NCT06314191: TAGS

Adipose Tissue and Symptomatic Gonarthrosis

Not yet recruiting NA Last updated 17 May 2024

What this trial tests

NA trial testing blood sampling in Gonarthrosis in 20 participants. Not yet recruiting.

Timeline

15 June 2024

Primary endpoint
15 June 2025

15 November 2025

Quick facts

Lead sponsor	Centre Hospitalier Universitaire de Nice
Phase	NA
Status	Not yet recruiting
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	basic science
Enrollment	20
Start date	15 June 2024
Primary completion	15 June 2025
Estimated completion	15 November 2025
Sites	1 location across France

Drugs / interventions tested

• blood sampling — full drug profile →
• knee radiography

Conditions studied

• Gonarthrosis — all drugs for Gonarthrosis →
• Obesity — all drugs for Obesity →

Sponsor

Centre Hospitalier Universitaire de Nice

Who can join

Adults 30 to 55, any sex, with Gonarthrosis or Obesity. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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 .

Publications & conference data

No peer-reviewed publications indexed yet for this trial.