Clinical Trial: Efficacy of Teriparatide in Diabetic Inactive Charcot Neuroarthropathy of Foot
Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional
Official Title: To Study the Efficacy of Teriparatide in Improving Remodeling of Foot Bones in Chronic Charcot Neuroarthropathy in Patients With Diabetes Mellitus.
Brief Summary:
Diabetic foot represents a major medical , social and economic problem worldwide.
Charcot's neuroarthropathy, being a common cause of diabetic foot, has been an intriguing topic of research for endocrinologists, podiatrists and surgeons. After its first description by JEAN-MARTIN CHARCOT in 1868, many theories have been put forward regarding its pathophysiology , but not much research has been done for its prevention and treatment , specially the inactive stage.
The course of Charcot 's neuroarthropathy is triphasic , with the diagnosis being usually missed in the active stage, henceforth the patients often come to us with a deformed foot. As a consequence , the osteoclastic activity in active stage renders the foot bones demineralized and weak, thus being susceptible to fracture and fragmentation.
Teriparatide is recombinant human (1-34) parathyroid molecule that has been approved for post-menopausal osteoporosis and in men with primary or secondary osteoporosis. It acts by preferentially stimulating osteoblast over osteoclast activity resulting in new bone formation and an increase in the rate of bone remodeling which manifest as an increase in skeletal mass and bone mineral density .
Keeping the pathophysiology of Charcot's foot in mind, teriparatide may be used as potential treatment for inactive Charcot's neuroarthropathy but there are no studies or randomized trials in this setting, till date. We hypothesize that teriparatide may increase the remodeling of foot bones in Charcot's neuroarthropathy, improve bone mineral density, subsequently leading to a reduction in the risk of fractures and progression of deformities. This study plans to compare the effects of teriparatide in diabetes patients with inactive Charcot's f
Detailed Summary:
Charcot neuroarthropathy (CN) was first described by Jean-Martin Charcot in a patient with tabes dorsalis who recognized that peripheral neuropathy could lead to neuropathic joints. This condition has many names, including Charcot osteoarthropathy, neuropathic osteo- arthropathy, and many others. Charcot foot may occur as a complication of neurosyphilis, syringomyelia, leprosy, poliomyelitis, congenital neuropathy and diabetes mellitus , the latter currently being the most common cause of CN. Since the description of CN in 1883, its pathophysiology remains an enigma, and there are no strict guidelines for the treatment of this disorder.
India has more people living with diabetes than any other country of the world and diabetic foot is one of the common diabetic complications found in India. The prevalence of Charcot foot in diabetes is not clearly known (0.1% to nearly 30%), but it is now appreciated that the condition is not as infrequent as might be generally thought. CN is characterized by progressive destruction of bones and joints of the foot with accompanying osteopenia. The current belief is that once the disease is triggered in a susceptible individual, it is mediated through a process of uncontrolled inflammation in the foot. This inflammation leads to osteolysis and is indirectly responsible for the progressive fracture and dislocation that characterizes its presentation.
The pathophysiologic event is cytokine- driven elevation of the receptor activator of nuclear factor kappa B ligand (RANKL), which, in turn, enhances the synthesis of nuclear factor kB (NF-kB). The latter promotes osteoclast maturation and osteoclastic activity, leading to osteoporosis in the affected bones. In parallel , NF-kB enhances the production of osteoprotegerin from osteoblasts, in order to provide an antagonist of RANKL and
Sponsor: Postgraduate Institute of Medical Education and Research
Current Primary Outcome: Remodeling of foot bones [ Time Frame: Two years ]
Original Primary Outcome: Efficacy of teriparatide in improving remodeling of foot bones in diabetic inactive Charcot's neuroarthropathy [ Time Frame: Two years ]
Current Secondary Outcome: Clinical events [ Time Frame: Two Years ]
Any of the following will be taken as a secondary end point:
- new onset fracture
- new onset/progression of deformity
- need of amputation
Original Secondary Outcome: Efficacy of teriparatide in improving remodeling of foot bones in diabetic inactive Charcot's neuroarthropathy [ Time Frame: two tears ]
Any of the following will be taken as a secondary end point:
- new onset fracture
- new onset/progression of deformity
- need of amputation
Information By: Postgraduate Institute of Medical Education and Research
Dates:
Date Received: December 23, 2013
Date Started: January 2014
Date Completion: December 2018
Last Updated: April 4, 2017
Last Verified: April 2017