Efficacy of the Combination of Isosorbide Dinitrate Spray and Chitosan in Diabetic Foot Ulcers

Diabetic Foot Ulcers Clinical Trial

Official title:

Efficacy of the Combination of Isosorbide Dinitrate Spray and Chitosan in Diabetic Foot Ulcers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02789033
• Other study ID #: 030-2010
• Status: Completed
• Phase: Phase 3
• Start date: June 2015
• Est. completion date: August 2015

Study information

• Verified date: December 2020
• Source: University of Guadalajara
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Foot
• Diabetic Foot Ulcers
• Foot Ulcer
• Ulcer

Intervention

Drug:
• Chitosan
Chitosan chemically is a high-molecular-weight linear polycationic heteropolysaccharide comprising copolymers of 1,4-linked D-glucosamine and N-acetyl-D-glucosamine
• Isosorbide dinitrate
Isosorbide dinitrate (ISDN), is an organic nitrate, is a vasodilator with effects on both arteries and veins. The chemical name of ISDN is 1,4:3,6-dianhydro-D-glucitol 2,5-dinitrate
• Placebo
placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Guadalajara

References & Publications (11)

Alexiadou K, Doupis J. Management of diabetic foot ulcers. Diabetes Ther. 2012 Nov;3(1):4. doi: 10.1007/s13300-012-0004-9. Epub 2012 Apr 20. — View Citation

Andrews KL, Irvine JC, Tare M, Apostolopoulos J, Favaloro JL, Triggle CR, Kemp-Harper BK. A role for nitroxyl (HNO) as an endothelium-derived relaxing and hyperpolarizing factor in resistance arteries. Br J Pharmacol. 2009 Jun;157(4):540-50. doi: 10.1111/j.1476-5381.2009.00150.x. Epub 2009 Mar 26. — View Citation

Chabbert-Buffet N, LeDevehat C, Khodabandhelou T, Allaire E, Gaitz JP, Tribout L, Abdoucheli-Baudot N, Vayssairat M. Evidence for associated cutaneous microangiopathy in diabetic patients with neuropathic foot ulceration. Diabetes Care. 2003 Mar;26(3):960-1. — View Citation

Girach A, Manner D, Porta M. Diabetic microvascular complications: can patients at risk be identified? A review. Int J Clin Pract. 2006 Nov;60(11):1471-83. Review. — View Citation

Raafat D, von Bargen K, Haas A, Sahl HG. Insights into the mode of action of chitosan as an antibacterial compound. Appl Environ Microbiol. 2008 Jun;74(12):3764-73. doi: 10.1128/AEM.00453-08. Epub 2008 May 2. Erratum in: Appl Environ Microbiol. 2008 Dec;74(23):7455. — View Citation

Reiber GE, Lipsky BA, Gibbons GW. The burden of diabetic foot ulcers. Am J Surg. 1998 Aug;176(2A Suppl):5S-10S. Review. — View Citation

Richards AM, Floyd DC, Terenghi G, McGrouther DA. Cellular changes in denervated tissue during wound healing in a rat model. Br J Dermatol. 1999 Jun;140(6):1093-9. — View Citation

Schäffer MR, Tantry U, Efron PA, Ahrendt GM, Thornton FJ, Barbul A. Diabetes-impaired healing and reduced wound nitric oxide synthesis: a possible pathophysiologic correlation. Surgery. 1997 May;121(5):513-9. — View Citation

Sezer AD, Cevher E, Hatipoglu F, Ogurtan Z, Bas AL, Akbuga J. Preparation of fucoidan-chitosan hydrogel and its application as burn healing accelerator on rabbits. Biol Pharm Bull. 2008 Dec;31(12):2326-33. — View Citation

Tiaka EK, Papanas N, Manolakis AC, Maltezos E. The role of hyperbaric oxygen in the treatment of diabetic foot ulcers. Angiology. 2012 May;63(4):302-14. doi: 10.1177/0003319711416804. Epub 2011 Aug 25. Review. — View Citation

Xie X, McGregor M, Dendukuri N. The clinical effectiveness of negative pressure wound therapy: a systematic review. J Wound Care. 2010 Nov;19(11):490-5. Review. Erratum in: J Wound Care. 2011 Feb;20(2):89. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biopsies	Histological changes in ulcers	75 days

External Links

•   The outcome of management of diabetic foot ulceration (DFU) is poor and insufficient. DFU therapy includes the standard management as debridement of the wound, revascularization procedures,off-loading of the ulcer and antibacterial actions,