Intestinal DiseasesNCT02246647
Biomarkers for Intestinal Permeability in Patients With Constipation
An observational study of Intestinal Diseases and Irritable Bowel Syndrome, run by Mayo Clinic at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 65 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Intestinal Diseases, Irritable Bowel Syndrome, Constipation
- What is being tested?
- Permeability measurement, Esophagogastroduodenoscopy and Flexible sigmoidoscopy
- Type of treatment
- Surgery or procedure
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to 8 Dec 2016
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: IBS-Constipation patients and healthy volunteers
Who may be able to join
- 18 - 65 years old
- IBS-C by Rome III criteria (for IBS-C participants)
- No abdominal surgery (except appendectomy and cholecystectomy)
Who cannot join
- History of Inflammatory Bowel Disease (IBD) , microscopic colitis or celiac disease
- Use of tobacco products within the past 6 months
- Use of NSAIDs or aspirin within the past week
- Use of oral corticosteroids within the previous 6 weeks
- 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
- Ingestion of any prescription, over the counter, or herbal medications which can affect gastrointestinal transit 7 days before study begins
Show all 21Show fewer
- Any treatment specifically taken for IBS, including loperamide, cholestyramine, alosetron
- Drugs with a known pharmacological activity at 5-HT4, 5-HT2b or 5-HT3 receptors (e.g, tegaserod, ondansetron, tropisetron, granisetron, dolasetron, mirtazapine);
- All narcotics (e.g, codeine, morphine, and propoxyphene, either alone or in combination)
- Anti-cholinergic agents (e.g, dicyclomine, hyoscyamine, propantheline).
- Ultram
- 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);
- Antimuscarinics;
- Peppermint oil;
- Systemic antibiotics, rifaximin, metronidazole.
- Bleeding disorders or medications that increase risk of bleeding from mucosal biopsies.
- Score > 8 for anxiety or depression on Hospital anxiety and depression scale.
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: 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).
Read the 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
- Conditions
- Intestinal Diseases, Irritable Bowel Syndrome, Constipation
- Being tested
- Permeability measurement, Esophagogastroduodenoscopy, Flexible sigmoidoscopy
- Medical subject headings
- Intestinal Diseases, Irritable Bowel Syndrome, Constipation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Permeability measurementDiagnostic test
Also called 12C Mannitol, 13C Mannitol, Lactulose
Saccharide excretion was compared between IBS-C and healthy volunteers
EsophagogastroduodenoscopyProcedure or surgery
Duodenal biopsies were collected from IBS-C and healthy volunteers
Flexible sigmoidoscopyProcedure or surgery
Colonic biopsies were collected from IBS-C and healthy volunteers
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Diagnostic Test: Permeability measurement; Procedure: Esophagogastroduodenoscopy; Procedure: Flexible sigmoidoscopy | |
| 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 Receives: Diagnostic Test: Permeability measurement; Procedure: Esophagogastroduodenoscopy; Procedure: Flexible sigmoidoscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lactulose:C13 Mannitol Excretion Ratio 8-24hrs.
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.
Measured: 8-24 hr post test-dose administration
Secondary outcomes (13)
Lactose:C13 Mannitol Excretion Ratio 0-2hours
Measured: 0-2 hr post-test dose administration
Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa
Measured: Baseline
Cumulative FITC-Dextran (4kDa) Concentration Across Duodenal Mucosa
This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.
Measured: 3 hours post FITC-Dextran (4kDa) administration
Rate of FITC-Dextran (4kDa) Flux Across Duodenal Mucosa
This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.
Measured: Over 3 hours post FITC-Dextran (4kDa) administration
Baseline Transmucosal Resistance (TMR) of Colonic Mucosa
Measured: Baseline
Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa
Measured: 3 hours post FITC-Dextran (4kDa) administration
Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa
Measured: Over 3 hours post FITC-Dextran (4kDa) administration
Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa
Measured: 3 hours post E.coli Bio- Particle administration
Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa
Measured: Over 3 hours post E.coli Bio- Particle administration
Cumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa
Measured: 3 hours post E.coli Bio- Particle administration
Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa
Measured: Over 3 hours post E.coli Bio- Particle administration
Duodenal Impedance
Measured: Baseline
Mean Serum Endotoxin (Bacterial LPS) Levels
Measured: Fasting, one time measurement after 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2014 (estimated)
- Study startSep 2014
- Primary completion8 Dec 2016
- Study completion8 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Intestinal DiseasesStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda Pharmaceuticals International, Inc.
