Abstract
Introduction
The aim of the study was to investigate the role of the proteolytic fraction from Vasconcellea cundinamarcensis, designated as P1G10, on the healing of chronic foot ulcers in neuropathic patients with diabetes 2.
Methods
Fifty patients were enrolled in a prospective, randomized, double-blind trial, to verify the efficacy and safety of a topical dressing formulated with 0.1% P1G10, intended for wound healing, versus a hydrogel (control) protocol. Upon completion of the intervention, the outcome evaluated the number of patients attaining full epithelization (100%), or at least 80% healing. Statistical analysis compared the data on each group for the significance of the differences.
Results
Collection of data was finished in week 16, and the results were analyzed by intention to treat. The results showed that, in the control group, 5 patients attained 100% ulcer healing, 3 patients ≥ 80% healing and 11 experienced ulcer changes ≤ 80%, and the remainder showed no changes or their wounds became worse. Meanwhile, in the P1G10 group, 11 patients experienced full healing, 4 had healing ≥ 80% and 5 had ulcer changes ≤ lower than 80%, and the remainder showed no changes or their wounds became worse. The healing incidence for the first endpoint (100% healing) showed that the P1G10 group was 2.95-fold more efficacious than the control group (CI 95%) and 2.52-fold (CI, 95%) higher than its control for the second endpoint (80% healing).
Conclusions
These data support the hypothesis that topical application of the proteolytic fraction identified as P1G10 significantly enhances foot ulcer healing compared to hydrogel treatment.
Similar content being viewed by others
References
Global report on diabetes. World Health Organization, Geneva, 2016. 1 Global report on diabetes.
Adeghate J, Nurulain S, Tekes K, Fehér E, Kalász H, Adeghate E. Novel biological therapies for the treatment of diabetic foot ulcers. Expert Opin Biol Ther. 2017;17:979–87.
Pryce TD. A case of perforating ulcers of both feet associated with diabetes and ataxic symptoms. Lancet. 1887;2:11–2.
Abbott CA, Carrington AL, Ashe H, et al. The North-West Diabetes Foot Care Study: incidence of, and risk factors for, new diabetic foot ulceration in a community-based patient cohort. Diabet Med. 2002;19:377–84.
Riaz M, Miyan Z, Zaidi SI, et al. Characteristics and outcomes of subjects with diabetic foot ulceration. Diabet Care. 2012;35:e63.
Moxey PW, Gogalniceanu P, Hinchliffe RJ, et al. Lower extremity amputations—a review of global variability in incidence. Diabet Med. 2011;28:1144–53.
Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009;17:763–71.
Walsh JW, Hoffstad OJ, Sullivan MO, Margolis DJ. Association of diabetic foot ulcer and death in a population-based cohort from the United Kingdom. Diabet Med. 2016;33:1493–8.
Heritier SR, Gebski VJ, Keech AC. Inclusion of patients in clinical trial analysis: the intention-to-treat principle. Med J Aust. 2003;179:438–40.
Prompers L, Huijberts M, Apelqvist J, et al. High prevalence of ischaemia, infection and serious comorbidity in patients with diabetic foot disease in Europe: base-line results from the Eurodiale study. Diabetologia. 2007;50:18–25.
Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012;54:132–73.
Kim YA, Kim ES, Hwang HK, et al. Prevalence and risk factors for the peripheral neuropathy in patients with peripheral arterial occlusive disease. Vasc Special Int. 2014;30:125–32.
Edwards J, Stapley S. Debridement of diabetic foot ulcers. Cochrane Database Syst Rev 2010; 20. https://doi.org/10.1002/14651858.cd003556.pub2 (Art. No.: CD003556.).
Campitiello F, Mancone M, Corte AD, Guerniero R, Canonico S. To evaluate the efficacy of an acellular Flowable matrix in comparison with a wet dressing for the treatment of patients with diabetic foot ulcers: a randomized clinical trial. Updates Surg. 2017;69:523–9.
Cazzell S, Vayser D, Pham H, et al. A randomized clinical trial of a human acellular dermal matrix demonstrated superior healing rates for chronic diabetic foot ulcers over conventional care and an active acellular dermal matrix comparator. Wound Repair Regen. 2017;25:483–97.
Löndahl M, Tarnow L, Karlsmark T, et al. Use of an autologous leucocyte and platelet-rich fibrin patch on hard-to-heal DFUs: a pilot study. J Wound Care. 2015;24:176–8.
