Zoledronic Acid or Methylprednisolone for Active Charcot's Neuroarthropathy of Foot in Patients With Diabetes Mellitus
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|ClinicalTrials.gov Identifier: NCT03289338|
Recruitment Status : Completed
First Posted : September 20, 2017
Last Update Posted : July 16, 2019
Charcot neuropathic osteoarthropathy (CNO) is a progressively destructive process resulting from significant peripheral neuropathy of almost any aetiology. Diabetes mellitus has emerged as the commonest cause of CNO.
The Charcot foot in diabetes poses many clinical challenges in its diagnosis and management. The lacuna primarily lies in delineation of its etio-pathogenesis and consequently in targeted treatment modalities. Although traditional approaches focus on neurotraumatic and neurovascular theories, these fail to explain all the features of CNO, hence, other hypotheses have been put forward.The current belief is that once the disease is triggered in a susceptible individual, it is mediated through a process of uncontrolled inflammation which, in turn, leads to osteolysis, fractures and joint destruction. Of these processes, the involvement of the receptor activator of nuclear factor- кB (RANK) ligand /RANK/osteoprotegerin (OPG) system in the process of acute CNO is particularly appealing and suggests new pharmacological approaches.
Standard modalities of treatment include offloading and casting. Although various trials have analysed the impact of medical agents including bisphosphonates, teriparatide and bone stimulation techniques, the results have been either inconclusive or not translated into clinical practice. Hence, there is no efficacious treatment of active CNO apart from the traditional offloading. In view of recent advances in understanding of the disease process, the target of intervention should, logically, be interruption of the inflammatory cascade and subsequent osteoclast resorption. Zoledronic acid is the most potent bisphosphonate that has been studied in clinical trials to date and has the distinctive profile of strong inhibitory activity on the enzyme farnesyl pyrophosphate synthase, essential for osteoclast function. Methylprednisolone conceivably has a potential benefit by offsetting the RANKL/OPG system involved. There have been conflicting reports with bisphophosphonates in active CNO and Zoledronic acid has been infrequently used despite being the most potent. Glucocorticoids including methylprednisolone have also not been systematically tried in this condition.
We hypothesise that targeting the inflammatory cascade with Methylprednisolone and osteoclast mediated damage by Zoledronic acid will address the basic etiopathogenesis of active CNO and may result in earlier resolution of the disease activity. The above mentioned hypothesis is hence, planned to be tested in a randomised, double-blind, placebo-controlled study.
|Condition or disease||Intervention/treatment||Phase|
|Charcot Arthropathy Diabetes Complications||Drug: Zoledronic Acid Drug: Methylprednisolone Drug: Placebos||Phase 2 Phase 3|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Zoledronic Acid or Methylprednisolone in the Management of Active Charcot's Neuroarthropathy of Foot in Patients With Diabetes Mellitus: A Randomized, Double-blind, Placebo Controlled Trial|
|Actual Study Start Date :||June 1, 2016|
|Actual Primary Completion Date :||December 31, 2018|
|Actual Study Completion Date :||December 31, 2018|
Experimental: Zoledronic acid
Bisphosphonate Zoledronic acid
Drug: Zoledronic Acid
Zoledronic acid 5mg intravenous once a month for 3 months
Other Name: Zoledronate
Active Comparator: Methylprednisolone
Methylprednisolone 1gm intravenous once a month for 3 months
Other Name: MPS
Placebo Comparator: Placebos
Placebo normal saline
Normal saline intravenous once a month for 3 months
Other Name: NS
- Time for resolution of active Charcot foot [ Time Frame: 6 months ]
- Time for reduction in levels of inflammatory cytokines (>= 50%) [ Time Frame: 6 months ]
- Time for radiologic resolution/reduction on MRI [ Time Frame: 6 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03289338
|Department of Endocrinology, PGIMER|
|Chandigarh, India, 160012|
|Study Director:||Anil Bhansali, DM||Postgraduate Institute of Medical Education and Research|