ObesityLEAKY GUTNCT02292121
Intestinal Permeability in Obesity
A study testing Intestinal permeability and a solution of mannitol and lactitol in people with Obesity and Metabolic Diseases, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Obesity, Metabolic Diseases, Nutrition Disorders
- What is being tested?
- Intestinal permeability and a solution of mannitol and lactitol
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteFrance
- Study dates
- 24 Feb 2014to 17 Mar 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Control subjects T1:
- Registered for social security
- Signed consent form
- male or female subject between 18 and 65 years old
- Fasting plasma triglycerides < 1.5 g/l (< 1.7 mmol/l)
- Fasting plasma total cholesterol < 2.5 g/l (< 6 mmol/l)
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- fasting glycaemia < 5,5 mmol/l
- BMI <25kg/m² \& >18 kg/m²
- Mean systolic blood pressure <140 mmHg and mean diastolic blood pressure < 90 mmHg.
- Control subjects T2
- Registered for social security
- Signed consent form
- male or female subject between 18 and 70 years old
- IMC<25kg/m² et >18 kg/m²
- candidate to surgery giving access to jejunal samples
- Obese subjects OB:
- Registered for social security
- Signed consent form
- male or female subject between 18 and 65 years old
- Candidate to bariatric surgery (bypass) with massive (IBMI >= 40 kg/m²) or severe obesity (BMI between 35 \& 40 kg/m²) with at least one obesity-related comorbidity and with a stable weight (+/-5kg) for the last 3 months, after approval by a multidisciplinary team
Who cannot join
- Control subjects T1:
- Subject with a history of vascular symptomatic disease in the last 6 months before selection.
- Subject receiving a treatment that can affect measured parameters
- Pregnancy
- Subject with acute or chronic disease that can affect measured parameters or to life-threatening. Including but not limited :
- Diabetic subjects
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- Subject with kidney disease: nephrotic syndrome, chronic renal failure
- Subject having a gastrointestinal disorder or disease limiting intestinal absorption (celiac disease), bariatric surgery.
- Active inflammatory disease or a history of IBD
- Subject in a situation that, according to the investigator's opinion could interfere with an optimal participation to the study or constitute a particular risk to the subject
- Subject in an exclusion period after participating in another clinical trial
- Adult person subject to legal protection or unable to consent.
- Persons deprived of their liberty by judicial or administrative decision
- Control subjects T2
- Subject with a history of symptomatic vascular disease (myocardial infarction, angina syndrome threat, surgical or endovascular surgery, stroke, lower limb arteritis symptomatic) of less than 6 months
- Subject with any acute or chronic disease which may influence the results of the study or to life-threatening. Including but not limiting:
- diabetic patients
- Subject with kidney disease: nephrotic syndrome, chronic renal failure and / or serum creatinine> 1.7 times the upper limit of the reference value
- Adult person subject to legal protection or unable to consent.
- Persons deprived of their liberty by judicial or administrative decision
- Obese subjects candidates for surgery:
- Subject receiving treatment systemically or topically, which may interfere with the evaluation of the parameters studied (NSAIDs, antibiotics in the previous month)
- Any disease or psychosocial context making prolonged regular monitoring impossible, which also represents a contraindication for bariatric surgery.
- Adult person subject to legal protection or unable to consent.
- Persons deprived of their liberty by judicial or administrative decision
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Intestinal Permeability in Obesity of Intercellular Tight Junctions to Metabolic Complications
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.
Read the 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
- Conditions
- Obesity, Metabolic Diseases, Nutrition Disorders, Body Weight
- Being tested
- Intestinal permeability, a solution of mannitol and lactitol
- Keywords
- Obesity, Intestinal permeability, Adipose tissue inflammation, Low grade systemic inflammation, Bariatric surgery
- Medical subject headings
- Obesity, Metabolic Diseases, Nutrition Disorders, Body Weight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intestinal permeabilityProcedure or surgery
5h-intestinal permeability test 10-hour overnight fasting subject who first emptied his bladder drinks a solution of mannitol and lactitol. 2 hours after, the subject drinks 500mL of water in less than 30 minutes. All urine samples are collected during the 5h-test for measurement of lactitol and mannitol.
a solution of mannitol and lactitolOther
| Study group | Role | What they receive |
|---|---|---|
| obese group | Experimental | 40 obese subjects undergoing gastric bypass explored at baseline and 30 explored post-surgery at 6 months Receives: Procedure: Intestinal permeability; Other: a solution of mannitol and lactitol |
| non-obese control group (T1) | Active comparator | 30 non-obese control subjects investigated for bio-clinical measures, IPT, zonulin, and LPS Receives: Procedure: Intestinal permeability; Other: a solution of mannitol and lactitol |
| non obese control group undergoing a surgery (T2) | No intervention | 40 non-obese candidates to a surgery that gives access to surgical jejunal samples to measure the expression of tight junctions proteins |
What is being measured
The primary outcome is the main question the study is designed to answer.
