Trial Outcomes & Findings for Biomarkers for Intestinal Permeability in Patients With Constipation (NCT NCT02246647)

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

39 participants

Primary outcome timeframe

8-24 hr post test-dose administration

Results posted on

2019-08-21

Participant Flow

Participant milestones

Participant milestones
Measure	Healthy Volunteers Healthy subjects ages 18 - 65 Must not have had any abdominal surgeries, IBS, IBD, microscopic colitis or celiac disease. Must not have used tobacco products in the last 6 months. Must not have used corticosteroids in the last 6 weeks. Must not have taken any treatment specifically taken for IBS, including loperamide, cholestyramine, alosetron . Must not be taking any drugs with a known pharmacological activity at 5-HT4, 5-HT2b or 5-HT3 receptors. Must not have taken anti-cholinergic agents (e.g. dicyclomine, hyoscyamine, propantheline), Ultram. No 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. Must not have a bleeding disorder or medications that incr	IBS-C Age (yr) 18 to 65 Must have IBS-C by Rome III criteria No abdominal surgery (except appendectomy and cholecystectomy) Exclusion criteria: Must have no History of IBD (Crohn's disease or ulcerative colitis), microscopic colitis or celiac disease. Use of tobacco products within the past 6 months (since nicotine may affect intestinal permeability) Use of NSAIDs or aspirin within the past week (since NSAIDs affect intestinal permeability) Use of oral corticosteroids within the previous 6 weeks No Ingestion of artificial sweeteners such as SplendaTM (sucralose), NutraSweet TM(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 ny treatment specifically taken for IBS, including loperamide, cholestyramine, alosetron No drugs with a known pharmacological activity at 5
Overall Study STARTED	19	20
Overall Study COMPLETED	18	19
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Healthy Volunteers Healthy subjects ages 18 - 65 Must not have had any abdominal surgeries, IBS, IBD, microscopic colitis or celiac disease. Must not have used tobacco products in the last 6 months. Must not have used corticosteroids in the last 6 weeks. Must not have taken any treatment specifically taken for IBS, including loperamide, cholestyramine, alosetron . Must not be taking any drugs with a known pharmacological activity at 5-HT4, 5-HT2b or 5-HT3 receptors. Must not have taken anti-cholinergic agents (e.g. dicyclomine, hyoscyamine, propantheline), Ultram. No 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. Must not have a bleeding disorder or medications that incr	IBS-C Age (yr) 18 to 65 Must have IBS-C by Rome III criteria No abdominal surgery (except appendectomy and cholecystectomy) Exclusion criteria: Must have no History of IBD (Crohn's disease or ulcerative colitis), microscopic colitis or celiac disease. Use of tobacco products within the past 6 months (since nicotine may affect intestinal permeability) Use of NSAIDs or aspirin within the past week (since NSAIDs affect intestinal permeability) Use of oral corticosteroids within the previous 6 weeks No Ingestion of artificial sweeteners such as SplendaTM (sucralose), NutraSweet TM(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 ny treatment specifically taken for IBS, including loperamide, cholestyramine, alosetron No drugs with a known pharmacological activity at 5
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

Biomarkers for Intestinal Permeability in Patients With Constipation

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=18 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers. Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.	IBS - C n=19 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases. Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.
Lactulose:C13 Mannitol Excretion Ratio 8-24hrs.	0.01 Ratio Standard Error 0.004	0.02 Ratio Standard Error 0.005

SECONDARY outcome

Timeframe: 0-2 hr post-test dose administration

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=18 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers. Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.	IBS - C n=19 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases. Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.
Lactose:C13 Mannitol Excretion Ratio 0-2hours	0.007 Ratio Standard Error 0.0004	0.01 Ratio Standard Error 0.001

SECONDARY outcome

Timeframe: Baseline

Population: Two participants ( 1 in Healthy volunteers and 1 in IBS-C ) were not analysed for the Baseline transmucosal resistance (TMR) of duodenal mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure etc.

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=17 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers. Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.	IBS - C n=18 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases. Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.
Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa	29.8 Ω*sq.cm Standard Error 1.94	28.16 Ω*sq.cm Standard Error 1.96

SECONDARY outcome

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

Population: Four participants (2 in Healthy volunteers and 2 in IBS-C) were not analysed for the Cumulative FITC-Dextran (4kDa) concentration across duodenal mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.

This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=16 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers. Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.	IBS - C n=17 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases. Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.
Cumulative FITC-Dextran (4kDa) Concentration Across Duodenal Mucosa	123.3 ng/mL Standard Error 24.29	156.8 ng/mL Standard Error 33.73

SECONDARY outcome

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

Population: Four participants ( 2 in Healthy volunteers and 2 in IBS-C ) were not analysed for the Rate of FITC-Dextran (4kDa) flux across duodenal mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure etc.

This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=16 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers. Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.	IBS - C n=17 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases. Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.
Rate of FITC-Dextran (4kDa) Flux Across Duodenal Mucosa	4980 ng/hr/sq.cm Standard Error 1044	6528 ng/hr/sq.cm Standard Error 1584

SECONDARY outcome

Timeframe: Baseline

Population: One participant in IBS-C was not analysed for the Baseline Transmucosal Resistance (TMR) of Colonic Mucosa due to various reasons such inadequate size of the biopsy specimen.

