, that can provide a favorable microenvironment for tissue regeneration. The aim of this project is to develop a therapeutic process to accelerate the healing of diabetic CCU, based on the correction of nutritional deficiencies, to improve the regenerative capacity, together with the application of exosomes from mesenchymal stem-cell (MSC) in the wound, creating a microenvironment that favors tissue regeneration. For this, a pilot clinical trial with diabetic patients with CCU is proposed, to evaluate the effect of personalized nutritional supplementation on healing and regenerative capacity.

Official Title
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Evaluation of Personalized Nutritional Intervention Together With the Application of MSC-derived Exosomes on the Regenerative Capacity and Wound Healing of Cutaneous Ulcers in Diabetics

Conditions
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Foot, Diabetic

Intervention / Treatment
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* Dietary Supplement: Personalized Nutritional Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signature of the informed consent Age between 50 and 80 years Diagnosis of Diabetes Mellitus for more than 1 year Documented diagnosis of peripheral artery disease HbA1c < 9% Category 5 in the Rutherford-Becker classification Exclusion Criteria: Poor cognitive function, dementia or psychiatric conditions Osteomyelitis, gangrene, malignancy or immunocompromised disease Thromboangiitis obliterans or Buerger's disease Clinical evidence of invasive infection in the target limb requiring IV antibiotherapy Presence of neuropathic ulcers only Human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) positive.

Ages Eligible for Study
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Minimum Age: 50 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: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nutritional Intervention (NI)<br>In addition to the usual treatment, will receive dietary advice and a nutritional supplement, according to the results of their evaluation in the Endocrinology Service | Dietary Supplement: Personalized Nutritional Intervention<br>* Those with malnutrition criteria will also receive a nutritional supplement (e.g. fortimel cubitan, advanced or extra, Nutricia) or another of similar composition, in case of intolerance to the first option. The aim will be to provide at least 50% of the recommended intakes for the main nutrients related to wound healing.<br>|
| No Intervention: Control (C)<br>Who will continue with their usual treatments in the Diabetic Foot Unit and they will receive dietary advice | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ulcer evaluation | Change from baseline in size ulcer assessed by picture, including ruler to measure their size | Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite measure of markers of nutritional status | Change from baseline in nutritional status assessed from blood samples | Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation | 
| Composite measure of haemogram | Change from baseline in haemogram assessed from blood samples | Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation | 
| Hemoglobin A1c (HbA1c) Test for Diabetes | Change from baseline in HbA1c (%) assessed from blood samples | Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation | 
| Measure of markers of nutritional status, include to thyrotropin | Change from baseline in thyrotropin (mlU/L) assessed from blood samples | Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation | 
| Ultrasensitive C-reactive Protein (CRP) test | Change from baseline in CRP (mg/L) assessed from blood samples | Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation | 
| Quantification of circulating endothelial progenitor cells (EPC) | Change from baseline in total CD34+ or CD133+ cells expressing vascular endothelial growth factor receptor 2 (VEGFR2) analyzed by flow cytometry | Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation | 
| Concentration of stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor A (VEGFA) | Change from baseline in concentration of SDF-1 and VEGFA factors in serum by ELISA | Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dietary Supplementations, Wound Healing, Diabetes Mellitus, Malnutrition