xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06026228</url>
    </required_header>
    <id_info>
      <org_study_id>21_RIPH3-08</org_study_id>
      <secondary_id>2021-A02293-38</secondary_id>
      <nct_id>NCT06026228</nct_id>
    </id_info>
    <brief_title>Effects of Probiotic Oral Intake on Plasma Chlordecone (Kepone) Concentrations in Individuals Environmentally Exposed to Pesticide in Martinique.</brief_title>
    <acronym>CHLOR-DETOX</acronym>
    <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</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital Center of Martinique</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>BioGaia AB</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>University Hospital, Limoges</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Regional Health Agency, Martinique</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Biological Resource Centre, Martinique</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Clinical Research Vigilance Unit, University Hospital, Reims</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University Hospital Center of Martinique</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The CHLOR-DETOX study is a single-centre, double-blind, prospective, interventional,&#xD;
        controlled, exploratory pilot study on subjects environmentally exposed to the organochlorine&#xD;
        pesticide (kepone or chlordecone, CLD) in the French Caribbean (Martinique island). To our&#xD;
        best knowledge, it is the first clinical trial in such subjects evaluating the potential&#xD;
        effect of oral probiotic intake (Limosilactobacillus reuteri) on the reduction of CLD plasma&#xD;
        levels (chlordeconemia) and fecal excretion, thus concurring to the reduction of CLD toxicity&#xD;
        in study subjects.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The research question focuses on the ability of the probiotic Limosilactobacillus reuteri&#xD;
        Gastrus (combination of L. reuteri DSM 17938 and L. reuteri ATCC PTA 6475 from the BioGaia®&#xD;
        company) to reduce CLD toxicity in subjects exposed to this pesticide. In particular, we are&#xD;
        interested in whether the oral prescription of Limosilactobacillus reuteri reduces plasma&#xD;
        levels of CLD by increasing the fecal excretion of the deconjugated form of CLD. This&#xD;
        research hypothesis is based on the presence of a hydrolase activity (glucuronidase) in&#xD;
        Limosilactobacillus reuteri that allows the deconjugation of glucuronide derivatives (De&#xD;
        Boever et al 2000; Cardona et al. 2002; Martoni et al 2008). Limosilactobacillus reuteri is&#xD;
        the probiotic with the highest hydrolase activity. The combination of Limosilactobacillus&#xD;
        reuteri DSM 17938 and Limosilactobacillus reuteri ATCC PTA 6475 (BioGaia® Gastrus) is&#xD;
        currently the best possible formulation for optimal hydrolase activity (unpublished data from&#xD;
        BioGaia® laboratory). We also hypothesize that the increase in CLD elimination by the&#xD;
        digestive tract through the use of Limosilactobacillus reuteri avoids the appearance of side&#xD;
        effects encountered during the prolonged use of classical bile salt sequestrants (e.g.&#xD;
        QUESTAN).&#xD;
  &#xD;
        The effects of oral prescription of Limosilactobacillus reuteri on plasma levels and faecal&#xD;
        concentrations of CLD will be compared with a control group under placebo.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">May 2026</completion_date>
    <primary_completion_date type="Anticipated">October 2025</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>This is a study in two parallel groups of equal numbers: control group (placebo) and experimental group (probiotic).&#xD;
  The control group will receive daily a placebo capsule per os at mealtime (just before or after) for a period of 6 months.&#xD;
  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.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
      <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.&#xD;
  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.&#xD;
  Masking will be maintained throughout the study.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Chlordeconemia</measure>
      <time_frame>6 months</time_frame>
      <description>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)&#xD;
  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.&#xD;
  This relative variation will be calculated as the ratio of the difference in chlordeconemia T0 -T6mois to the initial chlordeconemia at T0.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Chlordeconemia</measure>
      <time_frame>3 months</time_frame>
      <description>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&#xD;
  The relative change in chlordeconemia between T0 and T3months will be compared between the BioGaia® Gastrus probiotic treated group and the placebo treated group.&#xD;
  This relative variation will be calculated as the ratio of the difference in chlordeconemia T0 -T3months to the initial chlordeconemia at T0.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Variation of chlordeconemia</measure>
      <time_frame>6 months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>concentration of CLD in the stool</measure>
      <time_frame>6 months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Variation of chlordecone concentration in stool</measure>
      <time_frame>6 months</time_frame>
      <description>- The relative change in stool CLD concentration from T0 to T6months within each patient group (probiotic group, placebo group) will be described</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma total cholesterol concentrations</measure>
      <time_frame>6 months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical tolerance to BioGaia® Gastrus probiotic or placebo</measure>
      <time_frame>6 months</time_frame>
      <description>Treatments will be assessed by adverse event reporting and based on a standardised and internationally recognised toxicity table for adults.&#xD;
  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 .</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Chlordecone (Kepone) Toxicity</condition>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>The control group will receive daily a placebo capsule per os at mealtime (just before or after) for a period of 6 months</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Experimental group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Limosilactobacillus reuteri</intervention_name>
      <description>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.&#xD;
  *Colony forming Unit</description>
      <arm_group_label>Experimental group</arm_group_label>
      <other_name>BioGaïa® Gastrus</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>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.</description>
      <arm_group_label>Control group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Male or female, 18 years of age or older&#xD;
