Charcot Joint of Foot
Conditions
Brief 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.
Interventions
DRUGDenosumab
Subjects will receive medication once following enrollment, and will be monitored for 1 year thereafter.
Sponsors
Western University of Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
30 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 1 year | Incidence of Treatment-Emergent Adverse Events \[Safety and Tolerability\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Skin Temperature Difference in Degrees Celsius Between the Affected and Non-affected Limb at 6 Months. | 6 months | Change in skin temperature difference in degrees Celsius between the affected and non-affected limb at 6 months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention Group, Receiving Medication Subjects in this group will be receiving medication (denosumab)
Denosumab: Subjects will receive medication once following enrollment, and will be monitored for 1 year thereafter. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Intervention Group, Receiving Medication |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 50 years STANDARD_DEVIATION 10.14 |
| Race/Ethnicity, Customized Race/Ethnicity African-American | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic | 4 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Mixed Hispanic/Native American | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Pacific Islander | 1 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 2 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Incidence of Treatment-Emergent Adverse Events \[Safety and Tolerability\]
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intervention Group, Receiving Medication | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Serious adverse event | 0 Participants |
| Intervention Group, Receiving Medication | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | No serious adverse events | 7 Participants |
Secondary
Change in Skin Temperature Difference in Degrees Celsius Between the Affected and Non-affected Limb at 6 Months.
Change in skin temperature difference in degrees Celsius between the affected and non-affected limb at 6 months.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group, Receiving Medication | Change in Skin Temperature Difference in Degrees Celsius Between the Affected and Non-affected Limb at 6 Months. | 3.06 degrees Celsius | Standard Deviation 0.78 |