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/NCT05966727</url>
    </required_header>
    <id_info>
      <org_study_id>21-AOI-07</org_study_id>
      <nct_id>NCT05966727</nct_id>
    </id_info>
    <brief_title>Exploratory Evaluation of the Effect of Cholestyramine on Serum Levels of POPs in Obese Female Patients</brief_title>
    <acronym>OBESE</acronym>
    <official_title>Exploratory Evaluation of the Effect of Cholestyramine on Serum Levels of Persistent Organic Pollutants in Obese Female Patients - OBESE (OBesity, cholEStyramine, womEn)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Centre Hospitalier Universitaire de Nice</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Centre Hospitalier Universitaire de Nice</source>
    <oversight_info>
      <has_dmc>No</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>
        Environmental endocrine disruptors (EDCs) represent a major problem for human health.Some&#xD;
        PEEs can accumulate in the fatty tissue of the human body thanks to their lipophilic nature,&#xD;
        and are known as persistent organic pollutants (POPs).&#xD;
  &#xD;
        To assess the benefit of cholestyramine treatment on POPs blood levels in obese patients of&#xD;
        childbearing age undergoing bariatric surgery, in order to reduce their preoperative POPs&#xD;
        load more rapidly. Indeed, the investigators hypothesize that cholestyramine is capable,&#xD;
        outside of acute exposure accidents, of promoting the elimination and release of POPs in the&#xD;
        human population. Given this hypothesis, a treatment administered prior to bariatric surgery&#xD;
        could reduce pre-operative plasma levels of POPs and thus, in fine, minimize the&#xD;
        concentrations reached post-operatively, which are dependent on the release induced by&#xD;
        lipolysis (massive and rapid weight loss) and pre-operative plasma concentrations.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Environmental endocrine disruptors (EDCs) represent a major problem for human health. These&#xD;
        chemical compounds from industry (pesticides, paints, plastics, etc.) are present in our&#xD;
        daily lives, with exposure as early as foetal life. PEEs are capable of interfering with the&#xD;
        endocrine system, but also of disrupting the signalling pathways of carbohydrate and lipid&#xD;
        metabolism, and consequently of causing adverse effects on the health of an individual and/or&#xD;
        his or her offspring. They are implicated in numerous pathologies, notably those linked to&#xD;
        nervous system development, reproduction and chronic diseases such as obesity and diabetes.&#xD;
        Thanks to their lipophilic nature, some PEEs can accumulate in the adipose tissue of the&#xD;
        human body, and are known as persistent organic pollutants (POPs). Numerous longitudinal&#xD;
        epidemiological studies have demonstrated higher concentrations of PEEs, particularly POPs,&#xD;
        in obese and/or type 2 diabetic patients. In addition, these POPs pass easily across the&#xD;
        placenta into fetal blood and, more readily, into breast milk. The developing fetus and&#xD;
        infant are particularly sensitive to POPs, due to their lower volume of distribution and&#xD;
        immature metabolism pathways.&#xD;
  &#xD;
        In a recently published longitudinal study (PHRC POLOB), the investigators showed that&#xD;
        massive weight loss during the first year after bariatric surgery is associated with a&#xD;
        prolonged release of POPs from adipose tissue, directly dependent on pre-operative plasma&#xD;
        levels. For some compounds, this release exceeds the health reference values set by ANSES,&#xD;
        even one year after surgery. Short- and long-term consequences must therefore be considered,&#xD;
        particularly for obese women of childbearing age (60% of the population undergoing bariatric&#xD;
        surgery), because of the risks to the health of the unborn child in the event of pregnancy&#xD;
        occurring early after surgery, even if a 6-month delay is recommended between surgery and the&#xD;
        planning of a pregnancy.&#xD;
  &#xD;
        While health education is an important lever for limiting daily exposure, identifying a&#xD;
        treatment that can reduce the degree of exposure to EEPs is crucial, especially in a&#xD;
        population where pregnancy is planned in the short term. Cholestyramine is a bile salt&#xD;
        chelating resin used as a lipid-lowering treatment. It has been used off-label in a case of&#xD;
        accidental acute contamination by certain POPs, reducing plasma levels without adverse&#xD;
        effects, by promoting elimination through interaction with the enterohepatic cycle.&#xD;
  &#xD;
        The investigators hypothesize that cholestyramine is capable, outside of acute exposure&#xD;
        events, of promoting the elimination and release of POPs in the human population. Given this&#xD;
        hypothesis, a treatment administered prior to bariatric surgery could reduce pre-operative&#xD;
        plasma levels of POPs and thus, ultimately, minimize the concentrations reached&#xD;
        post-operatively, which are dependent on lipolysis-induced release (massive and rapid weight&#xD;
        loss) and pre-operative plasma concentrations. To confirm this hypothesis, the investigators&#xD;
        propose to evaluate in an exploratory way, on a selected cohort of patients, the effect of&#xD;
        pre-operative cholestyramine treatment on serum concentrations of different POPs before and&#xD;
        after bariatric surgery.&#xD;
  &#xD;
        If the results of this proof-of-concept study are positive, it will be possible to pursue the&#xD;
        study of cholestyramine with more powerful and comparative studies, with a view to eventually&#xD;
        considering a treatment to reduce the potentially harmful risks of POPs in cases of confirmed&#xD;
        pregnancy.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 31, 2023</start_date>
    <completion_date type="Anticipated">May 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">May 30, 2025</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Measurement of serum persistent organic pollutants (POPs) concentrations by mass spectrometry.</measure>
      <time_frame>19 month</time_frame>
      <description>Evaluation of the effect of cholestyramine treatment on serum concentrations of various persistent organic pollutants (POPs) in a population of population of obese women of childbearing age for whom bariatric surgery is bariatric surgery is indicated.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Measurement of serum POPs concentrations by mass spectrometry after bariatric surgery</measure>
      <time_frame>19 month</time_frame>
      <description>Evaluation of the effect of pre-operative cholestyramine treatment with respect to observed and expected post-bariatric surgery salting-out.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Obesity, Abdominal</condition>
    <condition>Diabetes</condition>
    <condition>Bariatric Surgery Candidate</condition>
    <arm_group>
      <arm_group_label>Cholestyramine intake</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>1 sachet (4 grams) 3 times a day, corresponding to a daily dose of 12 grams. Preferably taken at mealtimes.&#xD;
  Treatment lasts 4 months.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cholestyramine Powder</intervention_name>
      <description>Bile salt chelating resin, used as a lipid-lowering treatment.</description>
      <arm_group_label>Cholestyramine intake</arm_group_label>
      <other_name>Questran</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Female patients with a retained indication for bariatric surgery (BMI &gt; 40 kg/m2 or&#xD;
               BMI &gt; 35 kg/m2 with complication(s) amenable to improvement by surgery)&#xD;
  &#xD;
            -  Aged between 18 and 45&#xD;
  &#xD;
            -  Using effective contraception (oral contraception, hormonal or non-hormonal&#xD;
               intrauterine device, progestin implant), which will be adapted in the perioperative&#xD;
               period in accordance with current recommendations (HAS, BARIA-MAT)&#xD;
  &#xD;
            -  Affiliated to a social security scheme&#xD;
  &#xD;
            -  Have signed an informed consent form&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnant (urine pregnancy test) or breast-feeding women&#xD;
  &#xD;
            -  Known allergy or intolerance to cholestyramine&#xD;
  &#xD;
            -  Chronic constipation&#xD;
  &#xD;
            -  Chronic pathology likely to interfere with treatment efficacy (unbalanced diabetes&#xD;
               characterized by HbA1c &gt; 7%, known and treated dyslipidemia, chronic renal&#xD;
               insufficiency with GFR &lt; 60 ml/min, hepatocellular insufficiency)&#xD;
  &#xD;
            -  Patients receiving anti-vitamin K, digoxin or levothyroxine therapy, or likely to&#xD;
               receive such therapy within 3 months of inclusion.&#xD;
  &#xD;
            -  Phenylketonuria&#xD;
  &#xD;
            -  Inability to give consent&#xD;
  &#xD;
            -  Patient under legal protection (guardianship, curatorship, safeguard of justice...)&#xD;
  &#xD;
            -  Patient deprived of liberty by judicial or administrative decision,&#xD;
  &#xD;
            -  Patients under psychiatric care which makes it impossible for them to consent to&#xD;
               participation, or who are hospitalized under duress.&#xD;
  &#xD;
            -  Participation in another interventional study (outside the PaCO project).&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Nicolas CHEVALIER</last_name>
      <role>Principal Investigator</role>
      <affiliation>CHU Nice</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Nicolas CHEVALIER</last_name>
      <phone>04 92 03 55 19</phone>
      <email>chevalier.n@chu-nice.fr</email>
    </overall_contact>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 5, 2023</study_first_submitted>
    <study_first_submitted_qc>July 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 28, 2023</last_update_submitted>
    <last_update_submitted_qc>July 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>endocrine disrupter</keyword>
    <keyword>Obesity</keyword>
    <keyword>Diabetes</keyword>
    <keyword>Bariatric Surgery</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Obesity</mesh_term>
      <mesh_term>Obesity, Abdominal</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cholestyramine Resin</mesh_term>
    </intervention_browse>
    <!-- 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/NCT05966727
  org study id: 21-AOI-07
  nct id: NCT05966727
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Environmental endocrine disruptors (EDCs) represent a major problem for human health.Some
        PEEs can accumulate in the fatty tissue of the human body thanks to their lipophilic nature,
        and are known as persistent organic pollutants (POPs).
  
