The Effect of Dehydration on Intestinal Permeability

Study Overview
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Brief Summary
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In this study, the effect of dehydration by sauna exposure on the intestinal permeability in 20 healthy subjects is investigated. Participants attend three visits: 1) Sauna visit (to achieve 3% dehydration), 2) Positive control visit (intake of indomethacin which is known to increase intestinal permeability), 3) Negative control visit. At all visits, saliva samples, blood samples, faecal samples, saliva samples are collected and the multi-sugar permeability test is performed. In this test, participants drink a sugar solution and then urine collect urine for 5 and 24 h. The ratio of the sugars detected in the urine by liquid chromatography/mass spectometry is a reflection of the intestinal permeability. Saliva samples are collected for assessment of cortisol, a stress marker. Blood and faecal samples are collected for assessment of markers of intestinal barrier function and inflammation.

Official Title
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The Effect of Dehydration on Intestinal Permeability

Conditions
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Dehydration, Indomethacin

Intervention / Treatment
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* Other: Dehydration by sauna exposure
* Drug: Indomethacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent prior to any study related procedures Age > 18 till <50 Willing to abstain from probiotic products or medications known to alter gastrointestinal function throughout the study Exclusion Criteria: Abdominal surgery which might influence gastrointestinal function, except appendectomy and cholecystectomy. Current diagnosis of hypertension. Current diagnosis of psychiatric disease. Over 100kg or with a BMI over 35. Systemic use of steroids in the last 6 weeks. Use of antibiotics or antimicrobial medication in the last month. Daily usage of nonsteroidal anti-inflammatory drugs in the last 2 months or incidental use in the last 2 weeks prior to screening. Usage of medications that could affect the barrier function, except oral contraceptives, during the 14 days prior to screening. Diagnosed inflammatory gastrointestinal disease. Known organic gastrointestinal disease (e.g. irritable bowel syndrome, inflammatory bowel disease, chronic diarrhoea or constipation). History of or present gastrointestinal malignancy or polyposis. Recent (gastrointestinal) infection (within last 6 months). Eosinophilic disorders of the gastrointestinal tract. Current communicable disease (e.g. upper respiratory tract infection). Malignant disease and /or patients who are receiving systemic anti-neoplastic agents). Chronic neurological/neurodegenerative diseases (e.g. Parkinson's disease, multiple sclerosis). Autoimmune disease and/or patients receiving immunosuppressive medications. Major relevant allergies (e.g. food allergy, multiple allergies). Chronic pain syndromes (e.g. fibromyalgia) Chronic fatigue syndrome Regular use of probiotics in the last 6 weeks. Smoking and/or chewable tobacco. Planned changes to current diet or exercise regime. Use of laxatives, anti-diarrhetics, anti-cholinergics within last 4 weeks prior to screening. Use of immunosuppressant drugs within last 4 weeks prior to screening. Women: Pregnancy, lactation. Abuse of alcohol or drugs. Any disease/condition which in the investigator's opinion could interfere with the intestinal barrier function. Any clinically significant disease/condition which in the investigator's opinion could interfere with the results of the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dehydration by sauna exposure<br>Participants dehydrate using sauna exposure until they lose 3% of their body weight. | Other: Dehydration by sauna exposure<br>* Participants repeatedly undergo sauna exposures until they loose 3% of their body weight.<br>|
| Active Comparator: Indomethacin - Positive control<br>Indomethacin is administered to induce increased intestinal permeability | Drug: Indomethacin<br>* Participants take indomethacin in tablet form the evening before and the morning of the visit to induce intestinal permeability<br>|
| No Intervention: Negative control<br>No intervention is performed | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in small intestinal permeability measured as the urinary lactulose/rhamnose secretion ratio compared to negative control |  | 1-2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in whole gut permeability measured as the urinary sucralose/erythritol secretion ratio compared to negative control |  | 1-2 weeks | 
| Change in colonic permeability measured as the urinary sucralose/erythritol secretion ratio compared to negative control |  | 1-2 weeks | 
| Change in gastroduodenal permeability measured as urinary sucrose excretion |  | 1-2 weeks | 
| Change in quantity of intestinal permeability markers in blood | e.g. fatty acid binding proteins | 1-2 weeks | 
| Change in salivary cortisol levels |  | 1-2 weeks |