Abstract
This study was designed to assess the antimicrobial effect and tolerability of a single dose of a photo-activated gel containing RLP068 in the treatment for infected foot ulcers in subjects with diabetes. A randomized, double-blind, parallel series, placebo-controlled phase IIa trial was performed with three concentrations of RLP068 (0.10, 0.30, and 0.50 %), measuring total and pathogen microbial load on Day 1 (before and 1 h after topical gel application and photoactivation with 689 nm red light), on Days 3, 8, and 15, as add-on to systemic treatment with amoxicillin and clavulanic acid. Blood samples were also drawn 1, 2, and 48 h after administration for the assessment of systemic drug absorption. The trial was performed on 62 patients aged ≥18 years, with type 1 or type 2 diabetes and infected foot ulcer, with an area of 2–15 cm2 and a maximum diameter ≤4.6 cm. A dose-dependent reduction in total microbial load was observed (−1.92 ± 1.21, −2.94 ± 1.60, and −3.00 ± 1.82 LogCFU/ml for 0.10, 0.30, and 0.50 % RPL068 vs. −1.00 ± 1.02 LogCFU/ml with placebo) immediately after illumination, with a progressive fading of the effect during follow-up. No safety issues emerged from the analysis of adverse events. Systemic absorption of RLP068 was negligible. Photodynamic antimicrobial treatment with RLP068 of infected diabetic foot ulcers is well tolerated and produces a significant reduction in germ load. Further clinical trials are needed to verify the efficacy of this approach as add-on to systemic antibiotic treatment.
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Acknowledgments
The authors would like to thank sites staff involved in the D.A.N.T.E. trial, listed in the Appendix. Moreover, the authors would like to thank Caterina Lamanna for the assistance in the preparation of this manuscript and Ilaria Corti and Laura Checcaglini (employees of L. Molteni & C, Italy) for the D.A.N.T.E. trial management. The study was developed, sponsored, and financially supported by Molteni Therapeutics s.r.l. (Italy). This study had also a support by a grant from Tuscany Region (Italy).
Conflict of interest
Gianfranco Gensini disclosed a financial relationship with the following companies: Burson, GSK, Eli Lilly, Menarini, Siemens, Sigma Tau, JeJ, AstraZeneca, Stroder, and Boheringer Ingelheim. Francesco Dotta disclosed the following: Board membership for Novo Nordisk, Eli Lilly, and Merck Sharp & Dohme; Consultancy for Eli Lilly; and Payment for lectures including service on speakers bureaus for Novo Nordisk. Stefano Genovese disclosed the following: Board membership for Lifescan, Eli Lilly, Abbott, Novo Nordisk, and Janssen Cilag; Consultancy for Takeda and Novartis; and Payment for lectures including service on speakers bureaus for Takeda, Lifescan, and Novartis. Edoardo Mannucci, Matteo Monami, Roberto Anichini, and Fabio Romagnoli: No grant or financial support to declare. Giovanni Navalesi is an employee of L. Molteni & C. (Italy), of that Molteni Therapeutics srl (Italy) is a spin-off. Regarding D.A.N.T.E. study, the Institution of each authors as worked as Principal Investigator or Co-Investigator in D.A.N.T.E. study, received a fee, calculated on the enrolled patient number at own site.
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Communicated by Massimo Federici.
Appendix
Appendix
Study sites
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Coordinating site: Azienda Ospedaliera Universitaria Careggi—Firenze (Italy). Site staff: Stefania Zannoni, Nadia Bartoli, Benedetta Ragghianti, Valentina Vitale.
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Satellite site: Azienda Ospedaliera Universitaria Senese—Siena (Italy).
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Site staff: Cecilia Fondelli, Michela Mancioppi.
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Satellite site: Azienda USL 3—Pistoia (Italy).
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Site staff: Arianna Bernini, Alessandra De Bellis.
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Satellite site: Istituto di Ricovero e Cura a Carattere Scientifico—Istituto Nazionale Riposo e Cura Anziani (INRCA)—Ancona (Italy).
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Site staff: Luigi Lanari, Cristina Gatti.
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Satellite site: Istituto di Ricovero e Cura a Carattere Scientifico Multimedica—Sesto San Giovanni, Milano (Italy).
Site staff: Giacomo Clerici, Maurizio Caminiti, Vincenzo Curci, Antonella Quarantiello, Alessia Scatena, Wanda Vailati, Raffaella Donzelli, Loredana Bucciarelli, Maurizio Rondinelli, Valeria Valdes, Monica Bulgheroni, Daniela Gilardi, Elisabetta Calabretto, Filippo Capone.
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Mannucci, E., Genovese, S., Monami, M. et al. Photodynamic topical antimicrobial therapy for infected foot ulcers in patients with diabetes: a randomized, double-blind, placebo-controlled study—the D.A.N.T.E (Diabetic ulcer Antimicrobial New Topical treatment Evaluation) study. Acta Diabetol 51, 435–440 (2014). https://doi.org/10.1007/s00592-013-0533-3
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DOI: https://doi.org/10.1007/s00592-013-0533-3