Healing of Diabetic Ulcers with Gaseous Nitric Oxide Generated from Room Air Diabetic foot ulcers (DFUs) are a frequent and debilitating complication of diabetes, and affect 1-2.5 million patients in the US. Many DFUs remain unhealed, leading to extensive hospitalizations and the increased risk of infections, amputations, and death. Patients with DFUs that do not respond to the standard of care treatment require advanced therapeutic options that still have significant failures, leading to ove 82,000 diabetic patients per year ultimately needing amputations. The economic impact of chronic DFU's on society is enormous, with the cost of treating both DFUs and amputations exceeding $11 billion in 2001. Clearly, current treatment methods are inadequate, and a more effective, less disruptive therapy is urgently needed. Nitric oxide (NO) is a key signaling molecule that is crucially involved in multiple aspects of normal wound healing. Studies in diabetic patients have demonstrated the importance of endogenous NO in wound healing, and that reduced bioavailability of NO is associated with the impaired healing of chronic DFUs. Levels of wound fluid nitrates, a stable NO metabolite and biomarker, are depressed in DFUs that fail to heal, indicating that low NO bioavailability is associated with non-healing DFUs. NitricGen, Inc. is an early stage company that is researching a novel plasma technology to electronically generate gaseous nitric oxide (eNO) in a well-controlled manner from ambient air. The ultimate goal is to develop a simple, compact device, which patients can use at home, that provides a daily 60-second dose of NO via a hand-held applicator onto the patient's DFU, to increase the incidence of complete wound healing. This Phase I project has two aims. Specific Aim 1: Research, design, build and bench test four stand-alone portable eNO generating devices for use in a pre-clinical laboratory testing. Specific Aim 2: Research wound healing in a diabetic mouse model by comparing results of the eNO treatment to a placebo. If successful, this study would be the first to demonstrate that short-duration, exogenous NO treatment improves wound healing in a diabetic animal model. This Phase I study would provide support for a Phase II prospective, randomized, double-blind, placebo-controlled clinical study in patients with DFUs. NitricGen's founders have more than 60 years' combined experience in the design and approval of nitric oxide delivery systems and have been responsible for developing seven nitric oxide delivery systems for clinical and commercial use. This includes the first FDA-approved system, which defined important FDA performance and safety requirements that all other nitric oxide delivery devices are required to meet.
Public Health Relevance Statement: Public Health Relevance: Diabetic foot ulcers (DFUs) are a common, challenging complication of diabetes that affect 1-2.5 million patients in the US, and often do not heal well-o a t all. Nitric oxide (NO) plays an important role in normal wound healing. NitricGen will design and build stand-alone, portable nitric oxide generating devices and will then test them to find out if brief daily nitric oxide treatments will improve wound healing in diabetic mice.
NIH Spending Category: Diabetes
Project Terms: active method; Affect; Air; Amputation; Animal Model; Biological Availability; Biological Markers; Biopsy; Cessation of life; Chronic; Clinic; Clinical; Clinical Research; Complications of Diabetes Mellitus; Computer software; cost; Depressed mood; design; Devices; diabetic; Diabetic Foot Ulcer; Diabetic mouse; diabetic patient; Diabetic ulcer; Dose; Double-Blind Method; economic impact; Evaluation; experience; Failure (biologic function); FDA approved; Functional disorder; Goals; Government; Hand; Healed; healing; Home environment; Hospitalization; human NOS3 protein; Impaired wound healing; improved; Incidence; Infection; Laboratories; Liquid substance; Measures; meetings; Methods; Modeling; mouse model; Mus; Nitrates; Nitric Oxide; non-diabetic; novel; Patients; Performance; Persons; Phase; phase 1 study; Placebo Control; Placebos; Plasma; Play; pre-clinical; preclinical study; pressure; prospective; public health relevance; Randomized; Rattus; Regimen; Research; Research Design; Risk; Role; Safety; Signaling Molecule; Societies; Staging; standard of care; Streptozocin; success; System; Technology; Testing; Therapeutic; Time; tissue oxygenation; wound; Wound Healing
