Changes in Bile Acid Homeostasis and Stool Habits After Cholecystectomy

Study Overview
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Brief Summary
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Investigate serial plasma samples of fibroblast growth factor 19 (FGF19) after oral stimulation with chenodeoxycholic acid in the same subjects before and after elective cholecystectomy

Detailed Description
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Lack of FGF19 and elevated 7-alpha-hydroxy-colestenone (C4) is associated with the bile acid diarrhoea (BAD), a disease with increasing estimated of prevalence. BAD is occasionally triggered by cholecystectomy and FGF19 and C4 is known to be affected by cholecystectomy. The investigators are exploring if FGF19 after oral stimulation can be developed to a universal test for BAD, and need to know how the proposed test is affected by cholecystectomy.

Official Title
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Changes in Bile Acid Homeostasis and Stool Habits After Cholecystectomy

Conditions
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Bile Acid Malabsorption, Cholelithiasis

Intervention / Treatment
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* Drug: chenodeoxycholic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: planned elective cholecystectomy Exclusion Criteria: small bowel resection right sided hemicolectomy known chronic diarrheal disease (celiac disease, lactose malabsorption, Inflammatory bowel diseases, incl microscopic colitis) pregnancy wish for pregnancy within next three months allergy to eggs allergy to constituents in Xenbilox (capsules with chenodeoxycholic acid) acute cholecystitis within two months chronic cholecystitis cirrhosis of the liver suspected obstructive choledocholithiasis icterus

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>chenodeoxycholic acid 1250mg po. | Drug: chenodeoxycholic acid<br>* 1250 mg CDCA is given with a study meal<br>* Other names: chenodeoxycholate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Stimulated Fibroblast Growth Factor 19 (FGF19) From Baseline Before Versus Post Cholecystectomy | Change from baseline to after cholecystectomy in median chenodeoxycholic acid (CDCA) plus meal stimulated FGF19 (delta 0 min to 150 min after stimulation) | baseline and 3 - 5 months after cholecystectomy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Chenodeoxycholic Acid (CDCA) Absorption to Plasma From Baseline Before Versus After Cholecystectomy | Change from baseline to after cholecystectomy in median unconjugated CDCA plus meal stimulated absorption of unconjugated CDCA to measured in plasma (total area under the CDCA curve with measurement at fasting ie. t=0 minutes and subsequently at 60, 90, 120, and finally at 150minutes. | baseline and 3 - 5 months after cholecystectomy | 
| Change in Fasting 7-alpha-hydroxy-cholestenone (C4) From Baseline Before Versus After Cholecystectomy | Change from baseline to after cholecystectomy in fasting C4 | baseline and 3 - 5 months after cholecystectomy | 
| Change in Lipid Status From Baseline Before Versus After Cholecystectomy | Change from baseline to after cholecystectomy in plasma triglycerides | baseline and 3 - 5 months after cholecystectomy | 
| Change in Stool Frequency From Baseline Before Versus After Cholecystectomy | Change from baseline to after cholecystectomy in number of stools as a mean of a seven-day diary baseline versus after cholecystectomy. That is the diary results for each study participant is tallied using mean values. The tallying of these diary results is done using medians. Therefore the unit used is 'mean stools per day' and this is reported with medians | baseline and 3 - 5 months after cholecystectomy | 
| Change in Stool Pattern Correlated to FGF19 | Spearman correlation between change from baseline to after cholecystectomy in FGF19 and in mean number of stools | baseline and 3 - 5 months after cholecystectomy | 
| Change in Patient Reported Diarrhea Symptoms Correlated With Change in C4 From Baseline Before Versus After Cholecystectomy | Correlation between patient reported frequency of diarrhea (gastrointestinal quality of life index item 31) and fasting C4 before versus after cholecystectomy | baseline and 3 - 5 months after cholecystectomy | 
| Change in C4 Total Area Under the Curve From Baseline Before Versus After Cholecystectomy | Change in total AUC for C4 between visit 1 and visit 2 | before cholecystectomy and 3-5 months after cholecystectomy | 
| Change in Fasting FGF19 From Baseline Before Versus After Cholecystectomy | change in fasting FGF19 before versus after cholecystectomy | before and 3-5 months after cholecystectomy | 
| Change in Patient Reported Diarrhea Symptoms Correlated With Change in FGF19 From Baseline Before Versus After Cholecystectomy | Correlation between patient reported frequency of diarrhea (gastrointestinal quality of life index item 31) and fasting FGF19 before versus after cholecystectomy | baseline and 3 - 5 months after cholecystectomy | 
| Change in Stool Consistency (Bristol Stool Type) From Baseline Before Versus After Cholecystectomy | Change from baseline to after cholecystectomy in mean Bristol type per stool as of a seven-day diary baseline versus after cholecystectomy. The Bristol scale divides stool into seven categories from 1 (hard lumps) to 7 (completely watery stool). The diary shows pictograms with short text descriptions. | baseline and 3 - 5 months after cholecystectomy |