        To assess the benefit of cholestyramine treatment on POPs blood levels in obese patients of
        childbearing age undergoing bariatric surgery, in order to reduce their preoperative POPs
        load more rapidly. Indeed, the investigators hypothesize that cholestyramine is capable,
        outside of acute exposure accidents, of promoting the elimination and release of POPs in the
        human population. Given this hypothesis, a treatment administered prior to bariatric surgery
        could reduce pre-operative plasma levels of POPs and thus, in fine, minimize the
        concentrations reached post-operatively, which are dependent on the release induced by
        lipolysis (massive and rapid weight loss) and pre-operative plasma concentrations.
  Environmental endocrine disruptors (EDCs) represent a major problem for human health. These
        chemical compounds from industry (pesticides, paints, plastics, etc.) are present in our
        daily lives, with exposure as early as foetal life. PEEs are capable of interfering with the
        endocrine system, but also of disrupting the signalling pathways of carbohydrate and lipid
        metabolism, and consequently of causing adverse effects on the health of an individual and/or
        his or her offspring. They are implicated in numerous pathologies, notably those linked to
        nervous system development, reproduction and chronic diseases such as obesity and diabetes.
        Thanks to their lipophilic nature, some PEEs can accumulate in the adipose tissue of the
        human body, and are known as persistent organic pollutants (POPs). Numerous longitudinal
        epidemiological studies have demonstrated higher concentrations of PEEs, particularly POPs,
        in obese and/or type 2 diabetic patients. In addition, these POPs pass easily across the
        placenta into fetal blood and, more readily, into breast milk. The developing fetus and
        infant are particularly sensitive to POPs, due to their lower volume of distribution and
        immature metabolism pathways.
  
