University Hospital Center of Martinique
Fort-de-France, 97261, France
Location status: Recruiting
NCT Number: NCT06365359
Chlordecone, an organochlorine pesticide, was widely used on banana farms in the French West Indies. Studies by Inserm and health authorities have confirmed the contamination of the food chain and the majority of the population of the French West Indies by chlordecone.
Epidemiological studies conducted in the French West Indies have shown that exposure to chlordecone at the levels observed is associated with an increased risk of developing several diseases, including premature birth and prostate cancer. Many of the adverse effects associated with chlordecone could be explained by its estrogenic hormonal properties, and systemic lupus erythematosus (SLE) is an autoimmune disease whose sensitivity to estrogen is well known and is reflected by 1) its clear predominance in women, 2) its predominance in women of childbearing age, 3) its risk of exacerbation in the event of pregnancy.
Chlordecone has the potential to modify the activity of SLE through mechanisms other than its pro-estrogenic effects. In rats, chlordecone was observed to induce alterations such as a reduction in lymphocyte count, thymic atrophy, and a decrease in splenic germinal centers and NK cells.
In a mouse model of systemic lupus erythematosus (SLE), exposure to chlordecone results in increased production of immune complexes and anti-DNA antibodies, which are markers of disease activity and monitoring.
Chlordecone also has a cellular effect that reduces the apoptosis of potentially auto-reactive lymphocytes and stimulates the production of GM-CSF, IL-2, TNF-alpha, and IFN-gamma. The latter is central to the pathophysiology of SLE. While experimental studies suggest a potential impact of chlordecone on SLE, no human studies have been conducted to date, and the chlordecone impregnation of lupus patients in Martinique remains unknown.
The most serious and feared complication of SLE is kidney damage. Kidney damage from the disease and the necessary immunosuppressive treatments can lead to significant morbidity and mortality, including death and end-stage chronic renal failure. Therefore, it is important to manage the disease carefully. Suspected lupus nephritis is confirmed by a renal biopsy, which allows for formal diagnosis and categorization into several classes. Suspected cases are identified by a proteinuria to creatininuria ratio greater than 0.5 g/g (or 24-hour proteinuria greater than 0.5g).
The objective of this project is to determine whether there is a positive association between lupus nephritis occurrence in patients followed by the internal medicine department of the Martinique University Hospital and organochlorine pesticide chlordecone impregnation.
Interested in participating?
Request Info18 year and older
All sexes
Observational
Fort-de-France, 97261, France
Location status: Recruiting
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
A 20 mL blood sample will be taken up to 6 months after inclusion of the patient for the analysis of chlordecone and the following organochlorine compounds: p,p'-DDE, βHCH, γHCH, PCB 153. This analysis will be carried out at the Institut Pasteur of Guadeloupe (IPG).
A 20 mL blood sample will be taken up to 6 months after inclusion of the patient for the cell collection which will be kept at the CeRBiM.
This collection will be used for subsequent studies on the immunotoxicity of chlordecone, by studying the cytokine, apoptotic and autoreactive functions of PBMC (Peripheral Blood Mononuclear Cells).
Time frame: 18 months
Calculation of the Odds ratio (OR) of having lupus kidney disease according to the plasma chlordecone concentration at baseline.
Patients classified "M+ = Suffering from lupus kidney disease" will be those for whom the diagnosis was suspected based on a proteinuria to creatininuria ratio greater than 0.5 g/g (or 24-hour proteinuria greater than 0.5g) and confirmed by a kidney biopsy which allows the formal diagnosis of lupus kidney damage, but also its categorization into several classes, depending on the cell proliferation observed.
The biomarker of exposure to chlordecone will, at a minimum, be dichotomized into two classes according to the median value of the distribution of plasma chlordecone concentration (E-/E+).
Time frame: 18 months
Average of SELENA-SLEDAI lupus activity score retrospectively assessed from diagnosis to patient inclusion + number of disease flares since the first diagnostic flare.
Time frame: 18 months
SLICC/SDI lupus after-effects score in the retrospective analysis of the history of the disease.
Time frame: 18 months
Distribution of plasma chlordecone concentration and of other organochlorine compounds such as: p,p'-DDE, βHCH, γHCH, PCB 153.
Time frame: 18 months
Distribution of plasma p,p'-DDE concentration
Time frame: 18 months
Distribution of plasma βHCH concentration
Time frame: 18 months
Distribution of plasma γHCH concentration
Time frame: 18 months
Distribution of plasma PCB 153 concentration
Contact information is provided by the study sponsor or research team.
University Hospital Center of Martinique
Other
Acronym: LUNEK
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