  &#xD;
            -  Seen in clinical toxicology consultation at the CHU of Martinique during the study&#xD;
               period&#xD;
  &#xD;
            -  With an initial chlordeconemia &gt; 1μg/L on a test less than 1 month old at the time of&#xD;
               study inclusion&#xD;
  &#xD;
            -  Affiliated to a social security scheme&#xD;
  &#xD;
            -  Having received informed information on research&#xD;
  &#xD;
            -  Having freely given written and informed consent to participate in the research&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of cancer&#xD;
  &#xD;
            -  Recent infections less than 6 months old&#xD;
  &#xD;
            -  Known digestive diseases: chronic diarrhoea, ulcerative colitis, Crohn's disease,&#xD;
               pancreatitis&#xD;
  &#xD;
            -  Digestive procedures less than 6 months old.&#xD;
  &#xD;
            -  Intrahepatic cholestasis less than 6 months old&#xD;
  &#xD;
            -  Extrahepatic cholestasis less than 6 months old&#xD;
  &#xD;
            -  Use of cholestyramine or ursodeoxycholic acid in the previous 3 months&#xD;
  &#xD;
            -  Consumption of food (non-ordinary yoghurt, etc.) or supplements (tablets, drops,&#xD;
               capsules, etc.) containing L. reuteri or any other probiotic within the previous 2&#xD;
               weeks.&#xD;
  &#xD;
            -  Antibiotics taken in the previous 4 weeks.&#xD;
  &#xD;
            -  Immune deficiency secondary to a pathology (lymphoma, leukaemia) or medical treatment&#xD;
               (immunosuppressant, corticoid, chemotherapy).&#xD;
  &#xD;
            -  Women who are unable to obtain contraception during the trial&#xD;
  &#xD;
            -  Persons referred to in articles L.1121-5, L.1121-7, L. 1121-8 of the Public Health&#xD;
               Code:&#xD;
  &#xD;
                 -  Pregnant woman, parturient or breastfeeding mother&#xD;
  &#xD;
                 -  Adult subject to a legal protection measure (guardianship, curatorship, safeguard&#xD;
                    of justice)&#xD;
  &#xD;
                 -  Persons deprived of their liberty by a judicial or administrative decision,&#xD;
  &#xD;
                 -  Persons staying in a health or social care institution for purposes other than&#xD;
                    research&#xD;
  &#xD;
            -  Persons subject to psychiatric care under Articles L. 3212-1 and L. 3213-1 of the&#xD;
               Public Health Code.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>DABOR RESIERE, Professor</last_name>
      <role>Principal Investigator</role>
      <affiliation>University Hospital of Martinique</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>SEBASTIEN CAVALINI</last_name>
      <phone>+596 596 592 696</phone>
      <email>sebastien.cavalini@chu-martinique.fr</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>CORINE CARPIN</last_name>
      <phone>+596 596 592 696</phone>
      <email>corine.carpin@chu-martinique.fr</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Centre Hospitalier Universitaire de Martinique - Hôpital Pierre ZOBDA QUITMAN</name>
        <address>
          <city>Fort-de-France</city>
          <state>France</state>
          <zip>97261</zip>
          <country>Martinique</country>
        </address>
      </facility>
      <contact>
        <last_name>SEBASTIEN CAVALINI</last_name>
        <phone>+596 596 592 696</phone>
        <email>sebastien.cavalini@chu-martinique.fr</email>
      </contact>
      <contact_backup>
        <last_name>CORINE CARPIN</last_name>
        <phone>+596 596 592 696</phone>
        <email>corine.carpin@chu-martinique.fr</email>
      </contact_backup>
      <investigator>
        <last_name>Dabor RESIERE, Professor</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Martinique</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 30, 2023</study_first_submitted>
    <study_first_submitted_qc>August 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>August 30, 2023</last_update_submitted>
    <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Chlordecone toxicity</keyword>
    <keyword>Probiotics</keyword>
    <keyword>Gut elimination</keyword>
    <keyword>entero-hepatic cycle</keyword>
    <keyword>plasma level concentration</keyword>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06026228
  org study id: 21_RIPH3-08
  secondary id: 2021-A02293-38
  nct id: NCT06026228
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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, we 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). We 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.
  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.
  primary purpose: Treatment
  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.
  measure: Chlordeconemia
  time frame: 6 months
  description: 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.
  measure: Chlordeconemia
  time frame: 3 months
  description: 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.
  measure: Variation of chlordeconemia
  time frame: 6 months
  description: 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.
  measure: concentration of CLD in the stool
  time frame: 6 months
  description: 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.
  measure: Variation of chlordecone concentration in stool
  time frame: 6 months
  description: - The relative change in stool CLD concentration from T0 to T6months within each patient group (probiotic group, placebo group) will be described
  measure: Plasma total cholesterol concentrations
  time frame: 6 months
  description: 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.
  measure: Clinical tolerance to BioGaia® Gastrus probiotic or placebo
  time frame: 6 months
  description: 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 .
  arm group label: Control group
  arm group type: Placebo Comparator
  description: The control group will receive daily a placebo capsule per os at mealtime (just before or after) for a period of 6 months
  arm group label: Experimental group
  arm group type: Experimental
  description: 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
  intervention type: Dietary Supplement
  intervention name: Limosilactobacillus reuteri
  description: 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
  arm group label: Experimental group
  other name: BioGaïa® Gastrus
  intervention type: Other
  intervention name: Placebo
  description: 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.
  arm group label: Control group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: DABOR RESIERE, Professor
  role: Principal Investigator
  affiliation: University Hospital of Martinique
  last name: SEBASTIEN CAVALINI
  phone: +596 596 592 696
  email: sebastien.cavalini@chu-martinique.fr
  last name: CORINE CARPIN
  phone: +596 596 592 696
  email: corine.carpin@chu-martinique.fr
  facility: 
  contact: 
  contact backup: 
  investigator: 
  country: Martinique
  responsible party type: Sponsor
  sharing ipd: No