Risk Factor Analysis for Charcot Foot in Patients With Diabetes Mellitus: The Interplay of Inflammatory Cytokines and Metabolic Factors

NCT ID: NCT07139184

Last Updated: 2025-08-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-10-31

Study Completion Date

2027-10-31

Brief Summary

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Diabetes mellitus (DM) is among the most common metabolic disorders globally. According to the data from international research, the number of persons with diabetes mellitus reached 366 million in 2011 and is predicted to increase to 552 million by 2030.

Detailed Description

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Hyperglycaemia is a hallmark of diabetes mellitus resulting from defects in insulin secretion, insulin action, or both. Diabetes-related chronic hyperglycaemia is linked to long-term harm complications and failure of several organs, particularly the heart, blood vessels, kidneys, eyes, and nerves and even the musculoskeletal system Charcot neuroarthropathy, is a condition that develops in people with diabetes and neuropathy, causing damage to the bones and joints in the foot There are several risk factors for developing Charcot foot in patients with DM, such as age, gender, duration of diabetes mellitus, blood pressure, blood lipid levels, smoking, and levels of HbA1c. However, little is known about the most significant risk factor to develop such debilitating Charcot foot disease.

Acute Charcot arthritis is also characterized by a marked inflammatory response. Several chronic pro-inflammatory markers are elevated in affected individuals including interleukin-1β, interleukin 6, and tumour necrosis factor-α, and increased receptor activation of nuclear factor-K β ligand, which is imbalanced with its receptor and osteoprotegerin.

Interleukin-10 (IL-10) is a multifunctional cytokine that plays a key role in controlling inflammation and preserving cellular balance. Its primary function is anti-inflammatory, helping to prevent excessive immune reactions by acting mainly through the Jak1/Tyk2 and STAT3 signaling pathway. However, IL-10 can also act as an immune activator under certain conditions, showing stimulatory effects that support immune responses in specific conditions. Given the pivotal role of IL-10 in immune modulation, this cytokine could have relevant implications in pathologies characterized by hyperinflammatory state such as Charcot foot disease.

TNF-α is a member of the vast cytokine family being considered a proinflammatory substance produced many by macrophages and other cells belonging to the innate immunity, many of them classified as indeed Antigen Presenting Cells (APCs) involved in the complex chemotactic process of activation of the adaptive immunity. Elevated levels of TNF-α have been implicated in the development and progression of various neuropathies, including those associated with diabetes.

Although Charcot foot disease is a frequent complication of diabetic neuropathy, less is known about the possibility of its early prevention. This research aims to highlight potentially important early identifiable biomarkers that can lead to Charcot foot disease in patients with DM.

Conditions

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Charcot Foot

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

RETROSPECTIVE

Study Groups

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The case group: (30 cases)

is comprised of patients with diabetes mellitus suffering from Charcot foot and diagnosed clinically.

Diagnosis of Charcot foot disease

Intervention Type DIAGNOSTIC_TEST

Diagnosis of Charcot foot disease will be obtained from the results of physical examination and according to x-ray examination of foot which was performed at the Radiology Department of Assiut University Hospital. The Eichenholtz classification system, developed by Sidney N. Eichenholtz in 1966, categorizes Charcot arthropathy (also known as Charcot foot) into three stages based on clinical and radiographic findings. These stages are development, coalescence, and reconstruction

Hematologic and biochemical parameters,

Intervention Type DIAGNOSTIC_TEST

Hematologic and biochemical parameters, including lymphocyte, monocyte, neutrophil, and platelet counts, as well as glucose, HbA1c, triglyceride (TG), HDL, and LDL levels, will be extracted from patient records.

NLR=absolute neutrophil count (109/L)/absolute lymphocyte count (109/L), PLR=platelet count (109/L)/absolute lymphocyte count (109/L), LMR=absolute lymphocyte count (109/L)/absolute monocyte count (109/L), GLR=glucose (mg/dL)/absolute lymphocyte ratio (109/L), TGR=triglyceride (mg/dL)/glucose ratio (mg/dL), THR=triglyceride (mg/dL)/HDL ratio (mg/dL), SIRI = absolute neutrophil count (109/L) × absolute monocyte count (109/L)/ absolute lymphocyte count (109/L), SII = platelet count (109/L) × absolute monocyte count (109/L)/absolute lymphocyte count (109/L), TyG index = fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2, PIV =absolute neutrophil count (109/L) × platelet count (109/L) × absolute monocyte count (109/L)/absolute lymphocyte count (109/L).

