Gut Transit Effect on Enterohepatic Circulation

Study Overview
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Brief Summary
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A study to determine the influence of changing intestinal transit time of the enterohepatic recirculation of bile acids.

Detailed Description
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The digestion of food by human body starts from oral cavity and continues until its excreted as faeces. There are different factors affecting this process. Important factors are movement through the GI Tract, breakdown of food material and absorption by the body to produce energy. The unabsorbed waste material is then excreted by the body. Different enzymes are produced by human body which are responsible for digestion of food. One important chemical is bile which is produced in the gall bladder. It is important in digestion of fatty foods but affects the movement of food material as well. There are numerous bacteria present in human GI tract especially in mouth and large bowel which also play an important role in process of digestion of food. Different conditions of health and disease can affect how food moves through the GI tract (known as intestinal transit). It also affects the activity of different digestive enzymes and chemicals in body. The bacterial population in the body is also affected by changes described above. The purpose of this study is to observe how these different processes especially the intestinal transit, bile salts and gut bacteria affect each other. This will help to identify mechanisms responsible for different disorders of human gut like irritable bowel syndrome. The study is part of an effort to identify new and future treatment of these conditions.

Official Title
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The Effect of Intestinal Transit on the Entrohepatic Circulation of Bile Salts, Faecal Microbiome and Production of Volatile Organic Compounds

Conditions
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Intestinal Transit

Intervention / Treatment
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* Drug: Loperamide
* Drug: Senna


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Healthy volunteers between the ages of 18 and 65 Exclusion Criteria: Unable to consent Pregnant or lactating Known diarrhoeal disorder Known constipation. Any gastrointestinal disease or previous gastric surgery An episode of gastroenteritis within the last month Taking any acid suppressing medication Any significant medical condition (e.g. diabetes, renal disease) Any antibiotic intake within the last one-month Any drug with known effects on GI motility Known allergy or intolerance to senna or loperamide

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomised cross-over study. Volunteers will be assessed at baseline, then after either taking loperamide or senna at the maximally tolerated dose for 2 days prior to the 'assessment period' then during the assessment period (5-7 days). After a washout period of at least 21 days, volunteers will then repeat the same assessments but cross over to take the second drug either loperamide or senna.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: loperamide<br>Slows intestinal transit time | Drug: Loperamide<br>* Alters intestinal transit time.<br>|
| Experimental: senna<br>Speeds up intestinal transit time | Drug: Senna<br>* Alters intestinal transit time.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of intestinal transit on faecal bile acids | Change in bile acid pool and activity from baseline with each intervention | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stool bacterial count | Bacterial count | 7 days | 
| 1. common stool test | calprotectin | 7 days | 
| 2. common stool test | elastase | 7 days | 
| 3. common stool test | lactoferrin | 7 days | 
| Volatile Organic Compounds | VOC estimation in urine | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intestinal Transit, Bile Salts, Gut Bacteria, Volatile Organic Compounds