        In a recently published longitudinal study (PHRC POLOB), the investigators showed that
        massive weight loss during the first year after bariatric surgery is associated with a
        prolonged release of POPs from adipose tissue, directly dependent on pre-operative plasma
        levels. For some compounds, this release exceeds the health reference values set by ANSES,
        even one year after surgery. Short- and long-term consequences must therefore be considered,
        particularly for obese women of childbearing age (60% of the population undergoing bariatric
        surgery), because of the risks to the health of the unborn child in the event of pregnancy
        occurring early after surgery, even if a 6-month delay is recommended between surgery and the
        planning of a pregnancy.
  
        While health education is an important lever for limiting daily exposure, identifying a
        treatment that can reduce the degree of exposure to EEPs is crucial, especially in a
        population where pregnancy is planned in the short term. Cholestyramine is a bile salt
        chelating resin used as a lipid-lowering treatment. It has been used off-label in a case of
        accidental acute contamination by certain POPs, reducing plasma levels without adverse
        effects, by promoting elimination through interaction with the enterohepatic cycle.
  
        The investigators hypothesize that cholestyramine is capable, outside of acute exposure
        events, of promoting the elimination and release of POPs in the human population. Given this
        hypothesis, a treatment administered prior to bariatric surgery could reduce pre-operative
        plasma levels of POPs and thus, ultimately, minimize the concentrations reached
        post-operatively, which are dependent on lipolysis-induced release (massive and rapid weight
        loss) and pre-operative plasma concentrations. To confirm this hypothesis, the investigators
        propose to evaluate in an exploratory way, on a selected cohort of patients, the effect of
        pre-operative cholestyramine treatment on serum concentrations of different POPs before and
        after bariatric surgery.
  
        If the results of this proof-of-concept study are positive, it will be possible to pursue the
        study of cholestyramine with more powerful and comparative studies, with a view to eventually
        considering a treatment to reduce the potentially harmful risks of POPs in cases of confirmed
        pregnancy.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Measurement of serum persistent organic pollutants (POPs) concentrations by mass spectrometry.
  time frame: 19 month
  description: Evaluation of the effect of cholestyramine treatment on serum concentrations of various persistent organic pollutants (POPs) in a population of population of obese women of childbearing age for whom bariatric surgery is bariatric surgery is indicated.
  measure: Measurement of serum POPs concentrations by mass spectrometry after bariatric surgery
  time frame: 19 month
  description: Evaluation of the effect of pre-operative cholestyramine treatment with respect to observed and expected post-bariatric surgery salting-out.
  arm group label: Cholestyramine intake
  arm group type: Experimental
  description: 1 sachet (4 grams) 3 times a day, corresponding to a daily dose of 12 grams. Preferably taken at mealtimes.
  Treatment lasts 4 months.
  intervention type: Drug
  intervention name: Cholestyramine Powder
  description: Bile salt chelating resin, used as a lipid-lowering treatment.
  arm group label: Cholestyramine intake
  other name: Questran
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 45 Years
  healthy volunteers: No
  last name: Nicolas CHEVALIER
  role: Principal Investigator
  affiliation: CHU Nice
  last name: Nicolas CHEVALIER
  phone: 04 92 03 55 19
  email: chevalier.n@chu-nice.fr
  responsible party type: Sponsor
  mesh term: Obesity
  mesh term: Obesity, Abdominal
  mesh term: Cholestyramine Resin