Immunonutrition for Diabetic Foot Ulcers

Diabetes-induced peripheral neuropathy can lead to the development of diabetic foot ulcers (DFUs), which can have a devastating effect on patients' lives and can lead to life threatening infection, amputations, and even death. Conventional treatment of DFUs are time consuming, burdensome, costly, and often do not treat the root cause of the problem. Even with proper care, ulcers can take a significantly longer time to heal in diabetic patients due to the altered physiology which does not allow for the proper nutrients and healing factors to mobilize to the site of injury, leaving these ulcers with a poor chance of healing and at high risk for infection and possible amputation. Supplemental immunonutrition therapy may offer a viable, low cost, rapidly scalable, and widely available approach to enhance the body's ability to heal itself. This prospective, randomized pilot study will evaluate the effect of a 6-week daily oral course of a specific combination of immunonutrients, L-Arginine, Omega-3 fatty acids, and Vitamin C, on wound healing in diabetic patients with chronic lower extremity ulcers compared to traditional standard of care. The deliverables of this clinical project will serve to advance a cost-effective added strategy to address a significant unmet clinical need in treatment for the diabetic patient population. Study outcomes will lay the foundation for a multi-site clinical trial to establish the efficacy and cost-effectiveness of this strategy across the health care system.

Diabetes mellitus is one of the most prevalent chronic diseases in the world and its incidence is expected to increase over the next 20 years. Historically there are three described types of diabetes mellitus: Type 1, Type 2, and Gestational. The etiology of disease may vary between types, and our current understanding notes overlap of these types, yet the resulting pathophysiology is the same: poor peripheral blood flow, decreased cellular response at the injury site, elevated glucose levels, and poor nutrient transport. Despite many of these patients having an elevated Body Mass Index (BMI), they are functionally under or malnourished. In addition, some patients develop progressive neurologic dysfunction, called peripheral neuropathy (PN). A common complication of diabetes induced PN is the development of diabetic foot ulcers (DFUs), which can have a devastating effect on patients' lives and can lead to life threatening infection, amputations, and even death.

Conventional treatment of DFUs includes shoe wear modification, self-monitoring, local wound care, brace and shoe offloading, and surgical intervention as well as more sophisticated treatments such as bioengineered cellular technologies and hyperbaric oxygen therapy. These modalities are time consuming, burdensome, costly, and often do not treat the root cause of the problem. Additionally, even with proper care, ulcers can take a significantly longer time to heal in diabetic patients due to the altered physiology which does not allow for the proper nutrients and healing factors to mobilize to the site of injury, leaving these ulcers with a poor chance of healing and at high risk for infection and possible amputation. In contrast to traditional treatment modalities, nutrition therapy has been shown to aide in healing of chronic wounds by providing essential nutrients which were not previously present in necessary amounts in diabetic patients. Nutrition therapy has proven useful in modulating inflammation and the immune response, optimizing glucose control, and attenuating the hypermetabolic response to ulcers, ultimately improving healing and recovery. Thus, supplemental immunonutrition therapy may offer a viable, low cost, rapidly scalable, and widely available approach to enhance the body's ability to heal itself.

This prospective, randomized pilot study will evaluate the effect of a 6-week daily oral course of a specific combination of immunonutrients, L-Arginine, Omega-3 fatty acids, and Vitamin C, on wound healing in diabetic patients with chronic lower extremity ulcers compared to traditional standard of care. Wound characteristics and clinical photographs will be documented throughout the course of the study. Patient-reported pain scores, side effects, and unscheduled visits to emergency departments/urgent care centers will be recorded. Patients randomized to receive immunonutrition supplementation will complete an additional survey detailing their satisfaction with the treatment plan upon completion of their participation in the study. The deliverables of this clinical project will serve to advance a cost-effective added strategy to address a significant unmet clinical need in treatment for the diabetic patient population. Study outcomes will lay the foundation for a multi-site clinical trial to establish the efficacy and cost-effectiveness of this strategy across the health care system.

Eligibility Criteria:
Inclusion Criteria:

* ≥ 18 years of age at the time of informed consent
* Toe blood pressure (TBP) \>40 mmHg
* Hemoglobin A1c \<10% (measured within the previous 6 months)
* Diagnosis of diabetes mellitus
* Presence of at least one new chronic, non-healing (present for ≥4 weeks), lower extremity wound (Werner stage 2-3)
* Documented lipid panel within 3 months of study enrollment
* Documented CMP within 3 months of study enrollment
* Documented ECG within 3 months of study enrollment
* Receiving standard or care defined as sharps debridement, appropriate dressing, and offloading.

Exclusion Criteria:

* Allergy to fish
* Current smoker
* Currently taking any OTC supplements containing Omega-3 fatty acids, L-Arginine, or Vitamin C, or antibiotics
* Presence of at least one of the following diseases or conditions: End stage renal disease as defined by patients who have been diagnosed with Stage 4 kidney disease and are not on hemodialysis or who are on hemodialysis with a GFR consistently \< 15L/min and BUN \> 60, Untreated deep bone infection (osteomyelitis), Currently pregnant or breastfeeding
* Women of child-bearing potential
* Prisoners and other institutionalized individuals
* Any patients who have a legal representative to make medical decisions on their behalf or any individuals who are otherwise deemed as medically incompetent.