Diabetes Complications Clinical Trial
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
Verified date | July 2019 |
Source | Postgraduate Institute of Medical Education and Research |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 36 |
Est. completion date | December 31, 2018 |
Est. primary completion date | December 31, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility |
Inclusion Criteria: Patients with Diabetes mellitus with active Charcot neuroarthropathy of foot as per following criteria: Clinical criteria 1. Warm, swollen and erythematous foot 2. Skin temperature exceeding 2°C at the clinically suspected site of the affected foot compared with a similar site on the contralateral foot (infrared thermometer) Radiologic criteria MRI suggestive of acute CNO- 1. Osteopenia 2. Joint subluxation 3. Normal or low normal marrow signal on T1 MRI 4. Bone marrow edema on T2W MRI 5. Microfractures 6. Cortical disruption 7. Several joints or bones 8. Preserved periarticular subcutaneous fat Exclusion Criteria: 1. Infected foot ulcer 2. Osteoporosis at lumbar spine or hip 3. Gouty arthritis 4. Active peptic ulcer disease 5. Any prior long term steroid intake for asthma, SLE, RA or IBD in the last 3 months 6. eGFR 45 ml/min or less 7. Active dental caries 8. Active upper gastrointestinal disease 9. Uncorrected Vitamin D deficiency 10. Peripheral vascular disease (ABI 0.9 or less) |
Country | Name | City | State |
---|---|---|---|
India | Department of Endocrinology, PGIMER | Chandigarh |
Lead Sponsor | Collaborator |
---|---|
Postgraduate Institute of Medical Education and Research |
India,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Time for resolution of active Charcot foot | 6 months | ||
Secondary | Time for reduction in levels of inflammatory cytokines (>= 50%) | 6 months | ||
Secondary | Time for radiologic resolution/reduction on MRI | 6 months |
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