Marcos Lopez

A Controlled, Randomized-Blinded Clinical Trial to Assess the Efficacy of a Nitric Oxide Releasing Patch in the Treatment of Cutaneous Leishmaniasis by Leishmania ( V. ) panamensis

A topical nanofiber nitric oxide (NO) releasing patch ( approximately 3.5 mumol NO/cm(2)/day for 20 days, NOP) was compared with intramuscular meglumine antimoniate (Glucantime, 20 mg/kg/day for 20 days) for the treatment of cutaneous leishmaniasis (CL) caused by Leishmania (V.) panamensis in Santander and Tolima, Colombia. A double-blind, randomized, placebo-controlled, clinical trial was conducted to determine whether the NOP is as effective as Glucantime for the treatment of CL. Patients were randomly assigned to Glucantime and placebo patches or NOP and placebo of Glucantime. The cure rates after a 3-month follow-up were 94.8% for the group that received Glucantime compared with 37.1% in the NOP group. Despite the lower efficacy of the NOP versus Glucantime, a significantly lower frequency of non-serious adverse events and a reduced variation in serum markers were observed in patients treated with NOP. Treatment of CL with NOP resulted in a lower effectiveness compared with Glucantime; however, the low frequency of adverse events and the facility of topic administration justify the development of new generations of NOP systems for the treatment of CL.

Double blind, randomized, placebo controlled clinical trial for the treatment of diabetic foot ulcers, using a nitric oxide releasing patch: PATHON

BackgroundDiabetes Mellitus constitutes one of the most important public health problems due to its high prevalence and enormous social and economic consequences. Diabetic foot ulcers are one of the chronic complications of diabetes mellitus and constitute the most important cause of non-traumatic amputation of inferior limbs. It is estimated that 15% of the diabetic population will develop an ulcer sometime in their lives. Although novel therapies have been proposed, there is no effective treatment for this pathology. Naturally produced nitric oxide participates in the wound healing process by stimulating the synthesis of collagen, triggering the release of chemotactic cytokines, increasing blood vessels permeability, promoting angiogenic activity, stimulating the release of epidermical growth factors, and by interfering with the bacterial mitochondrial respiratory chain. Topically administered nitric oxide has demonstrated to be effective and safe for the treatment of chronic ulcers secondary to cutaneous leishmaniasis. However, due to their unstable nitric oxide release, the topical donors needed to be applied frequently, diminishing the adherence to the treatment. This difficulty has led to the development of a multilayer polymeric transdermal patch produced by electrospinning technique that guarantees a constant nitric oxide release. The main objective of this study is to evaluate the effectiveness and safety of this novel nitric oxide releasing wound dressing for the treatment of diabetic foot ulcers.Methods and designA double-blind, placebo-controlled clinical trial, including 100 diabetic patients was designed. At the time of enrollment, a complete medical evaluation and laboratory tests will be performed, and those patients who meet the inclusion criteria randomly assigned to one of two groups. Over the course of 90 days group 1 will receive active patches and group 2 placebo patches. The patients will be seen by the research group at least every two weeks until the healing of the ulcer or the end of the treatment. During each visit the healing process of the ulcer, the patients health status and the presence of adverse events will be assessed. Should the effectiveness of the patches be demonstrated an alternative treatment would then be available to patients.Trial registrationNCT00428727.

Double blind, randomized controlled trial, to evaluate the effectiveness of a controlled nitric oxide releasing patch versus meglumine antimoniate in the treatment of cutaneous leishmaniasis [NCT00317629]

BackgroundCutaneous Leishmaniasis is a worldwide disease, endemic in 88 countries, that has shown an increasing incidence over the last two decades. So far, pentavalent antimony compounds have been considered the treatment of choice, with a percentage of cure of about 85%. However, the high efficacy of these drugs is counteracted by their many disadvantages and adverse events. Previous studies have shown nitric oxide to be a potential alternative treatment when administered topically with no serious adverse events. However, due to the unstable nitric oxide release, the topical donors needed to be applied frequently, making the adherence to the treatment difficult. The electrospinning technique has allowed the production of a multilayer transdermal patch that produces a continuous and stable nitric oxide release. The main objective of this study is to evaluate this novel nitric oxide topical donor for the treatment of cutaneous leishmaniasis.Methods and designA double-blind, randomized, double-masked, placebo-controlled clinical trial, including 620 patients from endemic areas for Leishmaniasis in Colombia was designed to investigate whether this patch is as effective as meglumine antimoniate for the treatment of cutaneous leishmaniasis but with less adverse events. Subjects with ulcers characteristic of cutaneous leishmaniasis will be medically evaluated and laboratory tests and parasitological confirmation performed. After checking the inclusion/exclusion criteria, the patients will be randomly assigned to one of two groups. During 20 days Group 1 will receive simultaneously meglumine antimoniate and placebo of nitric oxide patches while Group 2 will receive placebo of meglumine antimoniate and active nitric oxide patches. During the treatment visits, the medications will be daily administered and the presence of adverse events assessed. During the follow-up, the research group will visit the patients at days 21, 45, 90 and 180. The healing process of the ulcer, the health of the participants, recidivisms and/or reinfection will also be assessed. The evolution of the ulcers will be photographically registered. In case that the effectiveness of the patches is demonstrated, a novel and safe therapeutic alternative for one of the most important public health problems in many countries will be available to patients.