NuShield/Affinity for the Treatment of Neuropathic Diabetic Foot Ulcers

Inclusion Criteria:

1. Subject is or greater than 18 years old.
2. Type 1 or Type 2 diabetes.
3. Subject has plantar ulcers of greater than or equal to 4 weeks duration at presentation, unresponsive to standard wound care.
4. Subject's ulcer size >0.5cm2 and < 20cm2 area post-debridement.
5. Subject has well controlled glucose levels, with HbA1c < 10%.
6. Subject has adequate lower extremity perfusion, with Ankle-Brachial Index > 0.8 (note: this is an ABI-equivalent, based on biphasic or triphasic color duplex - PVR or MRA. Diabetics often have peripheral vascular calcification or poorly compressible vessels resulting in abnormally high Ankle-Brachial Indices.) or dorsum transcutaneous oxygen test (TcPO2) > 30 mmHg. Presence of tibial and plantar pulses is preferred.
7. Subject should have no evidence of unresolved gross soft-tissue infection or boney pathology (i.e. osteomyelitis).
8. Subject should have no evidence of underlying co-morbid conditions that would adversely affect wound healing such as: Cancer, Raynaud's syndrome, severe venous insufficiency or uncorrected arterial insufficiency, etc.
9. Subject should not be on medications that compromise healing: cytotoxic chemotherapeutics, etc

Exclusion Criteria:

1. Patients with evidence of skin cancer within or adjacent to the ulcer site.
2. Patients who have signs and symptoms of boney pathology (i.e. osteomyelitis) following debridement.
3. Patients with ulcers on the calcaneus.
4. Patients who have significant arterial disease as determined by ABI, duplex Doppler sonography (PVR) or magnetic resonance angiography (MRA): Ankle-Brachial Index < 0.8 (note: this is an ABI-equivalent, based on biphasic or triphasic color duplex - PVR or MRA. Diabetics often have peripheral vascular calcification or poorly compressible vessels resulting in abnormally high ABIs); dorsum transcutaneous oxygen test (TcPO2) < 30 mmHg; absence of tibial or plantar pulses.

5. Patients who have documented clinically significant medical conditions, which would impair wound healing. This includes:

   • Renal impairment (creatinine >2.5 mg/dL);
   • Hepatic impairment (2XULN);
   • Hematological disorders (abnormities of formed elements);
   • Neurologic disorders resulting in significant impairment of sensory and motor functions as judged by the investigator;
   • Patients with signs and symptoms of cellulitis;
   • Patients with ulcers with sinus tracts associated with an ongoing infection;
   • Patients with active deep vein thrombosis;
   • Patients with uncontrolled diabetes, as demonstrated by increased HbA1C (> 10%);
   • Immunocompromised patients (e.g., lymphoma, AIDS, myelodysplastic disorders)
   • Patients with a history of basal cell carcinomas or actinically induced squamous cell carcinomas which have been effectively treated are not excluded, except if the skin cancer was in the exact location of the target ulcer.
6. Patients with active systemic cancer receiving active cancer therapy

7. Patients who are currently receiving, or have received within 1 week prior to study entry:

   • Adriamycin (doxorubicin), bleomycin, serolimus (Rapamune, rapamycin) and anti-TNFα cytotoxic/immunosuppressive agents;
   • Radiation therapy at the ulcer site;
   • Topical growth factors at the target site (i.e., Regranex®).
8. Patients enrolled in wound or drug investigational agent study for any disease within the past 4 weeks.
9. Patients previously treated with amniotic membrane, PRP/PRFM, stem cell therapy, Apligraf, OrCel, Dermagraft, Graft Jacket, Oasis, stem cell therapy or any other advanced therapy at the target site for 1 month prior to enrollment.
10. Pregnant or breast-feeding.
11. Patients, who in the opinion of the investigator, for any reason other than those listed above, will not be able to complete the study per protocol.