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=18 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers. Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.	IBS - C n=18 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases. Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.
Baseline Transmucosal Resistance (TMR) of Colonic Mucosa	17.60 Ω*sq.cm Standard Error 1.70	19.06 Ω*sq.cm Standard Error 1.10

SECONDARY outcome

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

Population: 7 participants (2 in Healthy volunteers and 5 in IBS-C) were not analysed for the Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=16 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers. Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.	IBS - C n=14 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases. Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.
Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa	132.2 ng/mL Standard Error 24.23	122.5 ng/mL Standard Error 27.44

SECONDARY outcome

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

Population: 7 participants (2 in Healthy volunteers and 5 in IBS-C) were not analysed for the Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=16 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers. Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.	IBS - C n=14 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases. Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.
Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa	4931 ng/hr/sq.cm Standard Error 1156	6069 ng/hr/sq.cm Standard Error 1030

SECONDARY outcome

Timeframe: 3 hours post E.coli Bio- Particle administration

Population: 11 participants (4 in Healthy volunteers and 7 in IBS-C) were not analysed for Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=14 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers. Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.	IBS - C n=12 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases. Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.
Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa	1.4810^4 CFU/ml Standard Error 2.610^3	1.8210^4 CFU/ml Standard Error 6.010^3

SECONDARY outcome

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

Population: 11 participants (4 in Healthy volunteers and 7 in IBS-C) were not analysed for Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=14 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers. Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.	IBS - C n=12 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases. Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.
Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa	5.4210^5 CFU/h/sq.cm Standard Error 1.210^5	5.7010^5 CFU/h/sq.cm Standard Error 1.9010^5

SECONDARY outcome

Timeframe: 3 hours post E.coli Bio- Particle administration

Population: 7 participants (2 in Healthy volunteers and 5 in IBS-C) were not analysed for Cumulative E.coli Bio- Particle K12 Concentration Across Colonic Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=16 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers. Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.	IBS - C n=14 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases. Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.
Cumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa	1.0710^4 CFU/ml Standard Error 1.810^3	2.0910^4 CFU/ml Standard Error 6.810^3

SECONDARY outcome

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

Population: 7 participants (2 in Healthy volunteers and 5 in IBS-C) were not analysed for Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=16 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers. Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.	IBS - C n=14 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases. Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.
Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa	4.2610^5 CFU/h/sq.cm Standard Error 5.310^4	7.6710^5 CFU/h/sq.cm Standard Error 4.1910^5

SECONDARY outcome

Timeframe: Baseline

Population: 12 participants (2 in Healthy volunteers and 10 in IBS-C) were not analysed for Duodenal impedance due to various reasons such inadequate size of the biopsy specimen, participant did not show up for the procedure, etc.

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=16 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers. Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.	IBS - C n=9 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases. Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.
Duodenal Impedance	705.9 Ω Standard Error 42.73	729.5 Ω Standard Error 64.85

SECONDARY outcome

Timeframe: Fasting, one time measurement after 8 hours

Population: 2 participants (1 in healthy volunteers and 1 in IBS-C) were not analysed for Mean Serum Endotoxin (Bacterial LPS) Levels due to various reasons such as non-availability of the blood sample, technical errors, etc.

Outcome measures

Outcome measures
Measure	Healthy Volunteers n=17 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from Healthy Volunteers. Flexible sigmoidoscopy: Colonic biopsies will be collected from Healthy Volunteers.	IBS - C n=18 Participants Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and (non-radioactive) 13C labeled mannitol, 100 mg and sucralose, 50 mg) in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy Esophagogastroduodenoscopy: Duodenal biopsies will be collected from IBS - C cases. Flexible sigmoidoscopy: Colonic biopsies will be collected from IBS - C cases.
Mean Serum Endotoxin (Bacterial LPS) Levels	0.35 EU/mL Standard Error 0.02	0.36 EU/mL Standard Error 0.03

Adverse Events

Healthy Volunteer

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

IBS-C

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Healthy Volunteer n=18 participants at risk Healthy volunteers between ages 18 - 65, who have no history of IBS.	IBS-C n=19 participants at risk ROME III IBS-C patients
Gastrointestinal disorders Indigestion/Heartburn	0.00% 0/18 • 15 months-from the first participant screening to the last participants completion date	5.3% 1/19 • Number of events 1 • 15 months-from the first participant screening to the last participants completion date

Additional Information

Madhusudan Grover, MBBS

Mayo Clinic

Phone: 507-253-5384

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Healthy Volunteers n=18 Participants Healthy volunteers between ages 18 - 65, who have not history of IBS.	IBS-C n=19 Participants Volunteers who have been diagnosed with IBS - Constipation (IBS-C)	Total n=37 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	45.37 years STANDARD_DEVIATION 2.82 • n=5 Participants	43.06 years STANDARD_DEVIATION 2.78 • n=7 Participants	44.24 years STANDARD_DEVIATION 1.96 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	18 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants