Clinical Trial: Genetic Contribution to the Pathophysiology of the Charcot Foot in Qatari Patients With Diabetes

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Genetic Contribution to the Pathophysiology of the Charcot Foot in Qatari Patients With Diabetes

Brief Summary: To assess the hypothesis that Charcot foot is associated with more vascular complications compared to matched diabetic patients without Charcot foot and to classify patients with Charcot foot according to the human genetic classification of the Qatari population.

Detailed Summary:

Diabetes is a serious health issue for the Qatari population since approximately 1/5 of the population has Type 2 Diabetes, which is 2-3 times higher than the world average. Although much of the clinical studies of diabetes often focused on microvascular phenotypes such as retinopathy and nephropathy, and macrovascular diseases presenting clinically as myocardial infarction, stroke, and peripheral vascular disease, other rare complications such as Charcot foot disease confer a significant burden in Qatar diabetic population, leading to decreased life quality.

Charcot foot is estimated to affect 0.8% to 8% of diabetic populations. It occurs most commonly in patients with diabetes complicated by severe peripheral neuropathy, often with coexisting sympathetic denervation, causing increased blood flow to the foot and increased bone resorption.

Uncontrolled and inappropriate inflammation leading to bone resorption and deformation has been the hallmark of diabetic Charcot foot pathophysiology. There are two major theories that provide the likely mechanism of the disease. The "neurovascular (French) theory" suggests that increased blood flow, as a result of autonomic neuropathy, can lead to bone destruction and mechanical debilitation. On the other hand, the "neurotraumatic (German) theory" argues that the loss of protective sensation leads to unperceived injury and trauma in the insensate foot. One can argue that the pathogenesis of Charcot neuro-arthropathy is most likely a combination of these processes. For unknown reasons, Charcot foot is trigged only in some susceptible individuals with diabetes.


Sponsor: Weill Medical College of Cornell University

Current Primary Outcome:

  • Assess the hypothesis that Charcot Foot is associated with more vascular complications compared to match diabetic patients without Charcot foot [ Time Frame: 6 months ]
  • Assess the hypothesis that Charcot foot disease reflects differences in monocyte epigenetics compared to other controls, particularly in genes involved in inflammation. [ Time Frame: 6 months ]
  • Assess the effect of initial methylation on kidney function in patients with type 2 diabetes mellitus, weather they have or not Charcot foot disease and for whom we have baseline kidney function, in a 2-year follow-up. [ Time Frame: 6 months ]
  • Assess the effect of improving diabetes control in patients with type 2 diabetes (Charcot foot and non-charcot foot patients) and a HBA1C >8.5% on total and gene-specific methylation. [ Time Frame: 6 months ]


Original Primary Outcome: Changes in DNA methylation and gene expression in blood monocytes and lymphocytes [ Time Frame: 1 hour ]

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Weill Medical College of Cornell University

Dates:
Date Received: December 9, 2014
Date Started: December 2013
Date Completion: December 2018
Last Updated: October 31, 2016
Last Verified: October 2016