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

• Sponsor: Western University of Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT03174366
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arm: 1
• Actual Duration (Months): 21.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Charcot Joint of Foot	Drug: Denosumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Investigating the Use of Prolia (Denosumab) in the Treatment of Acute Charcot Neuroarthropathy
• Actual Study Start Date: May 16, 2017
• Actual Primary Completion Date: Jun 18, 2018
• Actual Study Completion Date: Mar 6, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [1 year]

   Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Secondary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years and Older
• Sexes Eligible for Study: Male
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Western University of Health Sciences	Pomona	California	United States	91711

Sponsors and Collaborators

• Western University of Health Sciences

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 30, 2019

More Information

Publications

None provided.

• Responsible Party: Western University of Health Sciences
• ClinicalTrials.gov Identifier: NCT03174366
• Other Study ID Numbers: 20159178
• First Posted: Jun 2, 2017
• Last Update Posted: Oct 23, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Arthropathy, Neurogenic; Denosumab

Study Results

Participant Flow

Arm/Group Title	Intervention Group, Receiving Medication
Arm/Group Description	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.
Period Title: Overall Study
STARTED	7
COMPLETED	7
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Intervention Group, Receiving Medication
Arm/Group Description	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.
Overall Participants	7
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 85.7%
>=65 years	1 14.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50 (10.14)
Sex: Female, Male (Count of Participants)
Female	4 57.1%
Male	3 42.9%
Race/Ethnicity, Customized (Count of Participants)
Hispanic	4 57.1%
African-American	1 14.3%
Mixed Hispanic/Native American	1 14.3%
Pacific Islander	1 14.3%
Region of Enrollment (participants) [Number]
United States	7 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention Group, Receiving Medication
Arm/Group Description	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.
Measure Participants	7
Serious adverse event	0 0%
No serious adverse events	7 100%

2. Secondary Outcome

Title	Change in Skin Temperature Difference in Degrees Celsius Between the Affected and Non-affected Limb at 6 Months.
Description	Change in skin temperature difference in degrees Celsius between the affected and non-affected limb at 6 months.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention Group, Receiving Medication
Arm/Group Description	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.
Measure Participants	7
Mean (Standard Deviation) [degrees Celsius]	3.06 (0.78)

Adverse Events

Time Frame	1 year
Arm/Group Title	Intervention Group, Receiving Medication
Arm/Group Description	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.
All Cause Mortality
	Intervention Group, Receiving Medication
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Serious Adverse Events
	Intervention Group, Receiving Medication
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Other (Not Including Serious) Adverse Events
	Intervention Group, Receiving Medication
	Affected / at Risk (%)	# Events
Total	2/7 (28.6%)
Infections and infestations
Cellulitis	1/7 (14.3%)	1
Musculoskeletal and connective tissue disorders
Muscle pain, upper extremity	1/7 (14.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.