Placental Cells for Diabetic Foot Ulcers

This is a prospective, non-randomized, single institution, Phase 1 safety trial to evaluate the safety of placental stem cells and the rate of diabetic foot ulcer healing in a population of subjects with non-healing diabetic foot ulcers for at least 4 weeks. The trial will also explore the clinical outcomes of placental stem cells treatment on diabetic peripheral neuropathy. Furthermore, the trial will evaluate the effect of the placental stem cells on serum biomarkers associated with diabetic foot ulcers and diabetic peripheral neuropathy (measured pre- and post-treatment) and correlate the biomarker levels with any changes in diabetic foot ulcers and diabetic peripheral neuropathy. Twelve adult subjects with non-healing diabetic foot ulcers for at least four weeks from diagnosis and not more than 12 months with wound sizes ≥ 2 cm2 and ≤ 4 cm2 will be recruited and treated. Subjects will be followed for 12 months after treatment.

• Placenta Stem Cells (Drug): Injection of 30 M placenta stem cells into/around the diabetic foot ulcer and along the anterior and posterior tibial arteries of the index leg.

Primary outcomes

• Number of Injection Sites Bleeding [Month 1]: Number of Injection Sites Bleeding
• Number of Injection Sites Bleeding [Month 3]: Number of Injection Sites Bleeding
• Number of Injection Sites Bleeding [Month 6]: Number of Injection Sites Bleeding
• Number of Injection Sites Bleeding [Month 12]: Number of Injection Sites Bleeding
• Number of Injection Sites infection/inflammation [Month 1]: Number of Injection Sites infection/inflammation
• Number of Injection Sites infection/inflammation [Month 3]: Number of Injection Sites infection/inflammation
• Number of Injection Sites infection/inflammation [Month 6]: Number of Injection Sites infection/inflammation
• Number of Injection Sites infection/inflammation [Month 12]: Number of Injection Sites infection/inflammation
• Number of Injection Sites with damage to surrounding tissue [Month 1]: Number of Injection Sites with damage to surrounding tissue
• Number of Injection Sites with damage to surrounding tissue [Month 3]: Number of Injection Sites with damage to surrounding tissue
• Number of Injection Sites with damage to surrounding tissue [Month 6]: Number of Injection Sites with damage to surrounding tissue
• Number of Injection Sites with damage to surrounding tissue [Month 12]: Number of Injection Sites with damage to surrounding tissue
• Number of Subjects with pain [Month 1]: Number of Subjects with pain
• Number of Subjects with pain [Month 3]: Number of Subjects with pain
• Number of Subjects with pain [Month 6]: Number of Subjects with pain
• Number of Subjects with pain [Month 12]: Number of Subjects with pain
• Number of Subjects with allergic reaction to placental cells [Month 1]: Number of Subjects with allergic reaction to placental cells
• Number of Subjects with allergic reaction to placental cells [Month 3]: Number of Subjects with allergic reaction to placental cells
• Number of Subjects with allergic reaction to placental cells [Month 6]: Number of Subjects with allergic reaction to placental cells
• Number of Subjects with allergic reaction to placental cells [Month 12]: Number of Subjects with allergic reaction to placental cells
• Number of Subjects with worsening of wound [Month 1]: Number of Subjects with worsening of wound
• Number of Subjects with worsening of wound [Month 3]: Number of Subjects with worsening of wound
• Number of Subjects with worsening of wound [Month 6]: Number of Subjects with worsening of wound
• Number of Subjects with worsening of wound [Month 12]: Number of Subjects with worsening of wound

Secondary outcomes

• Diabetic Foot Ulcer (DFU) size [Month 12]: DFU healing in this trial will be assessed by measuring the size of the DFU and plotting open wound size over the 12-month follow-up period.

Other outcomes

• Change in Diabetic Peripheral Neuropathy - Semmes-Weinstein Monofilament and Vibration Test [Months 1, 3, 6 and 12]: The Semmes-Weinstein Monofilament Test is a diagnostic tool used to assess cutaneous touch and pressure sensation. By using calibrated nylon strands that buckle at specific forces, clinicians can evaluate peripheral nerve function and reliably detect the loss of protective sensation, primarily caused by conditions like diabetic neuropathy

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Diagnosed with Type 2 Diabetes mellitus (DM) - for at least 1 year
* Unilateral non-healing Diabetic Foot Ulcer (DFU) > 2 cm2 and ≤ 4 cm2 (length × width) for at least four weeks despite Atrium Health Wake Forest Baptist standard of care treatment (which can include total contact cast, knee high air cast, and/or compression wrap)
* No new diabetes medication for at least 2 weeks pre-treatment
* Subjects must be willing to avoid steroids for the week prior to procedure day

Exclusion Criteria:

* Clinical signs of active infection requiring systemic antibiotic therapy less than 7 days prior to enrollment.
* Radiographic or clinical evidence of active and untreated osteomyelitis at the target ulcer site. Current use of systemic immunosuppressive therapy, including chronic corticosteroids (equivalent to >10 mg/day prednisone for >14 days).
* Hemoglobin (Hgb) A1C >12.0 at screening or time in range for the blood glucose level (TIR) less than 30%. Hb A1c should not be used for patient with hypoalbuminemia or anemia in the past 3 months and for patients with Chronic Kidney disease stage 4. For patients who have Continuous Glucose Monitor (CGM), instead of Hb A1c, TIR (time in range) less than 30 % will be used.
* Patients who are unable / unwilling to tolerate an effective offloading approach. This includes total contact cast, soft felted cast or knee high fracture boot.
* Current alcohol or substance abuse that, in the opinion of the investigators, would interfere with study participation.
* Active malignancy or malignancy related limb amputation.
* Women that are pregnant or planning to become pregnant during the study.
* Patients with albumin levels less than 3.5 or prealbumin levels less than 18.
* Subjects with any conditions that the clinical Investigator believes may jeopardize the safety of the patient to participate in the trial.
* Severe peripheral arterial disease (PAD) (Ankle-Brachial Index (ABI) less than 0.5) or TCOM (Transcutaneous Oximetry Measurement) less than 40 mmHg.
* TWSB > 30 cm2 (total wound surface burden)

• Lucian G. Vlad, MD, Principal investigator, Atrium Health Wake Forest Baptist