Clinical trial NCT06026228: Effects of Probiotic Oral Intake on Plasma Chlordecone (Kepone) Concentrations in Individuals Environmentally Exposed to Pesticide in Martinique.
Official title: Effects of Oral Intake of the Probiotic Limosilactobacillus Reuteri on Plasma Chlordecone (Kepone) Concentrations (Chlordeconemia) in Individuals Environmentally Exposed to the Organochlorine Pesticide in Martinique : an Exploratory Pilot Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Chlordecone (Kepone) Toxicity
Keywords: Chlordecone toxicity
Probiotics
Gut elimination
entero-hepatic cycle
plasma level concentration
Lead sponsor: University Hospital Center of Martinique
Sponsor class: OTHER
Collaborators: name: BioGaia AB
name: University Hospital, Limoges
name: Regional Health Agency, Martinique
name: Biological Resource Centre, Martinique
name: Reims University hospital
First posted: 2023-09-07
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a study in two parallel groups of equal numbers: control group (placebo) and experimental group (probiotic).

The control group will receive daily a placebo capsule per os at mealtime (just before or after) for a period of 6 months.

The experimental group will receive daily per os one capsule of BioGaia® Gastrus probiotic , taken at mealtime (just before or after) for a period of 6 months.
Primary purpose: TREATMENT

Brief summary: The CHLOR-DETOX study is a single-centre, double-blind, prospective, interventional, controlled, exploratory pilot study on subjects environmentally exposed to the organochlorine pesticide (kepone or chlordecone, CLD) in the French Caribbean (Martinique island). To our best knowledge, it is the first clinical trial in such subjects evaluating the potential effect of oral probiotic intake (Limosilactobacillus reuteri) on the reduction of CLD plasma levels (chlordeconemia) and fecal excretion, thus concurring to the reduction of CLD toxicity in study subjects.

Detailed description: The research question focuses on the ability of the probiotic Limosilactobacillus reuteri Gastrus (combination of L. reuteri DSM 17938 and L. reuteri ATCC PTA 6475 from the BioGaia® company) to reduce CLD toxicity in subjects exposed to this pesticide. In particular, the investigators are interested in whether the oral prescription of Limosilactobacillus reuteri reduces plasma levels of CLD by increasing the fecal excretion of the deconjugated form of CLD. This research hypothesis is based on the presence of a hydrolase activity (glucuronidase) in Limosilactobacillus reuteri that allows the deconjugation of glucuronide derivatives (De Boever et al 2000; Cardona et al. 2002; Martoni et al 2008). Limosilactobacillus reuteri is the probiotic with the highest hydrolase activity. The combination of Limosilactobacillus reuteri DSM 17938 and Limosilactobacillus reuteri ATCC PTA 6475 (BioGaia® Gastrus) is currently the best possible formulation for optimal hydrolase activity (unpublished data from BioGaia® laboratory). The investigators also hypothesize that the increase in CLD elimination by the digestive tract through the use of Limosilactobacillus reuteri avoids the appearance of side effects encountered during the prolonged use of classical bile salt sequestrants (e.g. QUESTAN).

The effects of oral prescription of Limosilactobacillus reuteri on plasma levels and faecal concentrations of CLD will be compared with a control group under placebo.

Eligibility criteria: Inclusion Criteria:

* Male or female, 18 years of age or older
* Seen in clinical toxicology consultation at the CHU of Martinique during the study period
* With an initial chlordeconemia \> 1μg/L on a test less than 1 month old at the time of study inclusion
* Affiliated to a social security scheme
* Having received informed information on research
* Having freely given written and informed consent to participate in the research

Exclusion Criteria:

* History of cancer
* Recent infections less than 6 months old
* Known digestive diseases: chronic diarrhoea, ulcerative colitis, Crohn's disease, pancreatitis
* Digestive procedures less than 6 months old.
* Intrahepatic cholestasis less than 6 months old
* Extrahepatic cholestasis less than 6 months old
* Use of cholestyramine or ursodeoxycholic acid in the previous 3 months
* Consumption of food (non-ordinary yoghurt, etc.) or supplements (tablets, drops, capsules, etc.) containing L. reuteri or any other probiotic within the previous 2 weeks.
* Antibiotics taken in the previous 4 weeks.
* Immune deficiency secondary to a pathology (lymphoma, leukaemia) or medical treatment (immunosuppressant, corticoid, chemotherapy).
* Women who are unable to obtain contraception during the trial
* Persons referred to in articles L.1121-5, L.1121-7, L. 1121-8 of the Public Health Code:

  * Pregnant woman, parturient or breastfeeding mother
  * Adult subject to a legal protection measure (guardianship, curatorship, safeguard of justice)
  * Persons deprived of their liberty by a judicial or administrative decision,
  * Persons staying in a health or social care institution for purposes other than research
* Persons subject to psychiatric care under Articles L. 3212-1 and L. 3213-1 of the Public Health Code.

Primary outcomes:
measure: Chlordeconemia
timeFrame: 6 months
Secondary outcomes:
measure: Chlordeconemia
timeFrame: 3 months
measure: Variation of chlordeconemia
timeFrame: 6 months
measure: concentration of CLD in the stool
timeFrame: 6 months
measure: Variation of chlordecone concentration in stool
timeFrame: 6 months
measure: Plasma total cholesterol concentrations
timeFrame: 6 months
measure: Clinical tolerance to BioGaia® Gastrus probiotic or placebo
timeFrame: 6 months
Other outcomes:
Locations:
city: Fort-de-France
country: Martinique
facility: Centre Hospitalier Universitaire de Martinique - Hôpital Pierre ZOBDA QUITMAN
state: France
Study officials:
affiliation: University Hospital of Martinique
name: DABOR RESIERE, Professor
role: PRINCIPAL_INVESTIGATOR
References: