A Phase 4 interventional study of chenodeoxycholic acid in Bile Acid Malabsorption and Cholelithiasis, sponsored by Zealand University Hospital. Completed at 1 site in Denmark. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2022-05-19.
Sponsored by Zealand University Hospital · Phase 4, Interventional, and Diagnostic
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
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.
Exclusion Criteria:
chenodeoxycholic acid 1250mg po.
Drug: chenodeoxycholic acid
1250 mg CDCA is given with a study meal
Also known as: CDCA, chenodeoxycholate
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
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
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
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
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
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
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
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
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
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
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
| Milestone | Intervention |
|---|---|
| Started | 23 |
| Completed | 22 |
| Not completed | 1 |
| Withdrew: Intercurrent disease, drop-out before visit 1 | 1 |
| Milestone | Intervention |
|---|---|
| Started | 22 |
| Completed | 18 |
| Not completed | 4 |
| Withdrew: Lost to follow-up | 1 |
| Withdrew: Adverse event | 1 |
| Withdrew: Withdrawal by subject | 2 |
Change from baseline to after cholecystectomy in median chenodeoxycholic acid (CDCA) plus meal stimulated FGF19 (delta 0 min to 150 min after stimulation)
| pg per mL | Visit 1 | Visit 2 |
|---|---|---|
| Change in Stimulated Fibroblast Growth Factor 19 (FGF19) From Baseline Before Versus Post Cholecystectomy | 81 (-20 to 274) | 186 (111 to 382) |
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.
| µM * minutes | Visit 1 | Visit 2 |
|---|---|---|
| Change in Chenodeoxycholic Acid (CDCA) Absorption to Plasma From Baseline Before Versus After Cholecystectomy | 1554 (1084 to 2231) | 1847 (1310 to 2193) |
Change from baseline to after cholecystectomy in fasting C4
| ng/mL | Visit 1 | Visit 2 |
|---|---|---|
| Change in Fasting 7-alpha-hydroxy-cholestenone (C4) From Baseline Before Versus After Cholecystectomy | 6.0 (4.1 to 8.7) | 7.5 (5.5 to 10.0) |
Change from baseline to after cholecystectomy in plasma triglycerides
| mmol/L | Visit 1 | Visit 2 |
|---|---|---|
| Change in Lipid Status From Baseline Before Versus After Cholecystectomy | 1.4 (1.1 to 2.1) | 1.5 (1.1 to 1.9) |
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
| mean stools per day | Visit 1 | Visit 2 |
|---|---|---|
| Change in Stool Frequency From Baseline Before Versus After Cholecystectomy | 1.6 (1.1 to 2.0) | 1.6 (1.3 to 1.7) |
Spearman correlation between change from baseline to after cholecystectomy in FGF19 and in mean number of stools
| Spearman correlation coefficient | Intervention |
|---|---|
| Change in Stool Pattern Correlated to FGF19 | -0.21 |
Correlation between patient reported frequency of diarrhea (gastrointestinal quality of life index item 31) and fasting C4 before versus after cholecystectomy
| Spearman correlation coefficient | Visit 1 | Visit 2 |
|---|---|---|
| Change in Patient Reported Diarrhea Symptoms Correlated With Change in C4 From Baseline Before Versus After Cholecystectomy | -.23 | -0.52 |
Change in total AUC for C4 between visit 1 and visit 2
| ng/mL x minutes | Visit 1 | Visit 2 |
|---|---|---|
| Change in C4 Total Area Under the Curve From Baseline Before Versus After Cholecystectomy | 774 (524 to 1143) | 1040 (765 to 1417) |
change in fasting FGF19 before versus after cholecystectomy
| pg per mL | Visit 1 | Visit 2 |
|---|---|---|
| Change in Fasting FGF19 From Baseline Before Versus After Cholecystectomy | 102 (74 to 141) | 92 (67 to 125) |
Correlation between patient reported frequency of diarrhea (gastrointestinal quality of life index item 31) and fasting FGF19 before versus after cholecystectomy
| Spearman correlation coefficient | Visit 1 | Visit 2 |
|---|---|---|
| Change in Patient Reported Diarrhea Symptoms Correlated With Change in FGF19 From Baseline Before Versus After Cholecystectomy | 0.08 | -0.07 |
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.
| Bristol stool type | Visit 1 | Visit 2 |
|---|---|---|
| Change in Stool Consistency (Bristol Stool Type) From Baseline Before Versus After Cholecystectomy | 4.2 (3.7 to 4.8) | 4.0 (3.6 to 4.5) |
Collected over Adverse events were registered in relation to administration of chenodeoxycholic acid both at visit 1 and visit 2 (separated by 3-5 months). Registration started at time of administration of chenodeoxycholic acid (one dose) and the registration lasted four days after this. At day three after the administration standard liver biochemistry was measured (ALT, Alk. phospatase, INR, bilirubin).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Visit 1 | 0/22 (0%) | 0/22 (0%) | 22/22 (100%) |
| Visit 2 | 0/18 (0%) | 0/18 (0%) | 15/18 (83.3%) |
| Event | Visit 1 | Visit 2 |
|---|---|---|
| DiarrheaGastrointestinal disorders | 14/22 | 14/18 |
| Abdominal painGastrointestinal disorders | 3/22 | 5/18 |
| Abdominal sounds/growlingGastrointestinal disorders | 5/22 | 2/18 |
| NauseaGastrointestinal disorders | 3/22 | 1/18 |
| FatigueGeneral disorders | 2/22 | 0/18 |
| Abdominal bloatingGastrointestinal disorders | 1/22 | 1/18 |
| HeartburnGastrointestinal disorders | 1/22 | 1/18 |
| HeadacheNervous system disorders | 1/22 | 0/18 |
| MigraineNervous system disorders | 1/22 | 0/18 |
| DizzynessNervous system disorders | 1/22 | 0/18 |
23 patients enrolled but one dropped out before visit 1. Baseline characteristics therefore only are available for 22
| Age, Continuous(years) | Intervention |
|---|---|
| Median | 54 (38 to 59) |
| Sex: Female, Male(Participants) | Intervention |
|---|---|
| Female | 10 |
| Male | 12 |
| Race (NIH/OMB)(Participants) | Intervention |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 0 |
| More than one race | 0 |
| Unknown or Not Reported | 22 |
| Region of Enrollment(participants) | Intervention |
|---|---|
| Denmark | 22 |
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Zealand University Hospital