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CompletedNCT02246647Updated Aug 21, 2019Results posted

Biomarkers for Intestinal Permeability in Patients With Constipation

An observational study in Intestinal Diseases, Irritable Bowel Syndrome and Constipation, sponsored by Mayo Clinic. Completed at 1 site in United States. Open to female participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-08-21.

Sponsored by Mayo Clinic · Observational

Study type
Observational
Model
Case-control
Time perspective
Cross-sectional
Enrollment
39
Ages
18 Years to 65 Years
Sex
Female
01

Study 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 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

02

Conditions studied

  • Intestinal Diseases
  • Irritable Bowel Syndrome
  • Constipation
03

In context

Irritable Bowel Syndrome

1,062 studies on the registry are indexed under Irritable Bowel Syndrome; 190 are open to participants now.

This study's enrollment of 39 is below the median of 150 across 178 observational studies indexed under Irritable Bowel Syndrome.

Browse Irritable Bowel Syndrome studies →

Lead sponsor

Mayo Clinic is the lead sponsor of 3,218 studies on the registry; 670 are open to participants now.

Of its 445 completed or terminated interventional studies of FDA-regulated products, 313 (70%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes
Sampling method
Probability sample

Study population

IBS-Constipation patients and healthy volunteers

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

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
05

Study design

Observational model
Case-control
Time perspective
Cross-sectional
Enrollment
39 participants (actual)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • 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 · 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

    Diagnostic Test: Permeability measurement · Procedure: Esophagogastroduodenoscopy · Procedure: Flexible sigmoidoscopy

Interventions

  • Diagnostic testPermeability measurement

    Saccharide excretion was compared between IBS-C and healthy volunteers

    Also known as: 12C Mannitol, 13C Mannitol, Lactulose

  • ProcedureEsophagogastroduodenoscopy

    Duodenal biopsies were collected from IBS-C and healthy volunteers

  • ProcedureFlexible sigmoidoscopy

    Colonic biopsies were collected from IBS-C and healthy volunteers

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 8-24 hr post test-dose administration

Secondary outcomes

  1. Lactose:C13 Mannitol Excretion Ratio 0-2hours

    Time frame: 0-2 hr post-test dose administration

  2. Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa

    Time frame: Baseline

  3. 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.

    Time frame: 3 hours post FITC-Dextran (4kDa) administration

  4. 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.

    Time frame: Over 3 hours post FITC-Dextran (4kDa) administration

  5. Baseline Transmucosal Resistance (TMR) of Colonic Mucosa

    Time frame: Baseline

  6. Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa

    Time frame: 3 hours post FITC-Dextran (4kDa) administration

  7. Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa

    Time frame: Over 3 hours post FITC-Dextran (4kDa) administration

  8. Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa

    Time frame: 3 hours post E.coli Bio- Particle administration

  9. Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa

    Time frame: Over 3 hours post E.coli Bio- Particle administration

  10. Cumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa

    Time frame: 3 hours post E.coli Bio- Particle administration

  11. Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa

    Time frame: Over 3 hours post E.coli Bio- Particle administration

  12. Duodenal Impedance

    Time frame: Baseline

  13. Mean Serum Endotoxin (Bacterial LPS) Levels

    Time frame: Fasting, one time measurement after 8 hours

07

Results

Posted Aug 21, 2019

Participant flow

Participant flow — Overall Study
MilestoneHealthy VolunteersIBS-C
Started1920
Completed1819
Not completed11
Withdrew: Withdrawal by subject11

Outcome measures

PrimaryLactulose: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.

Time frame:
8-24 hr post test-dose administration
Reported as:
Mean · Ratio
Lactulose:C13 Mannitol Excretion Ratio 8-24hrs.
RatioHealthy VolunteersIBS - C
Lactulose:C13 Mannitol Excretion Ratio 8-24hrs.0.01 ± 0.0040.02 ± 0.005
Statistical analysis
  • Healthy Volunteers vs IBS - C · Wilcoxon (Mann-Whitney) · p = 0.87 · Mean difference (final values): 0.01
SecondaryLactose:C13 Mannitol Excretion Ratio 0-2hours
Time frame:
0-2 hr post-test dose administration
Reported as:
Mean · Ratio
Lactose:C13 Mannitol Excretion Ratio 0-2hours
RatioHealthy VolunteersIBS - C
Lactose:C13 Mannitol Excretion Ratio 0-2hours0.007 ± 0.00040.01 ± 0.001
SecondaryBaseline Transmucosal Resistance (TMR) of Duodenal Mucosa
Time frame:
Baseline
Reported as:
Mean · Ω*sq.cm
Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa
Ω*sq.cmHealthy VolunteersIBS - C
Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa29.8 ± 1.9428.16 ± 1.96
SecondaryCumulative 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.

Time frame:
3 hours post FITC-Dextran (4kDa) administration
Reported as:
Mean · ng/mL
Cumulative FITC-Dextran (4kDa) Concentration Across Duodenal Mucosa
ng/mLHealthy VolunteersIBS - C
Cumulative FITC-Dextran (4kDa) Concentration Across Duodenal Mucosa123.3 ± 24.29156.8 ± 33.73
SecondaryRate 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.

