Effects of Probiotic Oral Intake on Plasma Chlordecone (Kepone) Concentrations in Individuals Environmentally Exposed to Pesticide in Martinique. (CHLOR-DETOX)

• ClinicalTrials.gov Identifier: NCT06026228
• Recruitment Status: Not yet recruiting
• First Posted: September 7, 2023
• Last Update Posted: February 21, 2024
• Sponsor: University Hospital Center of Martinique
• Collaborators: BioGaia AB; University Hospital, Limoges; Regional Health Agency, Martinique; Biological Resource Centre, Martinique; Reims University Hospital
• Information provided by (Responsible Party): University Hospital Center of Martinique

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Chlordecone (Kepone) Toxicity	Dietary Supplement: Limosilactobacillus reuteri; Other: Placebo	Not Applicable

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reuteri ATCC PTA 6475 (BioGaia® Gastrus) is currently the best possible formulation for optimal hydrolase activity (unpublished data from BioGaia® laboratory).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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

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.

• Masking: Triple (Participant, Investigator, Outcomes Assessor)

Masking Description

Masking will be carried out by the hospital pharmacy, which will dispense the appropriate batches to the team, following the randomisation list established by the Methodology and Data Management Centre.

The hospital pharmacy, will keep a batch matching table, which will be made available to the vigilance unit and the Methodology and Data Management Centre.

Masking will be maintained throughout the study.

• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: April 2024
• Estimated Primary Completion Date: April 2026
• Estimated Study Completion Date: October 2026

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Control group; The control group will receive daily a placebo capsule per os at mealtime (just before or after) for a period of 6 months	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.
Experimental: Experimental group; The experimental group will receive daily per os one capsule of BioGaia® Gastrus probiotic (combination of L. reuteri DSM 17938 and L. reuteri ATCC PTA 6475) dosed at 108 colony forming units (CFU)/day (distributed by the laboratory PEDIACT France), taken at mealtime (just before or after) for a period of 6 months	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 Name: BioGaïa® Gastrus

Outcome Measures

Primary Outcome Measures :

1. Chlordeconemia [ Time Frame: 6 months ]

   Chlordeconemia measured by a gas chromatography/mass spectrometry (GC/MS) technique expressed in μg/L (analytical detection limit LDD of 0.05 μg/L - quantification limit LDQ of 0.1 μg/L)

   The relative change in chlordeconemia between T0 and T6 months will be compared between the group of patients treated with the BioGaia® Gastrus probiotic and the group of patients treated with placebo.

   This relative variation will be calculated as the ratio of the difference in chlordeconemia T0 -T6mois to the initial chlordeconemia at T0.

Secondary Outcome Measures :

1. Chlordeconemia [ Time Frame: 3 months ]

   Chlordeconemia measured by a gas chromatography/mass spectrometry (GC/MS) technique expressed in μg/L (analytical detection limit LDD of 0.05 μg/L - quantification limit LDQ of 0.1 μg/L

   The relative change in chlordeconemia between T0 and T3months will be compared between the BioGaia® Gastrus probiotic treated group and the placebo treated group.

   This relative variation will be calculated as the ratio of the difference in chlordeconemia T0 -T3months to the initial chlordeconemia at T0.

2. Variation of chlordeconemia [ Time Frame: 6 months ]
   The relative variation of chlordeconemia from T0 to T6 months in each group of patients (probiotic group, placebo group) will be described. The plasma half-life values of CLD, expressed in months, will be determined for each group.
3. concentration of CLD in the stool [ Time Frame: 6 months ]
   The concentration of CLD in the stool at 3 months (T3 months) and 6 months (T6 months) will be measured using the same method described in the primary outcome (GC/MS technique). The relative changes in stool CLD concentration between T0 and T3mois and T0 and T6mois will be compared between the BioGaia® Gastrus probiotic treated group and the placebo treated group.
4. Variation of chlordecone concentration in stool [ Time Frame: 6 months ]
   - The relative change in stool CLD concentration from T0 to T6months within each patient group (probiotic group, placebo group) will be described
5. Plasma total cholesterol concentrations [ Time Frame: 6 months ]
   Plasma total cholesterol concentrations, measured by the reference technique (ultracentrifugation followed by heparin-manganese precipitation and then quantification by the Abell-Kendall method) at T0 , T3 months and T6 months will be described. The relative variations of plasma total cholesterol concentrations between T0 and T3months and T0 and T6months will be compared between the group of patients treated with the BioGaia® Gastrus probiotic and the group of patients treated with placebo.
6. Clinical tolerance to BioGaia® Gastrus probiotic or placebo [ Time Frame: 6 months ]

   Treatments will be assessed by adverse event reporting and based on a standardised and internationally recognised toxicity table for adults.

   This tolerance will be assessed by a telephone interview at T1 month, T2 months, T4 months and T5 months, as well as during face-to-face follow-up visits at T3months and T6months .

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: SEBASTIEN CAVALINI; +596 596 592 696; sebastien.cavalini@chu-martinique.fr

Contact: CORINE CARPIN; +596 596 592 696; corine.carpin@chu-martinique.fr

Locations

Martinique

Centre Hospitalier Universitaire de Martinique - Hôpital Pierre ZOBDA QUITMAN

Fort-de-France, France, Martinique, 97261

Contact: SEBASTIEN CAVALINI +596 596 592 696 sebastien.cavalini@chu-martinique.fr

Contact: CORINE CARPIN +596 596 592 696 corine.carpin@chu-martinique.fr

Principal Investigator: Dabor RESIERE, Professor

Sponsors and Collaborators

University Hospital Center of Martinique

BioGaia AB

University Hospital, Limoges

Regional Health Agency, Martinique

Biological Resource Centre, Martinique

Reims University Hospital

Investigators

• Principal Investigator: DABOR RESIERE, Professor; University Hospital of Martinique

More Information

• Responsible Party: University Hospital Center of Martinique
• ClinicalTrials.gov Identifier: NCT06026228
• Other Study ID Numbers: 21_RIPH3-08; 2021-A02293-38 ( Other Identifier: French National Medicines and Health Products safety Agency )
• First Posted: September 7, 2023
• Last Update Posted: February 21, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital Center of Martinique:

Chlordecone toxicity; Probiotics; Gut elimination; entero-hepatic cycle; plasma level concentration