Investigating the Use of Prolia (Denosumab) in the Treatment of Acute Charcot Neuroarthropathy

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.

Study Overview

• Status: Completed
• Conditions: Charcot Joint of Foot
• Intervention / Treatment: Drug: Denosumab

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Pomona, California, United States, 91711
      • Western University of Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group, receiving medication; Subjects in this group will be receiving medication (denosumab)	Drug: Denosumab; Subjects will receive medication once following enrollment, and will be monitored for 1 year thereafter.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 months

Collaborators and Investigators

• Sponsor: Western University of Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2017
• Primary Completion (Actual): June 18, 2018
• Study Completion (Actual): March 6, 2019

Study Registration Dates

• First Submitted: May 11, 2017
• First Submitted That Met QC Criteria: May 30, 2017
• First Posted (Actual): June 2, 2017

Study Record Updates

• Last Update Posted (Actual): October 23, 2019
• Last Update Submitted That Met QC Criteria: October 22, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Arthropathy, Neurogenic; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: 20159178

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes