Trial Outcomes & Findings for Changes in Bile Acid Homeostasis and Stool Habits After Cholecystectomy (NCT NCT03168555)
NCT ID: NCT03168555
Last Updated: 2022-05-19
Results Overview
Change from baseline to after cholecystectomy in median chenodeoxycholic acid (CDCA) plus meal stimulated FGF19 (delta 0 min to 150 min after stimulation)
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
23 participants
Primary outcome timeframe
baseline and 3 - 5 months after cholecystectomy
Results posted on
2022-05-19
Participant Flow
Participant milestones
| Measure |
Intervention
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
|---|---|
|
Visit 1 (Pro-operative)
STARTED
|
23
|
|
Visit 1 (Pro-operative)
COMPLETED
|
22
|
|
Visit 1 (Pro-operative)
NOT COMPLETED
|
1
|
|
Visit 2 (Post-operative)
STARTED
|
22
|
|
Visit 2 (Post-operative)
COMPLETED
|
18
|
|
Visit 2 (Post-operative)
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Intervention
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
|---|---|
|
Visit 1 (Pro-operative)
intercurrent disease, drop-out before visit 1
|
1
|
|
Visit 2 (Post-operative)
Lost to Follow-up
|
1
|
|
Visit 2 (Post-operative)
Adverse Event
|
1
|
|
Visit 2 (Post-operative)
Withdrawal by Subject
|
2
|
Baseline Characteristics
Changes in Bile Acid Homeostasis and Stool Habits After Cholecystectomy
Baseline characteristics by cohort
| Measure |
Intervention
n=22 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
|---|---|
|
Age, Continuous
|
54 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
22 Participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
22 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: baseline and 3 - 5 months after cholecystectomyChange from baseline to after cholecystectomy in median chenodeoxycholic acid (CDCA) plus meal stimulated FGF19 (delta 0 min to 150 min after stimulation)
Outcome measures
| Measure |
Visit 1
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
Visit 2
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
|---|---|---|
|
Change in Stimulated Fibroblast Growth Factor 19 (FGF19) From Baseline Before Versus Post Cholecystectomy
|
81 pg per mL
Interval -20.0 to 274.0
|
186 pg per mL
Interval 111.0 to 382.0
|
SECONDARY outcome
Timeframe: baseline and 3 - 5 months after cholecystectomyPopulation: compares visit 1 with visit 2
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.
Outcome measures
| Measure |
Visit 1
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
Visit 2
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
|---|---|---|
|
Change in Chenodeoxycholic Acid (CDCA) Absorption to Plasma From Baseline Before Versus After Cholecystectomy
|
1554 µM * minutes
Interval 1084.0 to 2231.0
|
1847 µM * minutes
Interval 1310.0 to 2193.0
|
SECONDARY outcome
Timeframe: baseline and 3 - 5 months after cholecystectomyPopulation: paired t-test of lognormalized values
Change from baseline to after cholecystectomy in fasting C4
Outcome measures
| Measure |
Visit 1
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
Visit 2
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
|---|---|---|
|
Change in Fasting 7-alpha-hydroxy-cholestenone (C4) From Baseline Before Versus After Cholecystectomy
|
6.0 ng/mL
Interval 4.1 to 8.7
|
7.5 ng/mL
Interval 5.5 to 10.0
|
SECONDARY outcome
Timeframe: baseline and 3 - 5 months after cholecystectomyPopulation: visit 1 compared with visit 2
Change from baseline to after cholecystectomy in plasma triglycerides
Outcome measures
| Measure |
Visit 1
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
Visit 2
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
|---|---|---|
|
Change in Lipid Status From Baseline Before Versus After Cholecystectomy
|
1.4 mmol/L
Interval 1.1 to 2.1
|
1.5 mmol/L
Interval 1.1 to 1.9
|
SECONDARY outcome
Timeframe: baseline and 3 - 5 months after cholecystectomyChange 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
Outcome measures
| Measure |
Visit 1
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
Visit 2
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
|---|---|---|
|
Change in Stool Frequency From Baseline Before Versus After Cholecystectomy
|
1.6 mean stools per day
Interval 1.1 to 2.0
|
1.6 mean stools per day
Interval 1.3 to 1.7
|
SECONDARY outcome
Timeframe: baseline and 3 - 5 months after cholecystectomySpearman correlation between change from baseline to after cholecystectomy in FGF19 and in mean number of stools
Outcome measures
| Measure |
Visit 1
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
Visit 2
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
|---|---|---|
|
Change in Stool Pattern Correlated to FGF19
|
-0.21 Spearman correlation coefficient
|
—
|
SECONDARY outcome
Timeframe: baseline and 3 - 5 months after cholecystectomyCorrelation between patient reported frequency of diarrhea (gastrointestinal quality of life index item 31) and fasting C4 before versus after cholecystectomy
Outcome measures
| Measure |
Visit 1
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
Visit 2
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
|---|---|---|
|
Change in Patient Reported Diarrhea Symptoms Correlated With Change in C4 From Baseline Before Versus After Cholecystectomy
|
-.23 Spearman correlation coefficient
|
-0.52 Spearman correlation coefficient
|
SECONDARY outcome
Timeframe: before cholecystectomy and 3-5 months after cholecystectomyChange in total AUC for C4 between visit 1 and visit 2
Outcome measures
| Measure |
Visit 1
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
Visit 2
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
|---|---|---|
|
Change in C4 Total Area Under the Curve From Baseline Before Versus After Cholecystectomy
|
774 ng/mL x minutes
Interval 524.0 to 1143.0
|
1040 ng/mL x minutes
Interval 765.0 to 1417.0
|
SECONDARY outcome
Timeframe: before and 3-5 months after cholecystectomychange in fasting FGF19 before versus after cholecystectomy
Outcome measures
| Measure |
Visit 1
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
Visit 2
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
|---|---|---|
|
Change in Fasting FGF19 From Baseline Before Versus After Cholecystectomy
|
102 pg per mL
Interval 74.0 to 141.0
|
92 pg per mL
Interval 67.0 to 125.0
|
SECONDARY outcome
Timeframe: baseline and 3 - 5 months after cholecystectomyCorrelation between patient reported frequency of diarrhea (gastrointestinal quality of life index item 31) and fasting FGF19 before versus after cholecystectomy
Outcome measures
| Measure |
Visit 1
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
Visit 2
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
|---|---|---|
|
Change in Patient Reported Diarrhea Symptoms Correlated With Change in FGF19 From Baseline Before Versus After Cholecystectomy
|
0.08 Spearman correlation coefficient
|
-0.07 Spearman correlation coefficient
|
SECONDARY outcome
Timeframe: baseline and 3 - 5 months after cholecystectomyChange 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.
Outcome measures
| Measure |
Visit 1
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
Visit 2
n=18 Participants
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
|---|---|---|
|
Change in Stool Consistency (Bristol Stool Type) From Baseline Before Versus After Cholecystectomy
|
4.2 Bristol stool type
Interval 3.7 to 4.8
|
4.0 Bristol stool type
Interval 3.6 to 4.5
|
Adverse Events
Visit 1
Serious events: 0 serious events
Other events: 22 other events
Deaths: 0 deaths
Visit 2
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Visit 1
n=22 participants at risk
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
Visit 2
n=18 participants at risk
chenodeoxycholic acid 1250mg po.
chenodeoxycholic acid: 1250 mg CDCA is given with a study meal
|
|---|---|---|
|
Nervous system disorders
Headache
|
4.5%
1/22 • Number of events 1 • 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).
|
0.00%
0/18 • 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).
|
|
Nervous system disorders
Migraine
|
4.5%
1/22 • Number of events 1 • 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).
|
0.00%
0/18 • 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).
|
|
Nervous system disorders
Dizzyness
|
4.5%
1/22 • Number of events 1 • 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).
|
0.00%
0/18 • 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).
|
|
General disorders
Fatigue
|
9.1%
2/22 • Number of events 2 • 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).
|
0.00%
0/18 • 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).
|
|
Gastrointestinal disorders
Abdominal bloating
|
4.5%
1/22 • Number of events 1 • 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).
|
5.6%
1/18 • Number of events 1 • 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).
|
|
Gastrointestinal disorders
Nausea
|
13.6%
3/22 • Number of events 3 • 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).
|
5.6%
1/18 • Number of events 1 • 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).
|
|
Gastrointestinal disorders
Diarrhea
|
63.6%
14/22 • Number of events 14 • 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).
|
77.8%
14/18 • Number of events 14 • 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).
|
|
Gastrointestinal disorders
Burping
|
4.5%
1/22 • Number of events 1 • 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).
|
0.00%
0/18 • 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).
|
|
Gastrointestinal disorders
Abdominal pain
|
13.6%
3/22 • Number of events 3 • 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).
|
27.8%
5/18 • Number of events 5 • 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).
|
|
Gastrointestinal disorders
Heartburn
|
4.5%
1/22 • Number of events 1 • 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).
|
5.6%
1/18 • Number of events 1 • 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).
|
|
General disorders
Malaise
|
4.5%
1/22 • Number of events 1 • 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).
|
0.00%
0/18 • 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).
|
|
Gastrointestinal disorders
Abdominal sounds/growling
|
22.7%
5/22 • Number of events 5 • 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).
|
11.1%
2/18 • Number of events 2 • 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).
|
Additional Information
Dr. Christian Borup, coordinating investigator
Zealand University Hospital
Phone: +4523328035
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place