urinary lactitol / mannitol ratio by an intestinal permeability test (IPT)
Measures of urinary lactitol / mannitol ratio by an intestinal permeability test (IPT) in obese patients before gastric bypass and 6 months after
Measured: before gastric bypass and 6 months after
Secondary outcomes (4)
fasting zonulin serum concentrations
Measures of fasting zonulin serum concentrations in obese patients before gastric bypass and 6 months after
Measured: before gastric bypass and 6 months after
LPS serum concentrations
Measures of LPS serum concentrations in obese patients before gastric bypass and 6 months after
Measured: before gastric bypass and 6 months after
urinary lactitol / mannitol ratio by an intestinal permeability test (IPT)
Measures of urinary lactitol / mannitol ratio by an intestinal permeability test (IPT) in non-obese control subjects, performed twice with a one-month interval.
Measured: inclusion and after one month
surgical samples during surgery (sub-cutaneous and visceral adipose tissue)
Measured: intraoperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2014 (estimated)
- Study start24 Feb 2014
- Primary completion17 Mar 2016
- Study completion17 Mar 2016
Why it stopped: lack of surgical controls
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Institute of Cardiometabolism and Nutrition, France
- Responsible party
- Sponsor
- Investigators
- Christine POITOU, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02292121
- Sponsor's protocol ID
- P130402
- Acronym
- LEAKY GUT
- Status last verified
- Jan 2021
- First submitted
- 12 Nov 2014
- Last updated
- 20 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intestinal Permeability in Obesity of Intercellular Tight Junctions to Metabolic Complications
- ClinicalTrials.gov ID
- NCT02292121
- Acronym / sponsor ID
- LEAKY GUT / P130402
- Conditions
- Obesity, Metabolic Diseases, Nutrition Disorders, Body Weight
- Keywords
- Obesity, Intestinal permeability, Adipose tissue inflammation, Low grade systemic inflammation, Bariatric surgery
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of surgical controls
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Institute of Cardiometabolism and Nutrition, France
- Study start
- 24 Feb 2014 (actual)
- Primary completion
- 17 Mar 2016 (actual)
- Study completion
- 17 Mar 2016 (actual)
- First posted
- 17 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| obese group | Experimental | Procedure: Intestinal permeability, Other: a solution of mannitol and lactitol40 obese subjects undergoing gastric bypass explored at baseline and 30 explored post-surgery at 6 months |
| non-obese control group (T1) | Active comparator | Procedure: Intestinal permeability, Other: a solution of mannitol and lactitol30 non-obese control subjects investigated for bio-clinical measures, IPT, zonulin, and LPS |
| non obese control group undergoing a surgery (T2) | No intervention | –40 non-obese candidates to a surgery that gives access to surgical jejunal samples to measure the expression of tight junctions proteins |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Control subjects T1:
- Registered for social security
- Signed consent form
- male or female subject between 18 and 65 years old
- Fasting plasma triglycerides < 1.5 g/l (< 1.7 mmol/l)
Key exclusion criteria (25 listed)
- Control subjects T1:
- Subject with a history of vascular symptomatic disease in the last 6 months before selection.
- Subject receiving a treatment that can affect measured parameters
- Pregnancy
- Subject with acute or chronic disease that can affect measured parameters or to life-threatening. Including but not limited :
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intestinal permeability5h-intestinal permeability test 10-hour overnight fasting subject who first emptied his bladder drinks a solution of mannitol and lactitol. 2 hours after, the subject drinks 500mL of water in less than 30 minutes. All urine samples are collected during the 5h-test for measurement of lactitol and mannitol. | Procedure or surgery | non-obese control group (T1), obese group |
| a solution of mannitol and lactitol | Other | non-obese control group (T1), obese group |
Primary outcome
urinary lactitol / mannitol ratio by an intestinal permeability test (IPT)
Time frame: 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
4 secondary outcomes
fasting zonulin serum concentrations
Time frame: before gastric bypass and 6 months after
LPS serum concentrations
Time frame: before gastric bypass and 6 months after
urinary lactitol / mannitol ratio by an intestinal permeability test (IPT)
Time frame: inclusion and after one month
surgical samples during surgery (sub-cutaneous and visceral adipose tissue)
Time frame: intraoperative
Results and safety
The study was stopped early (reason given: lack of surgical controls). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christine POITOU, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intestinal permeability and a solution of mannitol and lactitol in people with Obesity and Metabolic Diseases, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: lack of surgical controls). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
urinary lactitol / mannitol ratio by an intestinal permeability test (IPT) (time frame: before gastric bypass and 6 months after). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2021.