Rezvani O, Shabbak E, Aslani A, Bidar R, Jafari M, Safarnezhad S. A randomized, double-blind, placebo-controlled trial to determine the effects of topical insulin on wound healing. Ostomy Wound Manag. 2009;55:22–8.
Tsang MW, Wong WK, Hung CS, et al. Human epidermal growth factor enhances healing of diabetic foot ulcers. Diabet Care. 2003;26:1856–61.
Jimenez JC, Agnew PS, Mayer P et al. Enzymatic debridement of chronic nonischemic diabetic foot ulcers: results of a randomized, controlled trial. Wounds. 2017;29:133–9.
Araújo IC, Defune E, Abbade LP, et al. Fibrin gel versus papain gel in the healing of chronic venous ulcers: a double-blind randomized controlled trial. Phlebology. 2017;32:488–95.
Chandanwale A, Langade S, Sonawane D, Gavai P, et al. A randomized, clinical trial to evaluate efficacy and tolerability of Trypsin:Chymotrypsin as compared to Serratiopeptidase and trypsin: bromelain: rutoside in wound management. Adv Ther. 2017;34:180–98.
HØiby N, Bjarnsholt T, Mose C, et al. ESCMID guideline for the diagnosis and treatment of biofilm infections. Clin Microbiol Infect. 2015;21:S1–25.
Dowd SE, Wolcott RD, Sun Y, McKeehan T, Smith E, Rhoads D. Polymicrobial nature of chronic diabetic foot ulcer biofilm infections determined using bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP). PLoS ONE. 2008;3:e3326.
Otto M. Phenol-soluble modulins. Intern J Med Microbiol. 2014;304:164–9.
Badillo VM. Carica L. vs. Vasconcella St. Hil. (Caricaceae) con la rehabilitación de este último. Ernstia. 2000;10:74–9.
Bravo LM, Hermosilla J, Salas CE. A biochemical comparison between latex from Carica candamarcensis and C. papaya. Braz J Med Biol Res. 1994;27:2831–42.
Gomes FS, de SpÃnola CV, Ribeiro HA, Lopes MT, Cassali CD, Salas CE. Wound-healing activity of a proteolytic fraction from Carica candamarcensis on experimentally induced burn. Burns. 2010;36:277–83.
Lemos FO, Ferreira LA, Cardoso VN, Cassali GD, Salas CE, Lopes MT. Skin-healing activity and toxicological evaluation of a proteinase fraction from Carica candamarcensis. Eur J Dermatol. 2011;21:722–30.
Freitas KM, Barcelos LS, Caliari MV, Salas CE, Lopes MTP. Healing activity of proteolytic fraction (P1G10) from Vasconcellea cundinamarcensis in a cutaneous wound excision model. Biomed Pharmacother. 2017;96:269–78.
Kristman V, Manno M, Côté P. Loss to follow-up in cohort studies: how much is too much? Eur J Epidemiol. 2004;19:751–60.
Acknowledgements
Funding
The funding source for this study was CNPq-Brazil, Grant No 563935/2010/3. The journal´s article-processing charges were paid for by the authors.
Authorship
All named authors meet the International Committee of Medical Journal Editors (ICMJE)Â criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.
Thanks
The authors wish to thank the participants for their involvement in the study. The authors are indebted to Luciana M Siqueira, Abraham Schnaiderman and Prof Elsa Uribe for their technical support during the project.
Disclosures
The named authors Luis AB Tonaco, Flavia L Gomes, Gustavo Velasquez-Melendez, Miriam TP Lopes and Carlos E Salas have nothing to disclose.
Compliance with Ethics Guidelines
The study was approved by the Institutional Research Ethics Committee from Universidade Federal Minas Gerais No 05172412.0.0000.5149 and by Plataforma Brasil with No 179.129 as established in the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Universal Trial number assigned to this study is (UTN)Â U1111-1199-2539. Informed written consent was obtained from all individual participants in the study.
Data Availability
The datasets during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Author information
Authors and Affiliations
Corresponding author
Additional information
Enhanced Content
To view enhanced content for this article go to https://doi.org/10.6084/m9.figshare.5919382.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Tonaco, L.A.B., Gomes, F.L., Velasquez-Melendez, G. et al. The Proteolytic Fraction from Latex of Vasconcellea cundinamarcensis (P1G10) Enhances Wound Healing of Diabetic Foot Ulcers: A Double-Blind Randomized Pilot Study. Adv Ther 35, 494–502 (2018). https://doi.org/10.1007/s12325-018-0684-2
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12325-018-0684-2