ELIZA Assay

Intervention Type DIAGNOSTIC_TEST

For each patient, 2 ml of blood will be obtained. The serum levels of IL-10, TNF-α will be assessed by using (ELISA) kit obtained from (Biodiagnostic company, Egypt) according to the manufacturer protocol.

The control group: (30 cases)

is comprised DM patients without Charcot foot.

Hematologic and biochemical parameters,

Intervention Type DIAGNOSTIC_TEST

Hematologic and biochemical parameters, including lymphocyte, monocyte, neutrophil, and platelet counts, as well as glucose, HbA1c, triglyceride (TG), HDL, and LDL levels, will be extracted from patient records.

NLR=absolute neutrophil count (109/L)/absolute lymphocyte count (109/L), PLR=platelet count (109/L)/absolute lymphocyte count (109/L), LMR=absolute lymphocyte count (109/L)/absolute monocyte count (109/L), GLR=glucose (mg/dL)/absolute lymphocyte ratio (109/L), TGR=triglyceride (mg/dL)/glucose ratio (mg/dL), THR=triglyceride (mg/dL)/HDL ratio (mg/dL), SIRI = absolute neutrophil count (109/L) × absolute monocyte count (109/L)/ absolute lymphocyte count (109/L), SII = platelet count (109/L) × absolute monocyte count (109/L)/absolute lymphocyte count (109/L), TyG index = fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2, PIV =absolute neutrophil count (109/L) × platelet count (109/L) × absolute monocyte count (109/L)/absolute lymphocyte count (109/L).

ELIZA Assay

Intervention Type DIAGNOSTIC_TEST

For each patient, 2 ml of blood will be obtained. The serum levels of IL-10, TNF-α will be assessed by using (ELISA) kit obtained from (Biodiagnostic company, Egypt) according to the manufacturer protocol.

Interventions

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Diagnosis of Charcot foot disease

Diagnosis of Charcot foot disease will be obtained from the results of physical examination and according to x-ray examination of foot which was performed at the Radiology Department of Assiut University Hospital. The Eichenholtz classification system, developed by Sidney N. Eichenholtz in 1966, categorizes Charcot arthropathy (also known as Charcot foot) into three stages based on clinical and radiographic findings. These stages are development, coalescence, and reconstruction

Intervention Type DIAGNOSTIC_TEST

Hematologic and biochemical parameters,

Hematologic and biochemical parameters, including lymphocyte, monocyte, neutrophil, and platelet counts, as well as glucose, HbA1c, triglyceride (TG), HDL, and LDL levels, will be extracted from patient records.

NLR=absolute neutrophil count (109/L)/absolute lymphocyte count (109/L), PLR=platelet count (109/L)/absolute lymphocyte count (109/L), LMR=absolute lymphocyte count (109/L)/absolute monocyte count (109/L), GLR=glucose (mg/dL)/absolute lymphocyte ratio (109/L), TGR=triglyceride (mg/dL)/glucose ratio (mg/dL), THR=triglyceride (mg/dL)/HDL ratio (mg/dL), SIRI = absolute neutrophil count (109/L) × absolute monocyte count (109/L)/ absolute lymphocyte count (109/L), SII = platelet count (109/L) × absolute monocyte count (109/L)/absolute lymphocyte count (109/L), TyG index = fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2, PIV =absolute neutrophil count (109/L) × platelet count (109/L) × absolute monocyte count (109/L)/absolute lymphocyte count (109/L).

Intervention Type DIAGNOSTIC_TEST

ELIZA Assay

For each patient, 2 ml of blood will be obtained. The serum levels of IL-10, TNF-α will be assessed by using (ELISA) kit obtained from (Biodiagnostic company, Egypt) according to the manufacturer protocol.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Adult Patients who are diagnosed with DM who are willing to participate in the study with informed consent form.

Exclusion Criteria

* Patients with neuritis / neuropathy of the lower extremity due to other causes other than DM
* Significant trauma that may cause peripheral nerve damage.
* Patient with routine use of corticosteroid
* Previous history of smoking
* Patients with chronic renal impairment due to diseases other than DM (creatinine \> 1.4 mg/dL), previous myocardial infarction or stroke, history of cancer.
* Patients with iron deficiency anemia or uremia affecting HbA1c levels or elevated triglyceride or bilirubin levels.
* Patients diagnosed with neurological disease, malignancy.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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Amr Mohamed Ali Mohamed

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

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Dr. Refaat Fathy Abdel-Aal Naseer, Prof

Role: CONTACT

+201011121526

Mohammed Hasan Mohammed AbdEllah-Alawi, Dr.

