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

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

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

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.

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

Who will continue with their usual treatments in the Diabetic Foot Unit and they will receive dietary advice

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.

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

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)

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

Change from baseline in diagnosis of malnutrition assessed by Global Leadership Initiative on malnutrition (GLIM criteria)

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

Body weight and height will be combined to report body mass index (BMI) in kg/m^2. Change from baseline in BMI

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

waist and hip circumferences (cm) will be combined to report Waist and Hip Ratio (WHR). Change from baseline in WHR

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

Change from baseline in body fat assessed by multifrequency bioimpedaciometry and bioelectrical impedance vector analysis

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

Change from baseline in muscle mass assessed by multifrequency bioimpedaciometry and bioelectrical impedance vector analysis

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

Change from baseline in hydration status assessed by multifrequency bioimpedaciometry and bioelectrical impedance vector analysis

Baseline, 30 days after treatment initiation, 60 days after treatment initiation and 90 days after treatment initiation

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.

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