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 ]

20 diabetic patients , who are Vit.D and calcium sufficient , will be recruited and baseline serum urea, creatinine, calcium, inorganic phosphorus, Alkaline phosphatase, serum 25(OH)- Vit.D, and albumin level will be measured , along with serum iPTH (immunoreactive parathyroid hormone) level. They will undergo baseline X-ray, DEXA (Dual Energy X-Ray Absorptiometry) scan and F18 PET scan of foot with measurement of markers of bone turnover. 10 patients each will receive teriparatide or placebo for 18 months. They will be followed regularly at every 3 months with foot X-ray , serum urea , creatinine, calcium, albumin , inorganic phosphorus and alkaline phosphatase measurement. DEXA scan of foot bones will be done at 12 and 18 months , while F18 PET scan of foot and bone turnover markers will be measured at 3, 12 and 18 months after starting teriparatide therapy. Any side effect will be noted at each visit.


Original Primary Outcome: Efficacy of teriparatide in improving remodeling of foot bones in diabetic inactive Charcot's neuroarthropathy [ Time Frame: Two years ]

20 diabetic patients , who are Vit.D and calcium sufficient , will be recruited and baseline serum urea, creatinine, calcium, inorganic phosphorus, Alkaline phosphatase, serum 25(OH)- Vit.D, and albumin level will be measured , along with serum iPTH (immunoreactive parathyroid hormone) level. They will undergo baseline X-ray, DEXA (Dual Energy X-Ray Absorptiometry) scan and F18 PET scan of foot with measurement of markers of bone turnover. 10 patients each will receive teriparatide or placebo for 18 months. They will be followed regularly at every 3 months with foot X-ray , serum urea , creatinine, calcium, albumin , inorganic phosphorus and alkaline phosphatase measurement. DEXA scan of foot bones will be done at 12 and 18 months , while F18 PET scan of foot and bone turnover markers will be measured at 3, 12 and 18 months after starting teriparatide therapy. Any side effect will be noted at each visit.


Current Secondary Outcome: Clinical events [ Time Frame: Two Years ]

Any of the following will be taken as a secondary end point:

  1. new onset fracture
  2. new onset/progression of deformity
  3. 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:

  1. new onset fracture
  2. new onset/progression of deformity
  3. 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