- Responsible party
- Principal investigator, Madhusudan (Madhu) Grover, MBBS, Mayo Clinic
- Investigators
- Madhusudan Grover, MBBS, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02246647
- Sponsor's protocol ID
- 14-002382
- Status last verified
- Aug 2019
- First submitted
- 18 Sep 2014
- Last updated
- 21 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers for Intestinal Permeability in Patients With Functional Lower Gastrointestinal Disorders Associated With Constipation.
- ClinicalTrials.gov ID
- NCT02246647
- Acronym / sponsor ID
- 14-002382
- Conditions
- Intestinal Diseases, Irritable Bowel Syndrome, Constipation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Takeda Pharmaceuticals International, Inc.
- Study start
- Sep 2014
- Primary completion
- 8 Dec 2016 (actual)
- Study completion
- 8 Dec 2016 (actual)
- First posted
- 23 Sep 2014 (estimated)
- Results
- Posted 21 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy volunteers | – | Diagnostic Test: Permeability measurement, Procedure: Esophagogastroduodenoscopy, Procedure: Flexible sigmoidoscopyPermeability 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 |
| IBS-C | – | Diagnostic Test: Permeability measurement, Procedure: Esophagogastroduodenoscopy, Procedure: Flexible sigmoidoscopyPermeability 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- IBS-Constipation patients and healthy volunteers
Key inclusion criteria (3 listed)
- 18 - 65 years old
- IBS-C by Rome III criteria (for IBS-C participants)
- No abdominal surgery (except appendectomy and cholecystectomy)
Key exclusion criteria (21 listed)
- History of Inflammatory Bowel Disease (IBD) , microscopic colitis or celiac disease
- Use of tobacco products within the past 6 months
- Use of NSAIDs or aspirin within the past week
- Use of oral corticosteroids within the previous 6 weeks
- 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
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 |
|---|---|---|
| Permeability measurementAlso: 12C Mannitol, 13C Mannitol, LactuloseSaccharide excretion was compared between IBS-C and healthy volunteers | Diagnostic test | Healthy volunteers, IBS-C |
| EsophagogastroduodenoscopyDuodenal biopsies were collected from IBS-C and healthy volunteers | Procedure or surgery | Healthy volunteers, IBS-C |
| Flexible sigmoidoscopyColonic biopsies were collected from IBS-C and healthy volunteers | Procedure or surgery | Healthy volunteers, IBS-C |
Primary outcome
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.
13 secondary outcomes
Lactose:C13 Mannitol Excretion Ratio 0-2hours
Time frame: 0-2 hr post-test dose administration
Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa
Time frame: Baseline
Cumulative FITC-Dextran (4kDa) Concentration Across Duodenal Mucosa
Time frame: 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
Baseline Transmucosal Resistance (TMR) of Colonic Mucosa
Time frame: Baseline
Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa
Time frame: 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
Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa
Time frame: 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
Cumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa
Time frame: 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
Duodenal Impedance
Time frame: Baseline
Mean Serum Endotoxin (Bacterial LPS) Levels
Time frame: Fasting, one time measurement after 8 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Madhusudan Grover, MBBS principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Intestinal Diseases and Irritable Bowel Syndrome, run by Mayo Clinic at 1 site in United States.
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 3 inclusion and 21 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: finished, as of the sponsor's last update on 21 Aug 2019. 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 United States. 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?
Yes. Results are posted in the registry (first posted 21 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Lactulose:C13 Mannitol Excretion Ratio 8-24hrs. (time frame: 8-24 hr post test-dose administration). 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 21 Aug 2019.