Exploratory Evaluation of the Effect of Cholestyramine on Serum Levels of POPs in Obese Female Patients (OBESE)

Exploratory Evaluation of the Effect of Cholestyramine on Serum Levels of Persistent Organic Pollutants in Obese Female Patients - OBESE (OBesity, cholEStyramine, womEn)

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetes; Bariatric Surgery Candidate; Obesity, Abdominal
• Intervention / Treatment: Drug: Cholestyramine Powder

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nicolas CHEVALIER; Phone Number: 04 92 03 55 19; Email: chevalier.n@chu-nice.fr

Study Locations

• France
  • Alpes-Mritimes
    • Nice, Alpes-Mritimes, France, 06300
      • Recruiting
      • CHU Nice - Hôpital de l'Archet 2
      • Contact: Nicolas CHEVALIER; Phone Number: +33 04 92 03 55 19; Email: chevalier.n@chu-nice.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female patients with a retained indication for bariatric surgery (BMI > 40 kg/m2 or BMI > 35 kg/m2 with complication(s) amenable to improvement by surgery)
• Aged between 18 and 45
• Using effective contraception (oral contraception, hormonal or non-hormonal intrauterine device, progestin implant), which will be adapted in the perioperative period in accordance with current recommendations (HAS, BARIA-MAT)
• Affiliated to a social security scheme
• Have signed an informed consent form

Exclusion Criteria:

• Pregnant (urine pregnancy test) or breast-feeding women
• Known allergy or intolerance to cholestyramine
• Chronic constipation
• Chronic pathology likely to interfere with treatment efficacy (unbalanced diabetes characterized by HbA1c > 7%, known and treated dyslipidemia, chronic renal insufficiency with GFR < 60 ml/min, hepatocellular insufficiency)
• Patients receiving anti-vitamin K, digoxin or levothyroxine therapy, or likely to receive such therapy within 3 months of inclusion.
• Phenylketonuria
• Inability to give consent
• Patient under legal protection (guardianship, curatorship, safeguard of justice...)
• Patient deprived of liberty by judicial or administrative decision,
• Patients under psychiatric care which makes it impossible for them to consent to participation, or who are hospitalized under duress.
• Participation in another interventional study (outside the PaCO project).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cholestyramine intake; 1 sachet (4 grams) 3 times a day, corresponding to a daily dose of 12 grams. Preferably taken at mealtimes. Treatment lasts 4 months.	Drug: Cholestyramine Powder; Bile salt chelating resin, used as a lipid-lowering treatment.; Other Names: Questran

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of serum persistent organic pollutants (POPs) concentrations by mass spectrometry.	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.	19 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of serum POPs concentrations by mass spectrometry after bariatric surgery	Evaluation of the effect of pre-operative cholestyramine treatment with respect to observed and expected post-bariatric surgery salting-out.	19 month

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice
• Investigators: Principal Investigator: Nicolas CHEVALIER, CHU Nice

Study record dates

Study Major Dates

• Study Start (Estimated): March 31, 2024
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: July 5, 2023
• First Submitted That Met QC Criteria: July 28, 2023
• First Posted (Actual): August 1, 2023

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Diabetes; Obesity; Bariatric Surgery; endocrine disrupter
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Obesity, Abdominal; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Cholestyramine Resin
• Other Study ID Numbers: 21-AOI-07

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No