Role: CONTACT

+201115353591

References

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Roglic G. WHO Global report on diabetes: A summary. International Journal of Noncommunicable Diseases. 2016;1(1):3-8.

Reference Type BACKGROUND

Silva LB, dos Santos Neto AP, Maia SMAS, dos Santos Guimarães C, Quidute IL, Carvalho AdAT, et al. The Role of TNF-α as a Proinflammatory Cytokine in Pathological Processes. The Open Dentistry Journal. 2019;13:332-8.

Reference Type BACKGROUND

Pratistha I, Kawiyana K, Aryana W. Duration of Type II DM, HbA1C Levels, TNF-α and IL-10 as Risk Factors for Level Charcot Joint Foot and Ankle in Type II DM Patients. International Journal of Health Sciences and Research. 2022;12:147-56.

Reference Type BACKGROUND

Uslu MF, Yilmaz M. Are Inflammatory Markers Important for Assessing the Severity of Diabetic Polyneuropathy? Medicina (Kaunas). 2025 Feb 25;61(3):400. doi: 10.3390/medicina61030400.

Reference Type BACKGROUND
PMID: 40142211 (View on PubMed)

Rosenbaum AJ, DiPreta JA. Classifications in brief: Eichenholtz classification of Charcot arthropathy. Clin Orthop Relat Res. 2015 Mar;473(3):1168-71. doi: 10.1007/s11999-014-4059-y. Epub 2014 Nov 21. No abstract available.

Reference Type BACKGROUND
PMID: 25413713 (View on PubMed)

Garcia-Dominguez M. The Role of TNF-alpha in Neuropathic Pain: An Immunotherapeutic Perspective. Life (Basel). 2025 May 14;15(5):785. doi: 10.3390/life15050785.

Reference Type BACKGROUND
PMID: 40430212 (View on PubMed)

Carlini V, Noonan DM, Abdalalem E, Goletti D, Sansone C, Calabrone L, Albini A. The multifaceted nature of IL-10: regulation, role in immunological homeostasis and its relevance to cancer, COVID-19 and post-COVID conditions. Front Immunol. 2023 Jun 8;14:1161067. doi: 10.3389/fimmu.2023.1161067. eCollection 2023.

Reference Type BACKGROUND
PMID: 37359549 (View on PubMed)

Bobirca A, Musetescu AE, Bordianu A, Pantea Stoian A, Salmen T, Marinescu DC, Alexandru C, Florescu A, Radu R, Isac S, Patrascu T, Serban D, Bobirca F. Novel Biomarkers Predictive of Diabetic Charcot Foot-An Overview of the Literature. Life (Basel). 2022 Nov 21;12(11):1944. doi: 10.3390/life12111944.

Reference Type BACKGROUND
PMID: 36431079 (View on PubMed)

Schmidt BM. Clinical insights into Charcot foot. Best Pract Res Clin Rheumatol. 2020 Jun;34(3):101563. doi: 10.1016/j.berh.2020.101563. Epub 2020 Jul 5.

Reference Type BACKGROUND
PMID: 32641254 (View on PubMed)

Dardari D. An overview of Charcot's neuroarthropathy. J Clin Transl Endocrinol. 2020 Oct 28;22:100239. doi: 10.1016/j.jcte.2020.100239. eCollection 2020 Dec.

Reference Type BACKGROUND
PMID: 33251117 (View on PubMed)

Casadei G, Filippini M, Brognara L. Glycated Hemoglobin (HbA1c) as a Biomarker for Diabetic Foot Peripheral Neuropathy. Diseases. 2021 Feb 22;9(1):16. doi: 10.3390/diseases9010016.

Reference Type BACKGROUND
PMID: 33671807 (View on PubMed)

Wukich DK, Schaper NC, Gooday C, Bal A, Bem R, Chhabra A, Hastings M, Holmes C, Petrova NL, Santini Araujo MG, Senneville E, Raspovic KM. Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus (IWGDF 2023). Diabetes Metab Res Rev. 2024 Mar;40(3):e3646. doi: 10.1002/dmrr.3646. Epub 2023 May 23.

Reference Type BACKGROUND
PMID: 37218537 (View on PubMed)

Farmaki P, Damaskos C, Garmpis N, Garmpi A, Savvanis S, Diamantis E. Complications of the Type 2 Diabetes Mellitus. Curr Cardiol Rev. 2020;16(4):249-251. doi: 10.2174/1573403X1604201229115531. No abstract available.

Reference Type BACKGROUND
PMID: 33407062 (View on PubMed)

Other Identifiers

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AMAAmrMohammedAli

Identifier Type: -

Identifier Source: org_study_id

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