Time frame:
Over 3 hours post FITC-Dextran (4kDa) administration
Reported as:
Mean · ng/hr/sq.cm
Rate of FITC-Dextran (4kDa) Flux Across Duodenal Mucosa
ng/hr/sq.cmHealthy VolunteersIBS - C
Rate of FITC-Dextran (4kDa) Flux Across Duodenal Mucosa4980 ± 10446528 ± 1584
SecondaryBaseline Transmucosal Resistance (TMR) of Colonic Mucosa
Time frame:
Baseline
Reported as:
Mean · Ω*sq.cm
Baseline Transmucosal Resistance (TMR) of Colonic Mucosa
Ω*sq.cmHealthy VolunteersIBS - C
Baseline Transmucosal Resistance (TMR) of Colonic Mucosa17.60 ± 1.7019.06 ± 1.10
SecondaryCumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa
Time frame:
3 hours post FITC-Dextran (4kDa) administration
Reported as:
Mean · ng/mL
Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa
ng/mLHealthy VolunteersIBS - C
Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa132.2 ± 24.23122.5 ± 27.44
SecondaryRate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa
Time frame:
Over 3 hours post FITC-Dextran (4kDa) administration
Reported as:
Mean · ng/hr/sq.cm
Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa
ng/hr/sq.cmHealthy VolunteersIBS - C
Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa4931 ± 11566069 ± 1030
SecondaryCumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa
Time frame:
3 hours post E.coli Bio- Particle administration
Reported as:
Mean · CFU/ml
Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa
CFU/mlHealthy VolunteersIBS - C
Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa1.48*10^4 ± 2.6*10^31.82*10^4 ± 6.0*10^3
SecondaryRate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa
Time frame:
Over 3 hours post E.coli Bio- Particle administration
Reported as:
Mean · CFU/h/sq.cm
Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa
CFU/h/sq.cmHealthy VolunteersIBS - C
Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa5.42*10^5 ± 1.2*10^55.70*10^5 ± 1.90*10^5
SecondaryCumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa
Time frame:
3 hours post E.coli Bio- Particle administration
Reported as:
Mean · CFU/ml
Cumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa
CFU/mlHealthy VolunteersIBS - C
Cumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa1.07*10^4 ± 1.8*10^32.09*10^4 ± 6.8*10^3
SecondaryRate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa
Time frame:
Over 3 hours post E.coli Bio- Particle administration
Reported as:
Mean · CFU/h/sq.cm
Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa
CFU/h/sq.cmHealthy VolunteersIBS - C
Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa4.26*10^5 ± 5.3*10^47.67*10^5 ± 4.19*10^5
SecondaryDuodenal Impedance
Time frame:
Baseline
Reported as:
Mean · Ω
Duodenal Impedance
ΩHealthy VolunteersIBS - C
Duodenal Impedance705.9 ± 42.73729.5 ± 64.85
SecondaryMean Serum Endotoxin (Bacterial LPS) Levels
Time frame:
Fasting, one time measurement after 8 hours
Reported as:
Mean · EU/mL
Mean Serum Endotoxin (Bacterial LPS) Levels
EU/mLHealthy VolunteersIBS - C
Mean Serum Endotoxin (Bacterial LPS) Levels0.35 ± 0.020.36 ± 0.03

Adverse events

Collected over 15 months-from the first participant screening to the last participants completion date. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Healthy Volunteer0/18 (0%)0/18 (0%)0/18 (0%)
IBS-C0/19 (0%)0/19 (0%)1/19 (5.3%)
Most frequent other events
Most frequent other events
EventHealthy VolunteerIBS-C
Indigestion/HeartburnGastrointestinal disorders0/181/19

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Healthy VolunteersIBS-CTotal
<=18 years000
Between 18 and 65 years181937
>=65 years000
Age, Continuous
Age, Continuous(years)Healthy VolunteersIBS-CTotal
Mean45.37 ± 2.8243.06 ± 2.7844.24 ± 1.96
Sex: Female, Male
Sex: Female, Male(Participants)Healthy VolunteersIBS-CTotal
Female181937
Male000
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Healthy VolunteersIBS-CTotal
Hispanic or Latino000
Not Hispanic or Latino181937
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Healthy VolunteersIBS-CTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American000
White181937
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(Participants)Healthy VolunteersIBS-CTotal
United States181937
08

Study locations

1 site
  • Mayo Clinic in Rochester
    Rochester, Minnesota 55905, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 21, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02246647
Lead sponsor
Mayo Clinic
Collaborators
Takeda Pharmaceuticals International, Inc.
Responsible party
Madhusudan (Madhu) Grover, MBBS (Principal Investigator, Mayo Clinic) — Principal investigator
First posted
Sep 23, 2014
Start date
Sep 2014
Primary completion
Dec 8, 2016
Completion
Dec 8, 2016
Results posted
Aug 21, 2019
Last update
Aug 21, 2019

Study contacts

Madhusudan Grover, MBBS
principal investigator · Mayo Clinic

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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