Intestinal Permeability in Obesity

Not Applicable

Terminated

• Conditions: Metabolic Diseases; Obesity; Nutrition Disorders; Body Weight
• Interventions: Procedure: Intestinal permeability; Other: a solution of mannitol and lactitol

• Registration Number: NCT02292121
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

In rodents, obesity is associated with changes in tight junctions' structure in small intestine, which impacts intestinal permeability and results in metabolic complications. Few data exist in human. We hypothesized that intestinal permeability is altered in obese subjects in comparison to lean subjects, linked to metabolic and inflammatory status and that these alterations are modified after gastric bypass.

Detailed Description

The regulation of the permeability of the intestinal barrier is essential in the molecular traffic between the lumen and the internal environment. It affects the absorption of nutrients and tolerance or immunization against foodborne non-self antigens that penetrate the barrier. In rodents, increased endotoxemia has been proposed as an important player in low-grade inflammation accompanying the development of obesity and metabolic disorders. In humans, the intestinal barrier function is altered in inflammatory bowel diseases (IBD, Crohn's disease, ulcerative colitis and celiac disease). The term "leaky gut" is used to describe a porous intestine with hyper-permeability associated with acute or chronic inflammatory diseases such as "systemic inflammatory response syndrome (SIRS),"acute inflammatory bowel disease (IBD for "inflammatory bowel disease").

Deficiencies of the barrier are also observed in extra-intestinal diseases (type-1 diabetes, food allergies, and autoimmune diseases). Impairments in tight junctions may precede clinical signs and constitute a risk factor for developing diseases or secondarily be altered and cause an increased entry of undesirable bacterial or nutritional antigens. The state of the intercellular tight junctions of the intestine controls the diffusion of molecules between cells. A deficiency of the intestinal barrier function is often associated with structural changes in the tight junctions resulting from loss of localization of protein or expression of genes and / or cellular signals such as ZO-1, occludin or tricellulin.

There are few studies about the condition of the intestinal barrier in the context of human obesity.

The objectives of our study are to :

* compare intestinal permeability in obese subjects with non obese subjects and after gastric bypass.

* search links between intestinal permeability and 1) metabolic and inflammatory bioclinical parameters 2) dietary profiles 3) microbiota

Study Timeline

• Study Start: 2014-02-24
• Study First Submitted: 2014-11-12
• Study First Submitted QC: 2014-11-14
• Study First Posted: 2014-11-17
• Primary Completion: 2016-03-17
• Study Completion: 2016-03-17
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-15
• Last Update Posted: 2021-01-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
non-obese control group (T1)	Intestinal permeability	30 non-obese control subjects investigated for bio-clinical measures, IPT, zonulin, and LPS
obese group	a solution of mannitol and lactitol	40 obese subjects undergoing gastric bypass explored at baseline and 30 explored post-surgery at 6 months
non-obese control group (T1)	a solution of mannitol and lactitol	30 non-obese control subjects investigated for bio-clinical measures, IPT, zonulin, and LPS
obese group	Intestinal permeability	40 obese subjects undergoing gastric bypass explored at baseline and 30 explored post-surgery at 6 months

Primary Outcome Measures

Name	Time	Method
urinary lactitol / mannitol ratio by an intestinal permeability test (IPT)	before gastric bypass and 6 months after	Measures of urinary lactitol / mannitol ratio by an intestinal permeability test (IPT) in obese patients before gastric bypass and 6 months after

Secondary Outcome Measures

Name	Time	Method
surgical samples during surgery (sub-cutaneous and visceral adipose tissue)	intraoperative
fasting zonulin serum concentrations	before gastric bypass and 6 months after	Measures of fasting zonulin serum concentrations in obese patients before gastric bypass and 6 months after
urinary lactitol / mannitol ratio by an intestinal permeability test (IPT)	inclusion and after one month	Measures of urinary lactitol / mannitol ratio by an intestinal permeability test (IPT) in non-obese control subjects, performed twice with a one-month interval.
LPS serum concentrations	before gastric bypass and 6 months after	Measures of LPS serum concentrations in obese patients before gastric bypass and 6 months after

Trial Locations

Locations (1)

Groupe Hospitalier Pitié-Salpêtrière; 🇫🇷 Paris, France