Bile Acid Malabsorption, Cholelithiasis
Conditions
Brief summary
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
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.
Interventions
1250 mg CDCA is given with a study meal
Sponsors
Zealand University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Stimulated Fibroblast Growth Factor 19 (FGF19) From Baseline Before Versus Post Cholecystectomy | baseline and 3 - 5 months after cholecystectomy | Change from baseline to after cholecystectomy in median chenodeoxycholic acid (CDCA) plus meal stimulated FGF19 (delta 0 min to 150 min after stimulation) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Chenodeoxycholic Acid (CDCA) Absorption to Plasma From Baseline Before Versus After Cholecystectomy | baseline and 3 - 5 months 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. |
| Change in Fasting 7-alpha-hydroxy-cholestenone (C4) From Baseline Before Versus After Cholecystectomy | baseline and 3 - 5 months after cholecystectomy | Change from baseline to after cholecystectomy in fasting C4 |
| Change in Lipid Status From Baseline Before Versus After Cholecystectomy | baseline and 3 - 5 months after cholecystectomy | Change from baseline to after cholecystectomy in plasma triglycerides |
| Change in Stool Frequency From Baseline Before Versus After Cholecystectomy | baseline and 3 - 5 months 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 |
| Change in Fasting FGF19 From Baseline Before Versus After Cholecystectomy | before and 3-5 months after cholecystectomy | change in fasting FGF19 before versus after cholecystectomy |
| Change in Patient Reported Diarrhea Symptoms Correlated With Change in C4 From Baseline Before Versus After Cholecystectomy | baseline and 3 - 5 months after cholecystectomy | Correlation between patient reported frequency of diarrhea (gastrointestinal quality of life index item 31) and fasting C4 before versus after cholecystectomy |
| Change in C4 Total Area Under the Curve From Baseline Before Versus After Cholecystectomy | before cholecystectomy and 3-5 months after cholecystectomy | Change in total AUC for C4 between visit 1 and visit 2 |
| Change in Patient Reported Diarrhea Symptoms Correlated With Change in FGF19 From Baseline Before Versus After Cholecystectomy | baseline and 3 - 5 months after cholecystectomy | Correlation between patient reported frequency of diarrhea (gastrointestinal quality of life index item 31) and fasting FGF19 before versus after cholecystectomy |
| Change in Stool Consistency (Bristol Stool Type) From Baseline Before Versus After Cholecystectomy | baseline and 3 - 5 months 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. |
| Change in Stool Pattern Correlated to FGF19 | baseline and 3 - 5 months after cholecystectomy | Spearman correlation between change from baseline to after cholecystectomy in FGF19 and in mean number of stools |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Visit 1 (Pro-operative) | intercurrent disease, drop-out before visit 1 | 1 |
| Visit 2 (Post-operative) | Adverse Event | 1 |
| Visit 2 (Post-operative) | Lost to Follow-up | 1 |
| Visit 2 (Post-operative) | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Intervention |
|---|---|
| Age, Continuous | 54 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 22 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Denmark | 22 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 18 |
| other Total, other adverse events | 22 / 22 | 15 / 18 |
| serious Total, serious adverse events | 0 / 22 | 0 / 18 |
Outcome results
Primary
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)
Time frame: baseline and 3 - 5 months after cholecystectomy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Visit 1 | Change in Stimulated Fibroblast Growth Factor 19 (FGF19) From Baseline Before Versus Post Cholecystectomy | 81 pg per mL |
| Visit 2 | Change in Stimulated Fibroblast Growth Factor 19 (FGF19) From Baseline Before Versus Post Cholecystectomy | 186 pg per mL |
p-value: 0.03Wilcoxon (Mann-Whitney)
Secondary
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
Time frame: before cholecystectomy and 3-5 months after cholecystectomy
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visit 1 | Change in C4 Total Area Under the Curve From Baseline Before Versus After Cholecystectomy | 774 ng/mL x minutes |
| Visit 2 | Change in C4 Total Area Under the Curve From Baseline Before Versus After Cholecystectomy | 1040 ng/mL x minutes |
p-value: 0.36paired t-test
Secondary
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.
