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

Overview

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reuteri ATCC PTA 6475 (BioGaia® Gastrus) is currently the best possible formulation for optimal hydrolase activity (unpublished data from BioGaia® laboratory).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.

Interventions

• Dietary supplement Limosilactobacillus reuteri
  The BioGaia® Gastrus probiotic capsule contains the following components: L. reuteri DSM 17938, L. reuteri ATCC PTA 6475) at 10\^8 CFU\*/day, fully hydrogenated palm oil; ascorbic acid; tangerine flavour and mint flavour. \*Colony forming Unit
• Other Placebo
  The placebo capsules have the same external appearance and composition as the BioGaia® Gastrus Limosilactobacillus reuteri probiotic capsule (combination of L. reuteri DSM 17938 and L. reuteri ATCC PTA 6475), but without the active ingredient.

Primary outcome measures

• Chlordeconemia [Time frame: 6 months]

Secondary outcome measures (6)

• Chlordeconemia [Time frame: 3 months]
• Variation of chlordeconemia [Time frame: 6 months]
• concentration of CLD in the stool [Time frame: 6 months]
• Variation of chlordecone concentration in stool [Time frame: 6 months]
• Plasma total cholesterol concentrations [Time frame: 6 months]
• Clinical tolerance to BioGaia® Gastrus probiotic or placebo [Time frame: 6 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Martinique · 1 center

• Centre Hospitalier Universitaire de Martinique - Hôpital Pierre ZOBDA QUITMAN — Fort-de-France

Identifiers

NCT: NCT06026228 · 21_RIPH3-08 · 2021-A02293-38

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