Clinical trial NCT06365359: Systemic Lupus Erythematosus and Chlordecone Impregnation in Martinique
Official title: Systemic Lupus Erythematosus and Chlordecone Impregnation in Martinique
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Systemic Lupus Erythematosus
Renal Disease
Keywords: Systemic Lupus Erythematosus
Chlordecone impregnation
Organochlorine pesticide (chlordecone, p,p'-DDE, βHCH, γHCH, PCB 153)
Renal Disease
Lead sponsor: University Hospital Center of Martinique
Sponsor class: OTHER
Collaborators: name: Institut Pasteur de Guadeloupe
name: Centre de Ressources Biologiques de la Martinique (CeRBiM)
First posted: 2024-04-15
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with systemic lupus erythematosus according to the ACR 1997 or ACR/EULAR 2019 criteria

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Patients with systemic lupus erythematosus according to the ACR 1997 or ACR/EULAR 2019 criteria,
* Present in the active line of the internal medicine department of the Martinique University Hospital since 2005,
* Whose illness has been progressing for at least 3 years,
* Living in Martinique or Guadeloupe for at least 1 year,
* Patients who have given their free, informed and written consent.

Exclusion Criteria:

* Patients for whom kidney disease cannot be authenticated or ruled out (refusal, contraindication or impossibility of renal biopsy),
* Patients without social security coverage,
* Current legal protection,
* Patients who have not given their consent to the use of their data,
* Pregnant or breastfeeding women.

Primary outcomes:
measure: To estimate the risk of presenting a renal complication of lupus disease based on the level of impregnation with chlordecone in the lupus patients seen at the Martinique University Hospital.
timeFrame: 18 months
Secondary outcomes:
measure: To compare the activity of lupus according to the level of impregnation with chlordecone.
timeFrame: 18 months
measure: To compare the after-effects of lupus according to the level of impregnation with chlordecone.
timeFrame: 18 months
measure: To describe the distribution of the plasma concentration of chlordecone in lupus patients followed by the internal medicine department of the Martinique University Hospital.
timeFrame: 18 months
measure: To describe the distribution of the plasma concentration of p,p'-DDE in lupus patients followed by the internal medicine department of the Martinique University Hospital.
timeFrame: 18 months
measure: To describe the distribution of the plasma concentration of βHCH in lupus patients followed by the internal medicine department of the Martinique University Hospital.
timeFrame: 18 months
measure: To describe the distribution of the plasma concentration of γHCH in lupus patients followed by the internal medicine department of the Martinique University Hospital.
timeFrame: 18 months
measure: To describe the distribution of the plasma concentration of PCB 153 in lupus patients followed by the internal medicine department of the Martinique University Hospital.
timeFrame: 18 months
Other outcomes:
Locations:
city: Fort-de-France
country: France
facility: University Hospital Center of Martinique
Study officials:
affiliation: University Hospital Center of Martinique
name: Benoît SUZON, PhD
role: PRINCIPAL_INVESTIGATOR
References: