Investigating the Use of Prolia (Denosumab) in the Treatment of Acute Charcot Neuroarthropathy
Condition: Charcot Joint of Foot
MeSH terms: Arthropathy, Neurogenic
Intervention: Denosumab
Intervention description: Subjects will receive medication once following enrollment, and will be monitored for 1 year thereafter.
Intervention MeSH terms: Denosumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: Male
Minimum age: 30 Years
Healthy volunteers: No

Summary:

      Charcot neuroarthropathy (CN) is a debilitating disease primarily affecting poorly controlled
      diabetic patients with peripheral neuropathy. The consequences of CN include ulcerations of
      the foot and ankle, osteomyelitis, and severe musculoskeletal deformity. These consequences
      frequently lead to below-knee amputation of the affected limb.

      Currently treatment options are limited, and no pharmaceutical treatment has been efficacious
      in the medical literature. The purpose of this pilot study is to investigate the potential of
      the medication denosumab for acute stage Charcot neuroarthropathy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men or women > 30 years old

          -  Subject is able and willing to comply with study procedures, and is able to give
             signed and dated consent

          -  Subject meets criteria for diagnosis of Diabetes Mellitus Type 1 or 2, active Charcot
             neuroarthropathy, and peripheral neuropathy

          -  Subjects with serum calcium or albumin-adjusted serum calcium ≥2.0 mmol/L (8.0mg/dL)

        Exclusion Criteria:

          -  Unable to provide signed and dated consent.

          -  Charcot neuroarthropathy of the ipsilateral lower extremity, diagnosed over 1 month
             prior.

          -  Prior foot or ankle surgery of the ipsilateral lower extremity.

          -  Prior amputation at any level of either lower extremity.

          -  Prior foot or ankle fracture of the ipsilateral lower extremity unrelated to the
             current acute CN episode.

          -  Currently has any of the following:

               1. Infection

               2. Foot ulceration

               3. Hypocalcemia

               4. Creatinine clearance less than 30 mL/min or on dialysis

               5. Pre-existing disturbance of mineral metabolism (e.g., hypoparathyroidism unstable
                  on therapy, thyroid or parathyroid surgery, vitamin D deficiency, malabsorption
                  syndromes, excision of small intestine, history of diseases affecting bone
                  metabolism) that has not been effectively corrected or treated.

          -  Have undergone revascularization procedures of the lower extremities.

          -  Female subjects who are pregnant or planning to breastfeed should not participate in
             this study.

          -  Determined to have poor oral hygiene after dental screening or are at increased risk
             for developing osteonecrosis of the jaw.

          -  History of osteonecrosis of the jaw.

          -  History of tooth extraction or other dental surgery within the prior 6 months.

          -  Invasive dental work planned in the next 2 years.

          -  Have a known hypersensitivity to Prolia.

          -  Known use of a bone active medication within the 6 months prior to enrollment.

          -  Liver disease, defined as AST > 2.0x ULN, ALT > 2.0x ULN, TBL > 1.5x ULN.

          -  Malignancy within the last 5 years (except cervical carcinoma in situ or basal cell
             carcinoma)