Time frame: baseline and 3 - 5 months after cholecystectomy
Population: compares visit 1 with visit 2
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Visit 1 | Change in Chenodeoxycholic Acid (CDCA) Absorption to Plasma From Baseline Before Versus After Cholecystectomy | 1554 µM * minutes |
| Visit 2 | Change in Chenodeoxycholic Acid (CDCA) Absorption to Plasma From Baseline Before Versus After Cholecystectomy | 1847 µM * minutes |
Secondary
Change in Fasting 7-alpha-hydroxy-cholestenone (C4) From Baseline Before Versus After Cholecystectomy
Change from baseline to after cholecystectomy in fasting C4
Time frame: baseline and 3 - 5 months after cholecystectomy
Population: paired t-test of lognormalized values
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visit 1 | Change in Fasting 7-alpha-hydroxy-cholestenone (C4) From Baseline Before Versus After Cholecystectomy | 6.0 ng/mL |
| Visit 2 | Change in Fasting 7-alpha-hydroxy-cholestenone (C4) From Baseline Before Versus After Cholecystectomy | 7.5 ng/mL |
Comparison: compares visit 1 with visit 2p-value: 0.63paired t-test
Secondary
Change in Fasting FGF19 From Baseline Before Versus After Cholecystectomy
change in fasting FGF19 before versus after cholecystectomy
Time frame: before and 3-5 months after cholecystectomy
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Visit 1 | Change in Fasting FGF19 From Baseline Before Versus After Cholecystectomy | 102 pg per mL |
| Visit 2 | Change in Fasting FGF19 From Baseline Before Versus After Cholecystectomy | 92 pg per mL |
p-value: 0.29paired t-test
Secondary
Change in Lipid Status From Baseline Before Versus After Cholecystectomy
Change from baseline to after cholecystectomy in plasma triglycerides
Time frame: baseline and 3 - 5 months after cholecystectomy
Population: visit 1 compared with visit 2
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Visit 1 | Change in Lipid Status From Baseline Before Versus After Cholecystectomy | 1.4 mmol/L |
| Visit 2 | Change in Lipid Status From Baseline Before Versus After Cholecystectomy | 1.5 mmol/L |
p-value: 0.32Wilcoxon (Mann-Whitney)
Secondary
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
Time frame: baseline and 3 - 5 months after cholecystectomy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Visit 1 | Change in Patient Reported Diarrhea Symptoms Correlated With Change in C4 From Baseline Before Versus After Cholecystectomy | -.23 Spearman correlation coefficient |
| Visit 2 | Change in Patient Reported Diarrhea Symptoms Correlated With Change in C4 From Baseline Before Versus After Cholecystectomy | -0.52 Spearman correlation coefficient |
p-value: 0.35Spearman correlation
p-value: 0.03Spearman correlation
Secondary
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
Time frame: baseline and 3 - 5 months after cholecystectomy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Visit 1 | Change in Patient Reported Diarrhea Symptoms Correlated With Change in FGF19 From Baseline Before Versus After Cholecystectomy | 0.08 Spearman correlation coefficient |
| Visit 2 | Change in Patient Reported Diarrhea Symptoms Correlated With Change in FGF19 From Baseline Before Versus After Cholecystectomy | -0.07 Spearman correlation coefficient |
p-value: 0.73Spearman correlation
p-value: 0.77Spearman correlation
Secondary
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.
Time frame: baseline and 3 - 5 months after cholecystectomy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Visit 1 | Change in Stool Consistency (Bristol Stool Type) From Baseline Before Versus After Cholecystectomy | 4.2 Bristol stool type |
| Visit 2 | Change in Stool Consistency (Bristol Stool Type) From Baseline Before Versus After Cholecystectomy | 4.0 Bristol stool type |
p-value: 0.8Wilcoxon (Mann-Whitney)
Secondary
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
Time frame: baseline and 3 - 5 months after cholecystectomy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Visit 1 | Change in Stool Frequency From Baseline Before Versus After Cholecystectomy | 1.6 mean stools per day |
| Visit 2 | Change in Stool Frequency From Baseline Before Versus After Cholecystectomy | 1.6 mean stools per day |
p-value: 0.73Wilcoxon (Mann-Whitney)
Secondary
Change in Stool Pattern Correlated to FGF19
Spearman correlation between change from baseline to after cholecystectomy in FGF19 and in mean number of stools
Time frame: baseline and 3 - 5 months after cholecystectomy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Visit 1 | Change in Stool Pattern Correlated to FGF19 | -0.21 Spearman correlation coefficient |
p-value: 0.41Spearman correlation