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

NCT ID: NCT02316483

Last Updated: 2020-01-14

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 57 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2019-12-31

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 Description

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.

Conditions

Charcot Arthropathy; Type 2 Diabetes

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Group I: T2D and Charcot foot

Individuals with confirmed diagnosis of type 2 diabetes, using the American Diabetes Association guidelines and confirmed diagnosis of Charcot foot, based on clinical and radiological evidence of Charcot foot.

No interventions assigned to this group

Group II: T2D neuropathy, no charcot

Individuals with type 2 diabetes and presence of neuropathy but the absence of Charcot foot.

No interventions assigned to this group

Group III: Control, non-diabetic

Individuals without history of type 2 diabetes.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

1. Must provide informed consent

2. Must hold Qatari passport

3. Males or Females ages 30 years or older to minimize the potential confounding contribution of other forms of diabetes mellitus

4. In patients with Diabetes, no concomitant diseases except for micro- and macrovascular complications of diabetes (nephropathy, retinopathy, peripheral arterial disease, coronary artery disease, neuropathy) or symptoms of the metabolic syndrome (hypertension, dyslipidemia and obesity).

5. Not taking any chronic medications (except of the diabetes, cardiovascular related drugs, anti-inflammatory drugs and/or any other treatment used for Charcot foot).

Exclusion Criteria

1. Other forms of diabetes (Type I, MODY, secondary diabetes)

2. Active pregnancy

3. Active infection or acute illness of any kind (except for Charcot foot)

4. Chronic inflammation (auto-immune diseases) or infection

5. Evidence of malignancy within the past 5 years

6. Chronic hematological disorders known to affect HBA1C results such as hemoglobinopathies (e.g., sickle cell disease and thalassemia), increased red-cell turnover (e.g., hemolytic anemia and spherocytosis)

7. Acute or critical limb ischemia.

8. Osteomyelitis

9. History of recent (within 6 months) immunosuppressive treatment including corticosteroids and anti-TNF-alpha compounds.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hamad Medical Corporation

INDUSTRY

Sponsor Role: collaborator

Weill Cornell Medical College in Qatar

OTHER

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charbel Abi Khalil, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Cornell Medical College in Qatar

Locations

Hamad Medical Corporation

Doha, , Qatar

Countries

Qatar

References

Pasquier J, Ramachandran V, Abu-Qaoud MR, Thomas B, Benurwar MJ, Chidiac O, Hoarau-Vechot J, Robay A, Fakhro K, Menzies RA, Jayyousi A, Zirie M, Al Suwaidi J, Malik RA, Talal TK, Najafi-Shoushtari SH, Rafii A, Abi Khalil C. Differentially expressed circulating microRNAs in the development of acute diabetic Charcot foot. Epigenomics. 2018 Oct;10(10):1267-1278. doi: 10.2217/epi-2018-0052. Epub 2018 Jun 5.

Reference Type: DERIVED

PMID: 29869523 (View on PubMed)

Other Identifiers

13-00031 [JIRB]

Identifier Type: -

Identifier Source: org_study_id