Adipose Tissue and Symptomatic Gonarthrosis (TAGS)

Comparative Study to Identify Biomarkers of Visceral Adipose Tissue Responsible for Symptomatic Gonarthrosis in Obese Patients

1. Prevalence of osteoarthritis in France Osteoarthritis (OA) is a very common disease, affecting almost 15% of the population. It is responsible for a significant socio-economic cost in connection with the chronic and disabling pain it causes . Gonarthrosis is the most frequently encountered arthritic localization . In a large 2010 meta-analysis, the main risk factors for developing knee OA were shown to be obesity, previous knee trauma, hand OA, female gender and advanced age. Smoking appeared to have a moderate protective effect . The risk of developing gonarthrosis in obese patients is 2.6 times higher than in the general population. Hypercholesterolemia itself is a risk factor for osteoarthritis, as are increased plasma levels of specific fatty acids and lipoproteins Inflammatory mechanism in osteoarthritis. Studies have shown that plasma levels of C-reactive protein, can be used to estimate individual susceptibility to developing osteoarthritis over a lifetime . In osteoarthritis patients, plasma concentrations of TNF-α, IL-6 and IL-1 are abnormally high, which appears to contribute to cartilage loss in these subjects .

3. Inflammatory mechanism in obesity. Obesity induces systemic and local joint mechanical stresses that increase the risk of developing gonarthrosis in obese or overweight individuals . Beyond the simple mechanical aspect, a body of evidence supports the assertion that obesity is responsible for a systemic inflammatory state, deleterious to joints. 1) Obesity is associated with radiographic and symptomatic osteoarthritis in non-weight-bearing joints, such as the hand In overweight and obese adults, plasma levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) are significantly increased .

3)Weight loss in obese subjects with osteoarthritis alleviates joint symptoms through reduced mechanical stress but also through reduced production and response of inflammatory products .

4. Common inflammatory mechanisms between adipose tissue and obesity. The relationship between adipose tissue and inflammation is complex given the different types of adipose tissue and the action of cells derived from it. Adipose tissue is an active endocrine organ composed of mature and developing adipocytes, as well as fibroblasts, endothelial cells and a wide range of immune cells, namely adipose tissue macrophages, neutrophils, eosinophils, mast cells, T cells and B cells. Adipose tissue is recognized as an endocrine organ that secretes a large number of inflammatory mediators, including cytokines (IL-1, IL-6, IL-8, TNF-α) and adipokines (leptin, adiponectin, resistin, visfatin). Communication between adipocytes and immune cells maintains tissue homeostasis. Obesity, however, can upset this balance.

Lipid metabolism and joint disorders have been shown to be linked . A high-fat diet may contribute to the development of osteoarthritis .

White and brown adipose tissue appear to play a complementary role in the development of osteoarthritis. Increased white adipose tissue in obesity is thought to create a systemic environment of increased inflammation through the release of pro-inflammatory cytokines and adipokines such as leptin and visfatin, all of which have been associated with osteoarthritis . Locally, white adipocytes in infra patellar adipose tissue are architecturally different in patients without gonarthrosis compared with those with knee osteoarthritis. This difference suggests that adipocyte gene expression is directly influenced by inflammation . In obese individuals, there is elevated IL-6 production in brown adipose tissue . Furthermore, it would appear that brown adipose tissue, unlike white, down-regulates the inflammatory profile of macrophages .

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity; Gonarthrosis
• Intervention / Treatment: Other: blood sampling; Other: knee radiography

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christian Roux; Phone Number: 0492039220; Email: roux.c2@chu-nice.fr
• Study Contact Backup: Name: Isa Costantini; Phone Number: 0492039220; Email: costantini.i@chu-nice.fr

Study Locations

• France
  • Nice, France, 06000
    • Nice University Hospital
    • Principal Investigator: Christian ROUX
    • Contact: Christian Roux; Phone Number: 0492039220; Email: roux.c2@chu-nice.fr
    • Contact: Isa Costantini; Phone Number: 0492039220; Email: constantini.i@chu-nice.fr
    • Sub-Investigator: Antonio Iannelli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients aged between 30 and 55.
• Patient with BMI > 40 or Patient with BMI between 35-40 and presence of hypertension and/or diabetes and/or obstructive sleep apnea syndrome.
• Patients scheduled for bypass or SLEEVE bariatric surgery.
• Patients with symptomatic gonarthrosis or patients with no signs of osteoarthritis.
• Patients who have given written consent following written and oral information.
• Patient affiliated to a social security scheme.

Exclusion Criteria:

• Patient having undergone knee ligamentoplasty.
• Patient with knee infiltration less than three months old.
• In the group of patients with no osteoarthritis, no known osteoarthritis or signs of osteoarthritis in a joint other than the knee.
• Patients treated with lipid-lowering or cholesterol-lowering drugs
• Postmenopausal patients
• Patient with weight change of more than 5% in the last 3 months
• Patients with known systemic inflammatory or autoimmune diseases
• Patients on special diets in the last 3 months (gluten-free, high-protein, low-carbohydrate diets)
• Patient with knee pain of secondary origin: tumor, inflammation, infection, fracture
• Patient with a contraindication to bariatric surgery
• Patient protected by law under guardianship or curatorship, or unable to participate in a clinical study under article L. 1121-16 of the French Public Health Code.
• Patient with insufficient command of the French language (assessed during interview).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: arthrose group	Other: blood sampling; blood sampling with analyses; Other: knee radiography; radiography of both knees in Schuss
Active Comparator: controle group	Other: blood sampling; blood sampling with analyses; Other: knee radiography; radiography of both knees in Schuss

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
lipolytic activity	glycerol dosage in mg/dL	baseline and perioperatively
lipolysis measurement	HSL dosage (%)	baseline and perioperatively

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2024
• Primary Completion (Estimated): June 15, 2025
• Study Completion (Estimated): November 15, 2025

Study Registration Dates

• First Submitted: March 1, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: 23-AOIP-02

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