Clinical trial NCT02789033: Efficacy of the Combination of Isosorbide Dinitrate Spray and Chitosan in Diabetic Foot Ulcers
Official title: Efficacy of the Combination of Isosorbide Dinitrate Spray and Chitosan in Diabetic Foot Ulcers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetic Foot Ulcers
Keywords: diabetic foot ulcers
chitosan
isosorbide dinitrate spray
Lead sponsor: University of Guadalajara
Sponsor class: OTHER
First posted: 2016-06-02
Enrollment: 68
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The prevalence of diabetic foot ulceration in the diabetic population is 4-10%; the condition is more frequent in elder patients. It is estimated that about 5% of all patients with diabetes present a history of foot ulceration, while the lifetime risk of diabetic patients developing this complication is 15%. The majority (60-80%) of foot ulcers will heal, while 10-15% of them will remain active, and 5-24% of them will finally lead to limb amputation within a period of 6-18 months after the first evaluation , 2 out of 3 patients with a limb amputation could also be involved in a new amputation in the next year; higher or in the other leg , Eighty-five percent of lower-limb amputations in patients with diabetes are preceded by foot ulceration. The management of chronic diabetic foot ulcers (DFU) suggests multi-disciplinary approaches including control of diabetes, orthotic shoe wear, off-loading device, wound care and surgery in selected cases. However, treatment of DFU remains challenging because of unsatisfactory results from surgical and non-surgical treatments. Many adjunctive therapies are designed to improve the care of DFU including negative pressure wound therapy , ultrasound, recombinant human platelet-derived growth factor-BB (rPDGF-BB) Hyperbaric oxygen and acellular matrix product among others.

Detailed description: A randomized, placebo controlled, double-blind Clinical trial was designed. 60 Patients with diabetic foot ulcers in grade I and II of the classification of Wagner, with leg arm index\> 0.8 and without specific treatment for foot ulcers referred to the experimental and clinical Therapeutic Institute will be included. All patients give written informed consent; previously the protocol was approved for the bioethics committee of the CUCS, of the Guadalajara University, registration number 030-2010. Patients with another type of topical medication will be excluded. Isosorbide dinitrate spray (2.5 mg).

Preparation of chitosan Hydrogels: The composition of gel formulation will be given prior training. ISDN and chitosan gel will be applied handled under aseptic conditions to the wound, and covered with sterile bandages. The patients will be evaluated every 2 weeks (macroscopic study and measurement of the ulcerated area) until 6 views. A second biopsy will be done one week before the finalization of the treatment of 15 weeks. The biopsies will be embedded on paraformaldehyde (4%) and paraffin. Sections of 5 µm were analyzed by a pathologist to determine hypertrophic and hyperplasic capillaries, inflammation and cellular matrix using Hematoxylin \& eosin and Masson's trichrome stains. An immunohistochemical stain was also realized to evaluate several molecular markers such as α-SMA (abcam, Cambridge, MA), Desmin (abcam, Cambridge, MA), VEGF (abcam, Cambridge, MA) and Von Willebrand Factor (Chemicon, CA). (figure 1) Statistical analysis: It will be done using SPSS program for Windows Version 10.0, the results of quantitative variables were expressed in average and standard deviation. The differences between baseline and subsequent pharmacologic intervention measurements will be investigated with the Wilcoxon test. The Mann Whitney U test will be used to compare groups. Frequencies by categories as well as percentages will be quantified for qualitative variables. Comparisons between groups were performed with Chi2. For all comparisons p \< 0.05 will be considered as significant.

Eligibility criteria: Inclusion Criteria:

* Patients with diabetic foot ulcers in grade I and II of the classification of Wagner
* with leg arm index\> 0.8 and
* without specific treatment for foot ulcers referred to the experimental and clinical

Exclusion Criteria:

* Patients with another type of topical medication
* patients with diabetic foot ulcers in grade III and
* with leg arm index \<0.8

Primary outcomes:
measure: Biopsies
timeFrame: 75 days
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Guadalajara
name: Leonel Garcia, PhD
role: PRINCIPAL_INVESTIGATOR
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