Biomarkers for Intestinal Permeability in Patients With Constipation

August 19, 2019 updated by: Madhusudan (Madhu) Grover, MBBS, Mayo Clinic

Biomarkers for Intestinal Permeability in Patients With Functional Lower Gastrointestinal Disorders Associated With Constipation.

Our overall objective with this study is firstly to provide a comprehensive assessment of intestinal permeability, mucosal barrier function using existing biomarkers and secondly to explore novel biomarkers for measuring intestinal permeability in patients with constipation predominant Irritable Bowel Syndrome (IBS-C).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In order to determine the differences in permeability in IBS-C in comparison with healthy volunteers, the following will be determined: differences in in vivo small intestinal and colonic permeability, differences in small intestinal and colonic mucosal barrier function, differences in effects of fecal supernatants on barrier function of T84 monolayers, and differences in novel biomarkers for intestinal permeability

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
39

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

IBS-Constipation patients and healthy volunteers

Description

Inclusion criteria:

  1. 18 - 65 years old
  2. IBS-C by Rome III criteria (for IBS-C participants)
  3. No abdominal surgery (except appendectomy and cholecystectomy)

Exclusion criteria:

  1. History of Inflammatory Bowel Disease (IBD) , microscopic colitis or celiac disease
  2. Use of tobacco products within the past 6 months
  3. Use of NSAIDs or aspirin within the past week
  4. Use of oral corticosteroids within the previous 6 weeks
  5. Ingestion of artificial sweeteners such as Splenda (sucralose), Nutrasweet (aspartame), lactulose or mannitol 2 days before the study begins, e.g., foods to be avoided are sugarless gums or mints and diet soda

  6. Ingestion of any prescription, over the counter, or herbal medications which can affect gastrointestinal transit 7 days before study begins

    1. Any treatment specifically taken for IBS, including loperamide, cholestyramine, alosetron
    2. Drugs with a known pharmacological activity at 5-HT4, 5-HT2b or 5-HT3 receptors (e.g, tegaserod, ondansetron, tropisetron, granisetron, dolasetron, mirtazapine);
    3. All narcotics (e.g, codeine, morphine, and propoxyphene, either alone or in combination)
    4. Anti-cholinergic agents (e.g, dicyclomine, hyoscyamine, propantheline).
    5. Ultram

    6. GI preparations

      • Anti-nausea agents (e.g, trimethobenzamide, promethazine, prochlorperazine, dimenhydrinate, hydroxyzine)
      • Osmotic laxative agents (e.g, lactulose, sorbitol or PEG solutions as Miralax and Glycolax)
      • Prokinetic agents (e.g, cisapride, metoclopramide, itopride, domperidone);
    7. Antimuscarinics;
    8. Peppermint oil;
    9. Systemic antibiotics, rifaximin, metronidazole.
  7. Bleeding disorders or medications that increase risk of bleeding from mucosal biopsies.
  8. Score > 8 for anxiety or depression on Hospital anxiety and depression scale.
  9. Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Healthy volunteers
Permeability measurement: Ingestion of saccharides {mannitol (regular, 12C) 100 mg, lactulose 1 g and labelled (13C mannitol) 100 mg} in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy
Diagnostic test: Permeability measurement
Saccharide excretion was compared between IBS-C and healthy volunteers
Other Names:
  • Lactulose
  • 12C Mannitol
  • 13C Mannitol
Procedure: Esophagogastroduodenoscopy
Duodenal biopsies were collected from IBS-C and healthy volunteers
Procedure: Flexible sigmoidoscopy
Colonic biopsies were collected from IBS-C and healthy volunteers
IBS-C
Permeability measurement: Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and labelled (13C mannitol) 100 mg} in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy
Diagnostic test: Permeability measurement
Saccharide excretion was compared between IBS-C and healthy volunteers
Other Names:
  • Lactulose
  • 12C Mannitol
  • 13C Mannitol
Procedure: Esophagogastroduodenoscopy
Duodenal biopsies were collected from IBS-C and healthy volunteers
Procedure: Flexible sigmoidoscopy
Colonic biopsies were collected from IBS-C and healthy volunteers

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Lactulose:C13 Mannitol Excretion Ratio 8-24hrs.
Time Frame: 8-24 hr post test-dose administration
In vivo measurement of intestinal permeability using 13C mannitol & lactulose was used. High performance liquid chromatography-tandem mass spectrometry was used to measure concentrations calculated using the overall urine volume excreted in each interval. Concentrations of 13C adjusted for the % of 13C in 12C mannitol (4.98% of 12C mannitol excreted was subtracted from 13C mannitol values; determined by analyzing replicate samples of control urine). All lactulose or 13C mannitol concentrations 8-24hr post-ingestion were used to determine colonic permeability. Lactulose to 13C mannitol excretion ratios, as a measure of dose of saccharide administered, were calculated.
8-24 hr post test-dose administration

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Lactose:C13 Mannitol Excretion Ratio 0-2hours
Time Frame: 0-2 hr post-test dose administration
0-2 hr post-test dose administration
Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa
Time Frame: Baseline
Baseline
Cumulative FITC-Dextran (4kDa) Concentration Across Duodenal Mucosa
Time Frame: 3 hours post FITC-Dextran (4kDa) administration
This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.
3 hours post FITC-Dextran (4kDa) administration
Rate of FITC-Dextran (4kDa) Flux Across Duodenal Mucosa
Time Frame: Over 3 hours post FITC-Dextran (4kDa) administration
This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.
Over 3 hours post FITC-Dextran (4kDa) administration
Baseline Transmucosal Resistance (TMR) of Colonic Mucosa
Time Frame: Baseline
Baseline
Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa
Time Frame: 3 hours post FITC-Dextran (4kDa) administration
3 hours post FITC-Dextran (4kDa) administration
Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa
Time Frame: Over 3 hours post FITC-Dextran (4kDa) administration
Over 3 hours post FITC-Dextran (4kDa) administration
Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa
Time Frame: 3 hours post E.coli Bio- Particle administration
3 hours post E.coli Bio- Particle administration
Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa
Time Frame: Over 3 hours post E.coli Bio- Particle administration
Over 3 hours post E.coli Bio- Particle administration
Cumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa
Time Frame: 3 hours post E.coli Bio- Particle administration
3 hours post E.coli Bio- Particle administration
Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa
Time Frame: Over 3 hours post E.coli Bio- Particle administration
Over 3 hours post E.coli Bio- Particle administration
Duodenal Impedance
Time Frame: Baseline
Baseline
Mean Serum Endotoxin (Bacterial LPS) Levels
Time Frame: Fasting, one time measurement after 8 hours
Fasting, one time measurement after 8 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mayo Clinic

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Takeda Pharmaceuticals International, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 8, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 8, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 18, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 18, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 23, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 21, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 19, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 14-002382

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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