Exome Evaluation in Patients Living With Diabetes Complicated by Charcot Neuroarthropathy. (CHARCOTEX)

Diabetes, like obesity, has reached worldwide proportions such that we're talking about a pandemic. These two diseases are a major cause of mortality and multiple complications. The medical and financial stakes involved make these two diseases a major public health issue. Two groups of factors contribute to these diseases: the environment and genetics. The use of next-generation sequencing (NGS) is a highly relevant tool for identifying mutations in already known genes, or new genes involved in the disease, for diagnostic purposes. This approach makes it possible to validate previously described genes and/or discover new loci linked to new signalling pathways involved in the pathophysiology of Charcot's foot in patients with diabetes

Study Overview

• Status: Not yet recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Other: bood sample

Detailed Description

In patients living with diabetes, a rare and devastating joint complication known as Charcot's neuroarthropathy (CN) has been observed. The clinical presentation of this complication is characterized by activation of inflammation and bone remodeling markers, disruption of the osteoblast and osteoclast system, activation of the RANKL (Receptor activator of nuclear factor-kappa B ligand) system and its antagonist osteoprotegerin (OPG), and often a fatigue fracture due to physical activity.

The pathogenic mechanisms of CN have been the subject of much debate, and there are a number of competing theories which are not necessarily exclusive.

CN patients have been shown to have reduced bone density in the lower limbs compared with neuropathic subjects. Studies using bone markers to assess bone formation and resorption demonstrated that there is an increase in osteoclastic activity relative to osteoblastic activity in both acute and chronic forms of CN. In 2007, W.J. Jeffcoate described CN as an increased inflammatory response to injury inducing increased bone lysis. Since the emergence of this theory, a significant number of studies have evaluated inflammatory factors and bone modeling in patients with CN, such as C-reactive protein, TNF α and IL6. Three studies showed an increase in their levels in the setting of CN.

otherwise known genes, or new genes implicated in the disease, for diagnostic purposes This approach makes it possible to validate previously described genes and/or discover new loci linked to new signalling pathways involved in the pathophysiology of Charcot's foot in patients with diabetes.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Caroline TOURTE; Phone Number: 01 61 69 31 50; Email: caroline.tourte@chsf.fr
• Study Contact Backup: Name: Dured DARDARI, MD; Phone Number: 01 61 69 40 17; Email: dured.dardari@chsf.fr

Study Locations

• France
  • Corbeil-essonnes Cedex, France, 91106
    • Centre Hospitalier Sud Francilien
    • Contact: Dured DARDARI; Phone Number: 0161694017; Email: dured.dardari@chsf.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patiens living with type 2 diabetes complicates by Charcot Neuroarthopathy

Description

Inclusion Criteria:

• Men or women aged 18 to 70
• with type 2 diabetes for at least one year
• with active or chronic Charcot neuroarthropathy (Group 1) OR
• never had Charcot neuroarthropathy (Group 2)
• Have agreed to participate in the study and have signed an informed consent form.

Exclusion Criteria:

- Subject under guardianship or curatorship.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; patients with type 2 diabetes complicated by active or chronic Charcot neuropathy	Other: bood sample; Exome measurements
Group 2; patients living with type 2 diabetes without active or chronic Charcot neuroarthropathy.	Other: bood sample; Exome measurements

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
exom	Exome measurement at the time of inclusion (D0) via a differential statistical analysis of the "burden" type aimed at comparing the organization of the mutational load between the two study groups	at day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
exome variations	Identification of "Group1" specific candidate variant(s)/gene(s)	at day 0

Collaborators and Investigators

• Sponsor: Centre Hospitalier Sud Francilien

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): May 28, 2025
• Study Completion (Estimated): May 28, 2025

Study Registration Dates

• First Submitted: October 16, 2023
• First Submitted That Met QC Criteria: October 20, 2023
• First Posted (Actual): October 24, 2023

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Exome; type 2 Diabetes; CHARCOT neuroarthropathy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 2023/0025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No