The Effect of Dehydration on Intestinal Permeability

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.

Study Overview

• Status: Completed
• Conditions: Dehydration; Indomethacin
• Intervention / Treatment: Other: Dehydration by sauna exposure; Drug: Indomethacin

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Örebro County
    • Örebro, Örebro County, Sweden, 70182
      • Örebro University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent prior to any study related procedures
2. Age > 18 till <50
3. Willing to abstain from probiotic products or medications known to alter gastrointestinal function throughout the study

Exclusion Criteria:

1. Abdominal surgery which might influence gastrointestinal function, except appendectomy and cholecystectomy.
2. Current diagnosis of hypertension.
3. Current diagnosis of psychiatric disease.
4. Over 100kg or with a BMI over 35.
5. Systemic use of steroids in the last 6 weeks.
6. Use of antibiotics or antimicrobial medication in the last month.
7. Daily usage of nonsteroidal anti-inflammatory drugs in the last 2 months or incidental use in the last 2 weeks prior to screening.
8. Usage of medications that could affect the barrier function, except oral contraceptives, during the 14 days prior to screening.
9. Diagnosed inflammatory gastrointestinal disease.
10. Known organic gastrointestinal disease (e.g. irritable bowel syndrome, inflammatory bowel disease, chronic diarrhoea or constipation).
11. History of or present gastrointestinal malignancy or polyposis.
12. Recent (gastrointestinal) infection (within last 6 months).
13. Eosinophilic disorders of the gastrointestinal tract.
14. Current communicable disease (e.g. upper respiratory tract infection).
15. Malignant disease and /or patients who are receiving systemic anti-neoplastic agents).
16. Chronic neurological/neurodegenerative diseases (e.g. Parkinson's disease, multiple sclerosis).
17. Autoimmune disease and/or patients receiving immunosuppressive medications.
18. Major relevant allergies (e.g. food allergy, multiple allergies).
19. Chronic pain syndromes (e.g. fibromyalgia)
20. Chronic fatigue syndrome
21. Regular use of probiotics in the last 6 weeks.
22. Smoking and/or chewable tobacco.
23. Planned changes to current diet or exercise regime.
24. Use of laxatives, anti-diarrhetics, anti-cholinergics within last 4 weeks prior to screening.
25. Use of immunosuppressant drugs within last 4 weeks prior to screening.
26. Women: Pregnancy, lactation.
27. Abuse of alcohol or drugs.
28. Any disease/condition which in the investigator's opinion could interfere with the intestinal barrier function.
29. Any clinically significant disease/condition which in the investigator's opinion could interfere with the results of the trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Örebro University, Sweden

Publications and helpful links

General Publications

• Roca Rubio MF, Eriksson U, Brummer RJ, Konig J. Sauna dehydration as a new physiological challenge model for intestinal barrier function. Sci Rep. 2021 Jul 30;11(1):15514. doi: 10.1038/s41598-021-94814-0.

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2018
• Primary Completion (Actual): June 21, 2018
• Study Completion (Actual): June 21, 2018

Study Registration Dates

• First Submitted: July 30, 2018
• First Submitted That Met QC Criteria: August 2, 2018
• First Posted (Actual): August 8, 2018

Study Record Updates

• Last Update Posted (Actual): August 8, 2018
• Last Update Submitted That Met QC Criteria: August 2, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Water-Electrolyte Imbalance; Dehydration; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Reproductive Control Agents; Gout Suppressants; Tocolytic Agents; Indomethacin
• Other Study ID Numbers: 2017/463

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No individual participant data will be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No